2026 Spring Prime Therapeutics Report

Hereditary angioedema:

Recent approvals and payer management

Published By

Prime Therapeutics

2900 Ames Crossing Road Eagan, MN 55121 PrimeTherapeutics.com

Editor

Lindsay Speicher, J.D.

Sr. Project Manager, Specialty Lindsay.Speicher@PrimeTherapeutics.com

Advertising, Sales and Distribution

Lindsay Speicher, J.D.

Sr. Project Manager, Specialty Lindsay.Speicher@PrimeTherapeutics.com

Joe Tavares

SVP, Sales and Business Development, Specialty Joe.Tavares@PrimeTherapeutics.com

Contributors

Steve Cutts, PharmD SVP, Specialty and Clinical Solutions

Haita Makanji, PharmD VP, Clinical Strategy and Innovation, Specialty

Joe Tavares

SVP, Sales and Business Development, Specialty

Abby Kim, PharmD, BCOP Clinical Oncology Pharmacist Senior Principal

Shelae Cheng Marketing Principal, Brand Marketing Strategy

Brian MacDonald, PharmD Sr. Director, Specialty Clinical Strategy and Programs

Alina Young Sr. Legal Counsel

Editorial Advisory Board

Mona Chitre, PharmD Chief Pharmacy Officer, Lifetime Healthcare Companies

Dennis Bourdette, M.D., FAAN, FANA Chair and Roy and Eulalia Swank Family Research Professor, Department of Neurology, Oregon Health & Science University

Yousaf Ali, M.D., FACR Chief, Division of Rheumatology, Mount Sinai St. Luke's and Mount Sinai West Professor of Medicine, Icahn School of Medicine at Mount Sinai

Steven L. D’Amato, B.S.Pharm. Founding Partner, Scientia Pharmacy Advisors

Joseph Mikhael, M.D., M.Ed., FRCPC, FACP

Chief Medical Officer, International Myeloma Foundation

Steve Marciniak, RPh President, ClarityRX

Saira A. Jan, M.S., PharmD VP and Chief Pharmacy Officer, Horizon Blue Cross Blue Shield of New Jersey

A note from our SVP

Dear managed care colleagues,

Welcome to our spring 2026 issue of the Prime Therapeutics Report! There are many exciting advances anticipated throughout the year, with a robust pipeline across several categories. As always, Prime Therapeutics is dedicated to bringing our readers valuable updates in managed care trends.

This issue’s cover story (page 20) explores hereditary angioedema, specifically focusing on the evolving treatment landscape with new acute and prophylactic treatment options.

Another article (page 10) focuses on the always topical cell and gene therapy category. There are several new approvals in the category across indications. The article highlights epidermolysis bullosa and the new cell and gene therapy options for this rare disease.

In another article (page 26), we discuss myasthenia gravis and new targeted treatment alternatives.

This issue also includes a discussion of spinal muscular atrophy, a biosimilar update and the managed care newsstand. As always, we’ve rounded out this issue with the pipeline.

To learn more about how we’re supporting transformative payer initiatives, please feel free to contact us at PTReport@PrimeTherapeutics.com. As always, we value any feedback you may have. Enjoy the report!

Sincerely,

Steve Cutts, PharmD Senior Vice President, Specialty and Clinical Solutions Prime Therapeutics

Managed care newsstand

Executive action filled the policy gap

With limited legislative movement, the administration relied more heavily on executive authority and Centers for Medicare & Medicaid Services (CMS) Innovation Center models to advance drug pricing and access priorities, including most-favorednation (MFN)-style agreements and pricing demonstrations across Medicare and Medicaid.

GLP-1s stayed front and center

GLP-1 (glucagon-like peptide-1) agonist medications emerged as a dominant focus of federal policy activity and were increasingly framed as prevention tools. Federal actions emphasized negotiated pricing, clinical eligibility standards and demonstration-based access rather than immediate integration into standard benefit design.

Trump administration: MFN agreements, tariff leverage and direct-toconsumer update

In Q4, the administration moved forward with a series of voluntary, MFN-style pricing agreements with major pharmaceutical manufacturers, framing these deals as an alternative route to lower drug prices in the absence of congressional action. In November, several manufacturers,

including Lilly and Novo Nordisk, announced pricing commitments for GLP-1 therapies and agreed to offer products directly to consumers through the TrumpRx.gov platform, which launched in February.

Under this approach, cash-paying consumers will access MFN-based prices directly from manufacturers, outside traditional Medicare and commercial benefit structures. The administration described the platform as a way to bypass “middlemen.”

In December, nine additional manufacturers announced similar arrangements, committing to MFN-style pricing for future products, Medicaid price reductions and discounts for cash-paying consumers. In exchange, participating manufacturers would be exempt from proposed pharmaceutical tariffs ranging from 100% to 250%.

The durability of this strategy remains tied to the administration’s tariff authority. In November, the Supreme Court heard oral arguments challenging the president’s use of the International Emergency Economic Powers Act to impose sweeping tariffs. A ruling limiting that authority could reduce negotiating leverage, particularly with manufacturers that have not entered voluntary agreements.

Congressional oversight of these arrangements has already begun. Senate Finance Committee

Democrats requested additional information from participating manufacturers regarding the scope and implementation of their pricing commitments, signaling potential scrutiny of downstream impact.

While these agreements do not directly restructure PBM (pharmacy benefit manager) operations, they may influence manufacturer pricing behavior, rebate dynamics and plan bid assumptions. More broadly, they reinforce a continued shift toward executive-led pricing interventions operating alongside traditional coverage and benefit frameworks.

FDA accelerated review and downstream cost exposure

Congressional leaders raised concerns in Q4 about the U.S. Food and Drug Administration’s (FDA) National Priority Voucher pilot, pointing to potential risks related to transparency, regulatory integrity and patient safety. The pilot is a regulatory incentive program launched by the FDA in June 2025 and aims to accelerate the review of drugs and biologics that align with specific U.S. national health and security interests. More broadly, lawmakers continued to question accelerated approval pathways that can bring high-cost therapies to market earlier, often with limited clinical evidence and delayed competitive entry.

While FDA decisions occur upstream of coverage and benefit design, expedited approvals can shift clinical and financial risk downstream to plans and PBMs for extended periods. These dynamics can complicate utilization management, increase drug trend pressure and introduce volatility into bid development.

Forward-looking federal policy and regulatory considerations for 2026

Implementation and enforcement risk

PBM reform remains one of the most likely areas for congressional action in 2026. As Inflation Reduction Act (IRA) provisions mature, plans and PBMs should expect increased enforcement and operational scrutiny tied to implementation. This environment is further shaped by ongoing federal oversight activity, including the Federal Trade Commission’s pending final report on PBMs, which is expected to inform future enforcement and policy discussions.

ERISA transparency and employer oversight

The Department of Labor is expected to advance additional Employee Retirement Income Security Act (ERISA)-related transparency initiatives, including proposals focused on PBM fee and compensation disclosure in employer-sponsored plans. These efforts could influence employer expectations around PBM contracting, fiduciary responsibility and oversight. The Prime Government Affairs team is working closely with its trade association to engage in these proposals, particularly those focused on PBM transparency, and plans to

remain actively involved through the rulemaking and comment process as additional details emerge.

Drug pricing experimentation and IRA spillover

The first negotiated Medicare drug prices under the IRA will take effect in 2026, while multiple pricing initiatives, including GUARD, GLOBE, GENEROUS and BALANCE, move forward in parallel. The interaction between negotiated prices, ASP benchmarks, Medicaid reimbursement and safety-net access remains one of the most consequential and least predictable policy dynamics for plans and PBMs.

GLP-1 benefit management

GLP-1 therapies are shifting from policy debate to operational reality. Federal actions increasingly favor negotiated pricing, clinical eligibility criteria and demonstration-based access rather than immediate incorporation into standard benefit design, creating new utilization management and coordination challenges.

Medicaid volatility and statefederal tension

CMS guidance and state-level implementation decisions will continue to shape Medicaid eligibility, utilization and administrative complexity.

Supply chain and pharmacy access

Congressional attention to drug supply chain resilience, distributor practices and pharmacy access is expected to continue. At the same time, active state PBM legislation may inform or influence future federal policy approaches.

Federal regulations Medicare

CY 2027 policy and technical changes to MA and Part D proposed rule (CMS 4212-P)

CMS released the CY 2027 Medicare Advantage (MA) and Part D proposed rule, which largely focuses on refining and operationalizing provisions of the IRA rather than introducing new structural reforms. The proposal centers on stabilizing the redesigned Part D benefit, clarifying guidance related to negotiated pricing and beneficiary protections, and strengthening program integrity as IRA requirements continue to phase in.

Overall, the proposed rule reflects CMS’s effort to balance continued IRA implementation with growing attention to administrative burden and operational feasibility. Final policies will have implications for plan bids, operational readiness and longer-term Part D market stability.

Medicare drug negotiated prices for IPAY 2027

On Nov. 25, CMS released the Maximum Fair Prices that will apply to negotiated drugs beginning Jan. 1, 2027. The announced discounts for Medicare Part D drugs are substantial. Several GLP-1 therapies, including Ozempic, Rybelsus and Wegovy, received discounts of approximately 71% compared to 2024 list prices for a 30-day supply ($274 versus $959).

Barrett Duke, PharmD, MBA, CBA

Director of Pharmacy Services

HealthOne Alliance and Alliant Health Plans

Biosimilar update

Key approvals, launches and pipeline activity

As of February, 82 biosimilars have been approved by the U.S. Food and Drug Administration (FDA) across several unique molecules.1 Of those approved, 55 have been launched in the United States. Approved biosimilars cover several key therapeutic areas, such as oncology, ophthalmology and diabetes.1

2026 is poised to be an exciting year for continued expansion of the biosimilar landscape.

Launch of Eylea biosimilars

In November 2024, Pavblu (aflibercept-ayyh), the first biosimilar to Regeneron’s Eylea, launched after Amgen won a legal victory enabling the company to launch the only marketed Eylea biosimilar in the United States.2 In fall 2025, Regeneron settled a patent dispute with Celltrion, allowing another biosimilar to launch its aflibercept biosimilar, Eydenzelt, on Dec. 31, 2026.2 Sandoz, Formycon, Samsung Bioepis and Mylan Pharmaceuticals, along with the latter’s partner, Biocon Biologics, have also been subject to Regeneron’s attempt to block biosimilar competition in the courts.2 With this most recent settlement, competition will likely continue to intensify throughout 2026.2

Recent approvals Pertuzumab (Poherdy)

In November 2025, the FDA approved Poherdy (pertuzumab-dpzb) as the first interchangeable biosimilar to Perjeta.3 This marks the first approval of any biosimilar for Perjeta.3 Pertuzumab-dpzb is a HER2/neu receptor antagonist indicated for use in combination with trastuzumab and docetaxel for adults with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease; for use in combination with trastuzumab and chemotherapy as neoadjuvant treatment of adults with HER2-positive, locally advanced, inflammatory or early-stage breast cancer as part of

a complete treatment regimen for early breast cancer; or for adjuvant treatment of adults with HER2-positive early breast cancer at high risk of recurrence.3

The approval was based on a broad range of structural and functional product quality attributes, including those known to impact safety and efficacy, human pharmaco–kinetic (PK) data, clinical immunogenicity data and supportive clinical data in patients with breast cancer.3 This data supported Poherdy’s approval as an interchangeable biosimilar to Perjeta.3

The recommended initial dose for pertuzumab-dpzb is 840 mg administered as a 60-minute intravenous infusion, followed by a dose of 420 mg administered as an intravenous infusion over 30 to 60 minutes every three weeks.3 Poherdy comes with a boxed warning for left ventricular dysfunction and embryo-fetal toxicity, and warnings and precautions for infusion-related and hypersensitivity reactions or anaphylaxis.3

Denosumab (Osvyrti and Jubereq)

The FDA approved two new denosumab biosimilars in November 2025.4 Denosumab-desu (Osvyrti) and denosumab-desu (Jubereq) received approvals indicated for osteoporosis and cancer-related bone conditions,

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respectively.4 These mirror Prolia’s and Xgeva’s indications and mark the introduction of additional biosimilars in an ever-expanding denosumab landscape.4

Approvals were based on data from Phase 1 and Phase 3 trials for Jubereq and Osvyrti, respectively.4 In the Phase 1 randomized, double-blind, three-arm PK study, Jubereq was compared with Xgeva in healthy adult males, and results illustrated comparable PK parameters between the two.4 In the Phase 3 randomized, double-blind, activecontrolled, parallel-arm multicenter study, Osvyrti’s efficacy and safety were evaluated in comparison to Prolia’s in postmenopausal women with osteoporosis.4 Data from the trial demonstrated the two products were highly similar, with no clinically meaningful differences in terms of PK, pharmacodynamics, safety or efficacy.4

Omalizumab (Omlyclo)

In December 2025, the FDA approved omalizumab-igec (Omlyclo) 300 mg/2 mL solution as a single-dose prefilled syringe for subcutaneous injection, expanding dosing flexibility and supporting tailored treatments for individuals.5 Omalizumab-igec is the first and only biosimilar designated as interchangeable with Xolair.5 Previously, Omlyclo 75 mg/0.5 mL and 150 mg/mL in single-dose prefilled syringes for subcutaneous injection were

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Pipeline

Biosimilar (reference) Manufacturer

Interleukin inhibitors

secukinumab (BAT2306) Bio-Thera Solutions SC IL-17 antagonist Phase 3 Plaque psoriasis

secukinumab (CT-P55) Celltrion SC IL-17 antagonist Phase 3 Plaque psoriasis

mepolizumab (BAT2606) Bio-Thera Solutions SC

antagonist Phase 1 Severe asthma

tocilizumab (Tofidence SC) Bio-Thera Solutions SC IL-6R antagonist Phase 1 RA; JIA

Oncology

pertuzumab (EG1206A) EirGenix IV Anti-HER2 antibody Phase 3 HER2+ breast cancer

pertuzumab (PERT-IJS) Biocon IV Anti-HER2 antibody Phase 3 HER2+ breast cancer

trastuzumab (EG12014) Sandoz; EirGenix IV

trastuzumab (TX05) Tanvex IV

antibody Pending HER2+ breast cancer; gastroesophageal cancer; gastric cancer

antibody Pending (06/2026) HER2+ breast cancer; gastric cancer

trastuzumab (HD201) Han Wha Pharma; Prestige BioPharma IV Anti-HER2 antibody Phase 3 HER2+ breast cancer

bevacizumab (HLX04) Henlius IV VEGF inhibitor Pending (4Q 2026) HER2+ breast cancer

bevacizumab (FKB238) AstraZeneca; Fujifilm Kyowa Kirin; Centus Biotherapeutics IV VEGF inhibitor Pending NSCLC

bevacizumab (HD204) Prestige Biopharma IV

bevacizumab (TRS003) Zhejiang Teruisi Pharmaceutical IV

bevacizumab (Avbintio) Organon; Samsung Bioepis IV

pembrolizumab (HLX17) Henlius

pembrolizumab (CT-P51) Celltrion

pembrolizumab (SB27) Samsung Bioepis

pembrolizumab (ABP 234) Amgen

pembrolizumab (MB12) mAbxience; Fresenius Kabi

nivolumab (JPB898) Sandoz; Hexal

nivolumab (ABP 206) Amgen IV

nivolumab (MB11) mAbxience; Fresenius Kabi IV

inhibitor Phase 3 NSCLC; CRC

Biosimilar (reference) Manufacturer

daratumumab; TBD (CTP44 SC) Celltrion SC Anti-CD38 antibody Phase 3 MM

ipilimumab (HLX13) Henlius; Sandoz IV CTLA-4 inhibitor Phase 3 Liver cancer

filgrastim (Grastofil) Apotex; Accord; Intas IV; SC

pegfilgrastim (Lapelga) Apotex; Accord; Intas SC

Prolia/Xgeva

Colony-stimulating factor Pending

BMT; myelosuppressive chemotherapy; neutropenia; AML; peripheral blood progenitor cell collection and therapy

Colony-stimulating factor Pending Myelosuppressive chemotherapy

denosumab (TVB-009P) Teva Pharmaceuticals SC RANKL inhibitor Pending

denosumab (ENZ215)

Enzene Biosciences; Alkem Laboratories; Ascend SC RANKL inhibitor Pending (2Q 2026)

denosumab (Osqay) Enzene; Alkem Laboratories; Ascend SC RANKL inhibitor Pending (2Q 2026)

denosumab (LY01011)

Postmenopausal osteoporosis; osteoporosis in men

Hypercalcemia of malignancy; bone malignancy; bone metastases; giant cell tumor of bone

Increasing bone mass; postmenopausal osteoporosis; glucocorticoid-induced osteoporosis; osteoporosis in men

Nanjing Kingfriend Biochemical Pharmaceutical; Luye Pharma Group; Boan Biotech SC RANKL inhibitor Phase 3 Postmenopausal osteoporosis

denosumab (TVB-009X) Teva Pharmaceuticals SC RANKL inhibitor Phase 3 Postmenopausal osteoporosis

denosumab (EB1001) Eden Biologics SC RANKL inhibitor Phase 3 Postmenopausal osteoporosis

denosumab (LY06006) Luye Pharma Group; Boan Biotech SC RANKL inhibitor Phase 3 Postmenopausal osteoporosis

denosumab (BP16) CuraTeQ Biologics; Aurobindo Pharma SC RANKL inhibitor Phase 3 Postmenopausal osteoporosis

Ophthalmology

ranibizumab (LUBT010) Lupin Intravitreal VEGF inhibitor Pending (06/2026) Wet AMD

aflibercept (SCD411) Sam Chun Dang Pharm; Fresenius Kabi Intravitreal VEGF inhibitor Pending (10/2026) Wet AMD; DME; DR; macular edema following RVO

aflibercept (AVT06) Teva; Alvogen; Alvotech Intravitreal VEGF inhibitor Pending Wet AMD

aflibercept (RBS-001) Rophibio; Amicogen Intravitreal VEGF inhibitor Pending Wet AMD

Other

omalizumab (ADL-018) Kashiv BioSciences; Amneal Pharmaceuticals SC Anti-IgE antibody Pending (3Q 2026) CIU

Pipeline (cont.)

Biosimilar (reference) Manufacturer

omalizumab (TEV-45779) Teva SC Anti-IgE antibody Phase 3 CIU

omalizumab (BP11) Aurobindo; CuraTeQ SC Anti-IgE antibody Phase 3 CIU

golimumab (BAT2506) Bio-Thera Solutions; Intas Pharmaceuticals; Accord Healthcare SC

ocrelizumab (ABP 692) Amgen IV

ocrelizumab (CYB704) Sandoz IV

ocrelizumab (CT-P53) Celltrion IV

TNF-alpha inhibitor Pending (5/16/2026) AS; PsA; RA; UC

Anti-CD20 antibody Phase 3 RRMS

Anti-CD20 antibody Phase 3 RMS

Anti-CD20 antibody Phase 3 RRMS

vedolizumab (PB016) Polpharma; Fresenius Kabi IV Integrin receptor antagonist Phase 3 UC

abatacept (DRL_AB) Dr. Reddy’s Laboratories IV; SC

Immunosuppressant Phase 3 RA

infliximab (NI-071) Sagent Pharmaceuticals; Nichi-Iko; Aprogen IV TNF-alpha inhibitor Phase 3 RA

adalimumab (MYL-1401A) Mylan; Biocon SC TNF-alpha inhibitor Phase 3 JIA; plaque psoriasis; CD; AS; RA; PsA; HS; UC

etanercept (YLB113) Lupin SC TNF-alpha inhibitor Phase 3 RA

Abbreviations: AMD = age-related macular degeneration; AS = ankylosing spondylitis; BMT = bone marrow transplant; CD = Crohn’s disease; CIU = chronic idiopathic urticaria; CRC = colorectal cancer; DME = diabetic macular edema; DR = diabetic retinopathy; HS = hidradenitis suppurativa; IgE = immunoglobulin E; IL = interleukin; IV = intravenous; JIA = juvenile idiopathic arthritis; MM = multiple myeloma; NSCLC = non-small cell lung cancer; PD-1 = programmed cell death 1; PsA = psoriatic arthritis; RA = rheumatoid arthritis; RANKL = RANK ligand; RMS = relapsing multiple sclerosis; RRMS = relapsing-remitting multiple sclerosis; RVO = retinal vein occlusion; SC = subcutaneous; TNF = tumor necrosis factor; UC = ulcerative colitis; VEGF = vascular endothelial growth factor

approved by the FDA in March 2025.5 The biosimilar is anticipated to launch in September and create additional competition in the category as the first biosimilar for this reference product.

Payer management

According to data reported by the Association for Accessible Medicines, biosimilars have resulted in $36 billion in savings to patients and the health care system since 2015, including $12.4 billion in savings in 2023 alone.1 As of the end of 2024, biosimilars have occupied over 80% of the market share in drug categories covered under the medical benefit, especially bevacizumab, trastuzumab and pegfilgrastim.1 Uptake has been slower for drugs covered on the pharmacy benefit, such as adalimumab and insulin glargine.1

A 2025 payer survey provided insights into biosimilar coverage dynamics and strategies. A majority of payers have payment or coverage policies encouraging the use of biosimilars over reference products, and most payers reported preferring most or some biosimilars on their standard formularies.1 Notably, interchangeability designation does not necessarily impact decisionmaking, as over half of payers do not have policies that prefer interchangeable biosimilars.1 Over half of payers also reported they would cover a biosimilar for the same indications as the reference product, regardless of the approved indications or “skinny label.”1 Cost savings continue to be the driving factor in biosimilar adoption at most payer organizations (80%).1

Moving forward, this preference for biosimilars is anticipated to continue, and the landscape is expected to shift as biosimilars for new reference products emerge.

REFERENCES

1. Decoding biosimilar strategies: Key US payer trends for 2025. Cencora. Published August 2025. Accessed January 12, 2026. https://go.cencora.com/ cencora-content-biosimilar-whitepaper

2. Becker, Z. Regeneron settles Eylea patent dispute with Celltrion, allowing another biosimilar to launch at the end of 2026. Fierce Pharma. Published October 22, 2025. Accessed January 12, 2026. https://www.fiercepharma. com/pharma/regeneron-settles-eylea-patent-disputecelltrion-allowing-another-biosimilar-launch-2026

3. FDA approves new interchangeable biosimilar to Perjeta. U.S. Food and Drug Administration. Published November 13, 2025. Accessed January 4, 2026. https://www.fda. gov/drugs/resources-information-approved-drugs/ fda-approves-new-interchangeable-biosimilar-perjeta

4. Seymour, C. FDA approves Osvyrti and Jubereq in high fracture risk populations, including in breast and prostate cancer. OncLive. Published November 20, 2025. Accessed January 4, 2026. https://www.onclive.com/view/ fda-approves-osvyrti-and-jubereq-in-high-fracture-riskpopulations-including-in-breast-and-prostate-cancer

5. Celltrion announces U.S. FDA approval of 300 mg strength of OMLYCLO® (omalizumab-igec), the first and only FDA-approved interchangeable biosimilar to XOLAIR®. BioSpace. Published December 3, 2025. Accessed January 5, 2026. https://www.biospace.com/press-releases/ celltrion-announces-u-s-fda-approval-of-300mgstrength-of-omlyclo-omalizumab-igec-the-first-andonly-fda-approved-interchangeable-biosimilar-to-xolair

Gary Tereso, PharmD, RPh

Director of Pharmacy

Health

New England

Cell and gene therapy

Expanding pipeline and strategic approaches

Thousands of gene and cell therapy candidates are in various stages of development, and the U.S. Food and Drug Administration (FDA) is slated to potentially approve dozens over the next few years. As of the Q3 2025 edition of the Gene, Cell & RNA Therapy Landscape Report from the American Society of Gene + Cell Therapy, there were 4,341 identified therapies in development across the pipeline, ranging from preclinical through preregistration; gene therapies accounted for 49% of all cell, gene and RNA therapeutics in development.1 Recent trial initiations suggest increasing development outside of oncology, with 51% of newly initiated gene therapy trials targeting conditions other than cancer.1

While cell and gene therapies represent exciting and promising new opportunities for potentially curative treatment, they are also some of the world’s most expensive drugs. These high price tags can be attributed to high manufacturing costs, use of advanced technologies and relatively small target populations. This is in contrast with biologics, which prove expensive due to ongoing treatment costs.

Recent approvals

Zopapogene imadenovec-drba (Papzimeos)

In August 2025, the FDA approved zopapogene imadenovec-drba (Papzimeos).2 This therapy is a first-of-its-kind, nonreplicating, adenoviral, vector-based immunotherapy indicated for the treatment of adult patients with recurrent respiratory papillomatosis (RRP).2 This novel therapy triggers an immune response against cells infected with

human papillomavirus (HPV) types 6 and 11, which cause RRP.2 Zopapogene imadenovec is administered via four subcutaneous injections over the course of three months, providing patients with durable reduction in disease burden, as measured by decreased need for surgery.2

Results from a single-arm, open-label trial evaluating zopapogene imadenovec in adult patients with RRP who required three or more surgeries per year showed that 51.4% of patients achieved a complete response, meaning they did not need a surgical procedure in the 12 months following treatment.3 Data showed that 15 of the 18 patients who achieved a complete response maintained it for two years, and patients in the trial averaged 0.5 surgeries in the year following treatment.3

Most treatment-emergent adverse events were mild to moderate, and no dose-limiting toxicities were observed or treatment-related serious adverse events reported.2

The pricing of zopapogene imadenovec is estimated at $300,000 to $500,000 per treatment.

Revakinagene taroretcel (Encelto)

In March 2025, the FDA approved revakinagene taroretcel (Encelto) as the first treatment to slow or stop vision loss in those diagnosed with macular telangiectasia

These high price tags can be attributed to high manufacturing costs, use of advanced technologies and relatively small target populations.

type 2 (MacTel).4 Revakinagene taroretcel is a surgically implanted device designed to preserve sight in those with this condition.4 Data from two Phase 3 clinical studies supported the approval. Results of these studies showed that the implant slowed the loss of light-sensing retinal cells in people with MacTel over a 24-month period. When devices were removed from patients’ eyes after as long as 14.5 years, they still produced levels of ciliary neurotrophic factor (CNTF) comparable to initial output.4

The pricing of revakinagene taroretcel is estimated at $200,000 to $440,000 per treatment.

Onasemnogene abeparvovec (Itvisma)

The FDA approved onasemnogene abeparvovec (Itvisma) in November 2025 for the treatment of spinal muscular atrophy (SMA) in adult and pediatric patients age 2 and older with confirmed mutation in the survival motor neuron 1 (SMN1) gene.5 This adeno-associated virus (AAV) vector-based gene therapy contains the same active ingredient as Zolgensma, but it is formulated at a different concentration.5 While Zolgensma is administered intravenously based on patient weight, Itvisma is a concentrated formulation in a smaller delivery volume, administered directly to the central nervous system via a single intrathecal injection independent of patient weight, expanding treatment options available to patients older than age

The FDA’s approval decision incorporated clinical trial results in pediatric patients 2 years of age and older with a confirmed mutation in the SMN1 gene, as well as mechanistic and comparative evidence supporting efficacy across broader age groups.5

Intrathecal administration of Itvisma allows for direct delivery to motor neurons with a lower dose of vector, providing a treatment with rapid onset and direct targeting of the genetic root cause of SMA.5

The estimated price of onasemnogene abeparvovec is $2.59 million per treatment.

Etuvetidigene autotemcel (Waskyra)

In December 2025, the FDA approved etuvetidigene autotemcel (Waskyra) as the first cell-based gene therapy for the treatment of Wiskott-Aldrich syndrome (WAS).6 This therapy is indicated for pediatric patients age 6 months and older; and for adults with WAS who have a mutation in the WAS gene and for whom hematopoietic stem cell transplantation (HSCT) is appropriate and no suitable human leukocyte antigen (HLA)-matched related stem cell donor is available.6

Approval was based on safety and effectiveness data from two open-label, single-arm, multinational clinical studies and an expanded access program totaling 27 patients with severe WAS.7 These studies and program demonstrated etuvetidigene autotemcel’s substantial and sustained clinical benefit for patients with severe WAS, finding significant reductions in primary disease

manifestations that drive morbidity and mortality.7,8 In the 6 to 18 months post-treatment period, the rate of severe infections decreased by 93% compared to the rate 12 months before treatment.7,8 Moderate and severe bleeding events were similarly reduced by 60% in the first 12 months post-treatment compared to the year prior to treatment.7,8 In most patients, no moderate to severe bleeding was reported after four years post-treatment.7,8

The estimated price of etuvetidigene autotemcel is $3.25 million per treatment.

Prademagene zamikeracel (Zevaskyn)

In April 2025, the FDA approved prademagene zamikeracel (Zevaskyn) for the treatment of wounds in adult and pediatric patients with recessive dystrophic epidermolysis bullosa (RDEB).9 Prademagene zamikeracel (pz-cel), a gene-modified cellular sheet therapy, is the first and only autologous cell-based gene therapy with this indication.9

Results from the pivotal Phase 3 VIITAL study, a multicenter, randomized, intrapatient-controlled trial, informed the approval.10 The trial met its two co-primary efficacy endpoints by demonstrating statistically significant healing of 50% or more from baseline in large chronic

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RDEB wounds and pain reduction from baseline as assessed by the Wong-Baker FACES scale, as evaluated at six months after treatment.10 A total of 43 large and chronic wounds were treated with a single application of pz-cel, and 81% of wounds showed 50% or more healing compared to 16% in 43 matched control wounds treated with standard of care.10

In the single-center, open-label Phase 1/2a pz-cel study, 38 chronic wounds across 78 patients that showed a single surgical application of pz-cel was associated with long-term improvement at treated sites over a median follow-up of 6.9 years, over a range of 4 to 8 years.11

Pz-cel was well tolerated across both clinical studies with no treatment-related serious adverse events observed to date. Most common adverse events were observed in fewer than 5% of patients and included procedural pain and itch.10,11 The cost for this potentially life-changing treatment is $3.1 million for every 12 cellular sheets produced.12

Lisocabtagene maraleucel (Breyanzi)

In December 2025, the FDA approved lisocabtagene maraleucel (Breyanzi) for the treatment of adults with relapsed or refractory marginal zone lymphoma (MZL) who have received at least two prior lines of systemic therapy.13 Approval was based on efficacy results from the TRANSCEND FL-MZL Cohort, an open-label, multicenter, single-arm trial in adults with relapsed or refractory MZL who had received at least two or more lines of systemic therapy or who relapsed after hematopoietic stem cell transplant (HSCT), with an ECOG performance of one or less.13

Patients in the trial received a single dose of lisocabtagene maraleucel two to seven days following the completion of lymphodepleting chemotherapy.14 Overall response rate (ORR) was defined as the percentage of patients with the best overall response (BOR) of complete response (CR) or partial response (PR) per Lugano criteria and duration of response (DOR).14 In the intention-to-treat population, ORR was 84.4% and CRR was 55.8%.14 Median DOR was not reached.14

Prescribing information for lisocabtagene maraleucel includes warnings and precautions for cytokine release syndrome (CRS), neurologic toxicities, hypersensitivity reactions, serious infections, prolonged cytopenias, hypogammaglobulinemia, secondary malignancies, and immune effector-cell-associated hemophagocytic lymphohistiocytosis-like syndrome.13 Recommended dose

is 90-110 x 106 CAR-positive viable T cells with a 1:1 ratio of CD4 and CD8 components.13

The estimated price of lisocabtagene maraleucel is $410,300.

Payer management

Epidermolysis bullosa

The cost of treating epidermolysis bullosa (EB) long term can be burdensome to patients and payers alike. In a survey of EB patients and caregivers published in 2020, respondents with recessive dystrophic EB (RDEB) and junctional EB reported a major or moderate financial impact, with 26% reporting spending greater than $1,000 per month in wound care supplies alone.15 Findings of an analysis of hospitalization costs associated with pediatric EB patients showed that inpatient admissions were significantly more expensive than outpatient management of EB patients. On average, these patients were admitted for 9.2 days and charged $112,500. The greatest charges were demonstrated among patients with dystrophic EB.16

Adding an additional gene therapy option to the treatment landscape for EB will undoubtedly create an imminent need for effective payer-management strategies. Notably, these topical cellular treatments offer a reduction in chronic wound progression that would reduce

complications that may lead to early mortality in RDEB patients, especially infection, sepsis and the development of squamous cell carcinoma. However, not a single available therapy addresses the underlying gene mutation that causes the disorder.

Some options for coverage and cost-mitigation strategies include utilization management, reimbursement strategies and evaluating care management programs. Payers will want to explore potential reimbursement strategies, in the form of value-based outcome programs, that are available for these cellular or gene therapies. Identifying outliers via claims monitoring processes can also help protect payers from unexpected high-cost reimbursements.

Management strategies

Pharmacy and overall health care expenditures in the United States are rising at rates that are increasingly unsustainable for employers, government programs and health plans. Specialty drugs already account for a disproportionate share of total spend, and the accelerating pipeline of high-cost gene and cell therapies—often priced in the hundreds of thousands to millions per treatment— will further intensify financial pressures. Given these high costs and the challenges already faced by the health care system, it may be necessary to implement innovative solutions as the category continues to expand. High costs

will trigger an increased focus on outcomes via valuebased purchasing and contracting. Without structural reforms in pricing, payment models and value assessment, payers will face mounting affordability challenges that threaten long-term system stability.

Within value-based purchasing are two distinct concepts.17 First, value-based contracting is performancebased contracting among payer, provider or manufacturer stakeholders in which reimbursement is tied to patient health measures and other real-world outcomes and costs for a defined period of time.17 Alternative payment contracting as a payment approach centers on providing predictable costs, and it ties payment to provider or therapy performance over a defined period of time.17 Exploring innovative payment models will be key to effectively strategizing payment in this category.18

Outcomes-based contracts are focused on agreed-upon clinical outcomes between the product manufacturer and the payer.18 The manufacturer and payer may agree upon additional payments for clinical outcomes met or financial rebates for clinical outcomes not achieved.18 The outcomes can be measured at the individual patient level or for a population, and can be captured in routine care or collected via claims data.18 A new Medicaid test program covering new gene-based sickle cell disease treatments, initially proposed by the Biden administration, has been continued by the Trump administration; 33 states, along with D.C. and Puerto Rico, will participate in the Cell and Gene Therapy Access model. The Centers for Medicare & Medicaid Services (CMS) has negotiated outcomes-based agreements for gene therapies for sickle cell disease with both Vertex, manufacturer of exagamglogene autotemcel (Casgevy), and Bluebird Bio, manufacturer of lovotibeglogene autotemcel (Lyfgenia).18

Under risk-based contracts, payment is linked to the distribution of risk for the specified treatment or medical intervention.17 This can be done by measuring financial performance, medication utilization or health outcomes.17 These contracts are similar to outcomes-based contracts in that they are advantageous when treatment outcomes are uncertain or hard to measure. However, risk-based contracts place a greater focus on financial performance and are defined by their reliance on expected real-world outcomes and the expectation that treatment responses may vary.17 These contracts may include upside (additional payments if metrics or savings are achieved) or downside (penalties if metrics are not met).17

Alternative payment models include annuity payments over time, which can be combined with annuity outcomes

Rare diseases

mozafancogene autotemcel (RP-L102)

pariglasgene brecaparvovec (DTX401)

giroctocogene fitalparvovec (SB-525) Sangamo

dabocemagene autoficel (D-Fi)

onasemnogene abeparvovec (Zolgensma IT)

nexiguran ziclumeran (NTLA-2001) Intellia Therapeutics; Regeneron

rivunatpagene miziparvovec (UX701)

lenadogene

(GS010)

botaretigene sparoparvovec (AAV-RPGR)

laruparetigene zovaparvovec (AGTC-501)

beremagene geperpavec (KB803)

descartes-08

avalotcagene ontaparvovec (DTX301)

olenasufligene relduparvovec (LYS-SAF302)

Johnson & Johnson Innovative

Drug Manufacturer

(SRP-9003)

Common diseases

axicabtagene ciloleucel (Yescarta) Kite

alferminogene tadenovec (Generx)

ixoberogene soroparvovec (ADVM-022)

surabgene lomparvovec (RGX-314)

tonogenchoncel-L (Invossa)

donaperminogene seltoplasmid (Engensis)

lisocabtagene maraleucel (Breyanzi)

anitocabtagene autoleucel (KITE-772) Arcellx; Kite Pharma

arlocabtagene autoleucel (BMS-986393) Bristol-Myers Squibb

nadofaragene firadenovec (Adstiladrin) FKD Therapies; Ferring Pharmaceuticals

aglatimagene besadenovec (CAN 2409) Candel Therapeutics Injectable Immunomodulators Prostate cancer Phase 3 IMA203 Immatics IV

Abbreviations: ATTR-CM = transthyretin amyloid cardiomyopathy; CAR T = chimeric antigen receptor T cell; CRISPR = Clustered Regularly Interspaced Short Palindromic Repeats; DMD = Duchenne muscular dystrophy; FAP = familial amyloid polyneuropathy; HAE = hereditary angioedema; IM = intramuscular; IV = intravenous; LGMD = limb-girdle muscular dystrophy; LHON = Leber’s hereditary optic neuropathy; MM = multiple myeloma; MZL = marginal zone lymphoma; OA = osteoarthritis; PTLD = post-transplant lymphoproliferative disorder; SMA = spinal muscular atrophy; UTI = urinary tract infection; wAMD = wet age-related macular degeneration

contract terms, in which payments can stop if the gene therapy fails to deliver continued effectiveness or results in negative safety outcomes. These models have been

Including patient interests and ensuring access considerations are also key to gene therapy payment and valuebased contracting considerations.

popular ideas for gene therapies; however, annuitybased installment payments have not been adopted due to challenges with ensuring the payments can be transferred from one insurer to another if the individual changes insurance.

As with the operational challenges with annuities, warranties may not be feasible for some gene therapies because the treatment costs prior to gene therapy are minimal in comparison to the gene therapy cost itself. However, when the current disease therapy costs are well-defined or the future disease costs can be identified, gene therapy warranties hold promise. Hemophilia gene therapy manufacturers CSL Behring and BioMarin offer warranties for their products, while Novartis offers an annuity payment model for Zolgensma.19

Crucial to the effectiveness of these contracts is clearly defining what it means for the treatment to work or stop working.18 Additionally, it will be critical to partner with a health plan or pharmacy benefit manager who has the data and can fulfill the warranty, annuity, risk-based or outcomes contract reporting terms.

Other payment approaches include price volume and expenditure caps.18 Price-volume models decrease the price per unit as the sales of therapy increase. With expenditure-cap models, however, the price per unit stays the same until a spending limit is reached, after which there is no charge for additional units.18

Subscription payment models are sometimes considered a version of an expenditure model, in which payers have access to an unlimited supply of a gene therapy in exchange for a set fee. These models tend to work best when the marginal cost of production for therapy is low, which is not yet the reality for cell and gene therapies.18

Alternative payment models are critical to financing and ensuring access to these therapies when appropriate. Including patient interests and ensuring access considerations are also key to gene therapy payment and value-based contracting considerations; for further details, please refer to the Prime Therapeutics and Eli Lilly white paper.20

As these payment models and value-based contract terms are developed, utilized and assessed, ongoing concerns continue to arise, such as the burden of information tracking, regulatory barriers, pricing and reporting requirements. Manufacturers and payers alike will have to collaborate to develop creative outcomes assessment terms and payment models that will allow access while easing the financial burdens associated with these treatments.

REFERENCES

1. Gene, Cell, & RNA Therapy Landscape Report. American Society of Gene & Cell Therapy. Published November 2025. Accessed January 12, 2026. https://www.asgct.org/ uploads/files/general/Landscape-Report-2025-Q3.pdf

2. Dunleavy, K. Precigen scores FDA nod for first-ever treatment for HPV-related disorder. Fierce Pharma. Published August 15, 2025. Accessed September 24, 2025. https://www.fiercepharma.com/pharma/precigen-scoresfda-nod-first-ever-treatment-hpv-related-disorder

3. Norberg, SM, Valdez J, Napier S, et al. PRGN-2012 gene therapy in adults with recurrent respiratory papillomatosis: a pivotal phase 1/2 clinical trial. Lancet Respir Med. 2025;13(4):318–326. doi: 10.1016/ S2213-2600(24)00368-0

4. FDA approves ENCELTO, a first-of-its-kind eye implant that slows vision loss in rare eye disease. Scripps Research. Published June 4, 2025. Accessed November 4, 2025. https://www.scripps.edu/news-and-events/pressroom/2025/20250604-friedlander-encelnto.html

5. FDA approves gene therapy for treatment of spinal muscular atrophy. U.S. Food and Drug Administration. Published November 24, 2025. Accessed December 3, 2025. https://www.fda.gov/news-events/ press-announcements/fda-approves-gene-therapytreatment-spinal-muscular-atrophy

6. FDA approves first gene therapy treatment for Wiskott-Aldrich Syndrome. U.S. Food and Drug Administration. Published December 9, 2025. Accessed January 12, 2026. https://www.fda.gov/news-events/ press-announcements/fda-approves-first-genetherapy-treatment-wiskott-aldrich-syndrome

7. Ferrua, F, Cenciarelli S, Giannelli S, et al. Lentiviral hematopoietic stem and progenitor cell gene therapy with Etuvetidigene autotemcel for the treatment of WiskottAldrich Syndrome. Blood. 2025;146(Supplement1):6092. doi: 10.1182/blood-2025-6092

8. Ferrua, F, Cenciarelli S, Giannelli S, et al. Etuvetidigene autotemcel for the treatment of Wiskott-Aldrich Syndrome. MedRxiv. 2025. doi: 10.64898/2025.11.25.25340584

9. U.S. FDA approves ZEVASKYN™ (prademagene zamikeracel), the first and only cell-based gene therapy for patients with recessive dystrophic epidermolysis bullosa (RDEB). Abeona Therapeutics. Published April 29, 2025. Accessed October 2, 2025. https://investors. abeonatherapeutics.com/press-releases/detail/303/u-sfda-approves-zevaskyn-prademagene-zamikeracel

10. Tang, JY, Marinkovich MP, Wiss K, et al. Prademagene zamikeracel for recessive dystrophic epidermolysis bullosa wounds (VIITAL): a two-centre, randomised, open-label, intrapatient-controlled phase 3 trial. Lancet. 2025;406(10499):163–173. doi: 10.1016/ S0140-6736(25)00778-0

11. Multi-million dollar gene therapy ZEVASKYN™ increases health care cost in rare skin disorder - recessive dystrophic epidermolysis bullosa. PSG. Published June 11, 2025. Accessed November 19, 2025. https://www. psgconsults.com/blog/multi-million-dollar-gene-therapyzevaskyn-increases-health-care-cost-in-rare-skindisorder-recessive-dystrophic-epidermolysis-bullosa/

REFERENCES

12. Gorell, ES, Wolstencroft PW, De Souza, M, Murrell DF, Linos E, Tang JY. Financial burden of epidermolysis bullosa on patients in the United States. Pediatr Dermatol 2020;37(6):1198–1201. doi: 10.1111/pde.14340

13. FDA approves lisocabtagene maraleucel for relapsed or refractory marginal zone lymphoma. U.S. Food and Drug Administration. Published December 4, 2025. Accessed February 16, 2026. https://www.fda.gov/ drugs/resources-information-approved-drugs/ fda-approves-lisocabtagene-maraleucel-relapsed-orrefractory-marginal-zone-lymphoma#:~:text=On%20 December%204%2C%202025%2C%20the%20Food%20 and%20Drug,at%20least%20two%20prior%20lines%20 of%20systemic%20therapy.

14. Palomba, M.L., et al. Lisocabtagene maraleucel in patients with relapsed or refractory marginal zone lymphoma (TRANSCEND FL): primary analysis results from the global, multicohort, single-arm, phase 2 study. Lancet. 2026. doi:10.1016/S0140-6736(25)02435-3

15. Desai, AD, Singal A, Behbahani S, Soliman Y, Hawryluk EB. Cost of hospitalization for care of children with epidermolysis bullosa in the U.S. JAAD. Published July 2020. Accessed January 29, 2026. https://www.jaad.org/ article/S0190-9622(24)00479-1/fulltext

16. In the world of value-based care, words matter. Academy of Managed Care Pharmacy. Published August 2022. Accessed January 29, 2026. amcp.org/sites/default/ files/2022-08/VBCLexicon_0726.pdf

17. Wehrwein, P. They cost millions. How payers might manage those astronomical gene therapy bills. Managed Healthcare Executive. Published November 28, 2023. Accessed January 12, 2026. managedhealthcareexecutive. com/view/they-cost-millions-how-payers-mightmanage-their-gene-therapy-bills

18. Hagen, T. Gene therapy performance guarantees will ‘improve access’.’ Managed Healthcare Executive. Published August 17, 2023. Accessed January 12, 2026. managedhealthcareexecutive.com/view/gene-therapyperformance-guarantees-will-improve-access-

19. Hixson M, Minkoff NB, Gwiazdzinski K, Clement J. The impact of reinsurance of gene therapies on employer financial risk. Am J Manag Care. 2021;27(3 Spec No.):SP112-SP115. doi:10.37765/ajmc.2021.88653

20. Advancing patient interests through value-based arrangements for prescription drugs. Prime Therapeutics and Eli Lilly. Published September 2021. Accessed January 12, 2026. https://www.primetherapeutics.com/ wp-content/uploads/2021/09/document-eli-lily-whitepaper-value-based-arrangements.pdf

Mark Lorson, PharmD, MBA, BCACP, BCGP

Vice President, Pharmacy

Neighborhood Health Plan of Rhode Island

Hereditary angioedema

Recent approvals and payer management

Hereditary angioedema (HAE) is a rare condition that causes recurrent episodes or attacks of severe swelling of the skin and mucous membranes, most often affecting the face, hands, arms, legs, genitals and buttocks.1 Upper airway swelling is less common but more dangerous and can cause complete airway obstruction.1 While the skin swelling can cause pain, dysfunction and disfigurement, it is not considered dangerous.1 Attacks can affect one or more areas of the body, and symptoms depend on the organs impacted by the swelling.1 For example, gastrointestinal tract swelling can cause nausea, vomiting, diarrhea and abdominal pain.1

There are three types of HAE, which together affect about 1 in 50,000 people worldwide.2,3 Type I is the most common form and occurs when the body does not produce enough C1 esterase inhibitor (C1-INH), a protein that helps regulate inflammation and prevent excessive swelling. Type II occurs when C1-INH is present but does not function properly. Type III, also known as HAE with normal C1-INH, involves normal levels of the protein but swelling still occurs due to other genetic factors.2,3

HAE is primarily caused by genetic changes in the SERPING1 gene (the gene responsible for producing C1-INH) or, in some cases, mutations in the F12 gene.2,3 These mutations lead to abnormal regulation of inflammation pathways, resulting in recurrent swelling episodes. In a portion of patients, the exact genetic cause remains unknown. HAE follows an autosomal dominant inheritance pattern, meaning a person only needs one altered gene to be affected. However, not everyone who inherits a mutation will develop symptoms.2,3

While HAE’s clinical presentation varies, it usually presents with nonpitting angioedema and abdominal pain.1,2 Symptoms of HAE may appear at any time in life, though young patients’ symptoms may not be recognized until they worsen at puberty.1-3 HAE attacks typically last 2–5 days and can be hard to predict.2,3 Attacks may have varying triggers, but common attack triggers include emotional stress, physical stress, infection and dental procedures.1,2

Diagnosis

Diagnosis time is critical in HAE cases, as late or inaccurate diagnosis can lead to difficulties, such as subcutaneous or submucosal nonpitting angioedema.3 As many primary care providers (PCPs) may not be familiar with rare disease, it can take more than six years to receive an accurate diagnosis, delaying initiation of effective care.1,2 A physical exam should be performed to rule out allergic angioedema.3 Blood tests should also be performed to evaluate C1-INH levels and function, and, in some cases, genetic testing can be used to look for mutations that can cause HAE.3

Treatment landscape

Proper HAE management includes both on-demand medications for acute attacks and prophylactic or preventive medications.4 The main goal of acute, on-demand therapies is to rapidly relieve acute symptoms to minimize morbidity and mortality.4 Meanwhile, prophylactic strategies work to reduce attack frequency and improve patient autonomy and quality of life.4

Emerging therapies promise to evolve the landscape and may potentially simplify treatment and personalize care.

Emerging therapies promise to evolve the landscape and may potentially simplify treatment and personalize care.4 Some of these emerging therapies include novel oral agents, monoclonal antibodies, RNA therapies and gene editing approaches.4 This expanding pipeline collectively aims to address unmet needs and gaps in care while providing broader accessibility and convenience for HAE care and management.4

Recent approvals

Garadacimab-gxii (Andembry)

The U.S. Food and Drug Administration (FDA) approved garadacimab-gxii (Andembry) in June 2025 for the prophylactic treatment of HAE in patients 2 years and older.5 Garadacimab is a monoclonal antibody designed to block the activated form of the plasma protein factor XII (FXIIa).5 This marks the first and only approval for a treatment targeting FXIIa, a key initiator of the biological cascade that causes swelling attacks in people with HAE.5 Approval was based on results from the Phase 3 VANGUARD trial, which demonstrated garadacimab’s efficacy.5 Results showed 62% of patients on garadacimab experienced no attacks during the treatment period, and

the median attack reduction was more than 99%.6 The number of attacks requiring on-demand therapy and the number of moderate or severe attacks were reduced by approximately 88% and 90%, respectively.6

The most common side effects associated with garadacimab were nasopharyngitis and abdominal pain.5 The recommended dose for garadacimab is 400 mg as a loading dose, followed by a monthly maintenance dose of 200 mg.5

Sebetralstat (Ekterly)

In July 2025, the FDA approved sebetralstat (Ekterly) as a new, oral treatment for acute HAE attacks in adults and children age 12 and older.7

Results from the Phase 3 KONFIDENT trial revealed that sebetralstat demonstrated swifter symptom relief and attack resolution, as well as reduction in attack severity, compared to the placebo.8 Additionally, sebetralstat was well-tolerated and had a safety profile consistent with the placebo.8 Data from the KONFIDENT-S extension study showed that patients on sebetralstat experienced symptom relief in a median of 1.3 hours for attacks involving the larynx or abdomen, and for breakthrough attacks in patients receiving long-term preventive treatment.8

Prior to this approval, on-demand treatment of acute HAE attacks required administration via subcutaneous injection or intravenously, delaying an already timesensitive intervention.7 This simplified oral dosing of on-demand therapy has the potential to change the HAE treatment landscape.7

Donidalorsen (Dawnzera)

Donidalorsen (Dawnzera) received FDA approval in August 2025 as the first and only RNA-targeted prophylactic HAE treatment in adult and pediatric patients 12 years of age and older.9 Donidalorsen is self-administered via subcutaneous autoinjector once every four (Q4W) or every eight weeks (Q8W).9 Results from the Phase 3 global, multicenter, randomized, double-blind, placebocontrolled OASIS-HAE study demonstrated improvement in quality of life and other positive outcomes.9 In the study, donidalorsen Q4W significantly reduced the monthly HAE attack rate by 81% compared to the placebo over 24 weeks.10 When measured from the second dose, the mean

attack rate reduced by 87%.10 Donidalorsen Q4W reduced moderate to severe HAE attacks by around 90% over 24 weeks when measured from the second dose.10

The ongoing OASISplus open-label extension study shows donidalorsen Q8W had similar outcomes to Q4W over time, with donidalorsen demonstrating 94% total mean attack rate reduction from baseline across both dosing groups after one year.11 In the OASISplus study, a

This simplified oral dosing of on-demand therapy has the potential to change the HAE treatment landscape.

switch cohort evaluated donidalorsen Q4W in patients previously treated with lanadelumab, C1 esterase inhibitor or berotralstat for at least 12 weeks.11 In that cohort, switching to donidalorsen reduced mean HAE attacks by 62% from prior prophylactic treatment over 16 weeks, with no mean increase in breakthrough attacks.11 When surveyed, 84% of patients preferred donidalorsen over their prior prophylactic treatment, noting better disease control, shorter administration time, less injection site pain or fewer reactions.11

The most common adverse effects associated with donidalorsen were injection site reactions, upper respiratory tract infection, urinary tract infection and abdominal discomfort.

Berotralstat (Orladeyo)

In December 2025, the FDA approved the oral pellet formulation of once-daily berotralstat (Orladeyo) for prophylactic therapy in pediatric patients with HAE age 2 to 12.12 Previously, a capsule formulation of the drug was approved for prophylactic use in those with HAE age 12 and older.12

Positive interim data from the APeX-P clinical trial supported approval.13 The trial aims to describe the pharmacokinetic (PK) parameters of berotralstat and assess the safety and tolerability in pediatric patients with HAE.11 Interim results showed berotralstat was well-tolerated and demonstrated a consistent safety profile across the age group.13

Berotralstat was associated with early and sustained reductions in monthly attack rates with no new safety signals beyond those previously described in prior adult and adolescent trials.13 Nasopharyngitis was the mostreported treatment-emergent adverse event.13

The new pellet formulation can be poured directly into the mouth and swallowed immediately with water or milk, or sprinkled over a spoonful of soft, nonacidic food.12

Payer management

HAE therapies are covered under both the pharmacy and medical benefit.14 Self-administered drugs are typically covered under the pharmacy benefit.14 Drugs for this indication are typically covered with prior authorization (PA). Once PA is defined, diagnosis is confirmed by C4 and C1-INH levels below normal, and a history of HAE attacks is required.14 More than 63% of the covered lives in commercial lines of business have utilization management restrictions on HAE medications, and around half of Medicare beneficiaries are not covered for at least one of the HAE drugs.14 Under the medical benefit, more than 50% of commercial and exchange lives are covered, with management restrictions, while only 13% of Medicare beneficiaries have such restrictions in place.14

REFERENCES

1. Hereditary angioedema. National Institutes of Health. Published August 2025. Accessed September 23, 2025. https://rarediseases.info.nih.gov/diseases/5979/ hereditary-angioedema

2. Sinnathamby ES, et al. Hereditary angioedema: Diagnosis, clinical implications, and pathophysiology. Adv Ther 2023;40(3): 814–827. doi:10.1007/s12325-022-02401-0

3. Hereditary angioedema. Cleveland Clinic. Accessed January 12, 2026. https://my.clevelandclinic.org/health/ diseases/hereditary-angioedema#diagnosis-and-tests

4. Uminski K, et al. Therapeutic advances in hereditary angioedema: A focus on present and future options. Adv Ther. 2025;42(12):5879-5895. doi:10.1007/ s12325-025-03382-6

5. Lutton L. FDA approves hereditary angioedema therapy, Andembry. Managed Healthcare Executive. Published June 18, 2025. Accessed January 28, 2026. https://www. managedhealthcareexecutive.com/view/fda-approveshereditary-angioedema-therapy-andembry

6. Craig TJ, et al. Efficacy and safety of garadacimab, a factor XIIa inhibitor for hereditary angioedema prevention (VANGUARD): a global, multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet. 2023;401(10382):1079-1090. doi:10.1016/ S0140-6736(23)00350-1.

7. Kansteiner F. KalVista bounces back from FDA delay with approval for oral rare disease med Ekterly. FiercePharma. Published July 7, 2025. Accessed September 9, 2025. https://www.fiercepharma.com/pharma/ kalvista-bounces-back-delay-fda-approval-oral-raredisease-med-ekterly

8. Riedl MA, et al. Oral sebetralstat for on-demand treatment of hereditary angioedema attacks. New Eng J Med 2024;391:32–43. doi:10.1056/NEJMoa2314192

9. DAWNZERA™ (donidalorsen) approved in the US as first and only RNA-targeted prophylactic treatment for hereditary angioedema. Ionis Pharmaceuticals, Inc. Published August 21, 2025. Accessed September 10, 2025. https://ir.ionis.com/news-releases/news-release-details/ dawnzeratm-donidalorsen-approved-us-first-and-onlyrna-targeted

10. Riedl MA, et al. Patient-reported outcomes in the phase III OASIS-HAE study of donidalorsen for hereditary angioedema. Allergy. 2025;80(8):2361–2368. doi:10.1111/ all.16563

11. Phase 3 OASISplus data demonstrating benefit of donidalorsen for HAE patients who switched from other prophylactics published in JACI In Practice. Ionis. Published July 21, 2025. Accessed September 10, 2025. https://ir.ionis.com/news-releases/news-release-details/ phase-3-oasisplus-data-demonstrating-benefitdonidalorsen-hae

12. BioCryst announces FDA approval of ORLADEYO® (berotralstat) oral pellets, first and only oral prophylactic treatment for patients with HAE aged 2 to <12 years. BioCryst Pharmaceuticals, Inc. Published December 12, 2025. Accessed January 14, 2026. https://ir.biocryst. com/news-releases/news-release-details/biocrystannounces-fda-approval-orladeyor-berotralstat-oral

13. BioCryst announces positive results from APeX-P trial for ORLADEYO® (berotralstat) in pediatric patients with hereditary angioedema aged 2 to <12 years. BioCryst Pharmaceuticals, Inc. Published February 24, 2025. Accessed January 14, 2026. https://www.globenewswire. com/news-release/2025/02/24/3030956/0/en/ BioCryst-Announces-Positive-Results-from-APeX-PTrial-for-ORLADEYO-berotralstat-in-Pediatric-Patientswith-Hereditary-Angioedema-Aged-2-to-12-Years.html

14. Reality check: Hereditary angioedema. MMIT. Published 2019. Accessed September 23, 2025. https://info. mmitnetwork.com/hubfs/Reality%20Check%202019/ MMIT-Reality%20Check-HAE_1Q2019-final.pdf

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See us on the presentation stage, in breakout sessions or by visiting our booth in Music City Center.

Booth 1315 • AMCP Nashville

April 13–16 , 2026

Expo hours: Tuesday, 11 a .m . – 6 p.m . Wednesday, 9:30 a .m .–2:30 p.m .

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Natalie Sandoval, PharmD Director, Clinical Pharmacy

Myasthenia gravis

Treatment landscape and payer management

Myasthenia gravis (MG), a chronic neuromuscular autoimmune disease that causes weakness in the voluntary muscles (those that connect the bones, muscles in the face, throat and diaphragm) affects an estimated 75,000 to 100,000 people in the United States. The prevalence rate of MG is about 37 out of every 100,000 people in the United States.1,2

The three types of MG include autoimmune myasthenia, neonatal myasthenia and congenital myasthenia; neonatal and congenital myasthenia are rare.1 Two subtypes of autoimmune myasthenia are ocular MG, which weakens the muscles that move your eyes and eyelids, and generalized MG (gMG), which weakens eye muscles and those in the face, neck, arms, legs and throat.1

MG commonly presents with symptoms including weakness of the eyes, drooping of one or both eyelids, blurred or double vision, changes in facial expressions, difficulty swallowing, shortness of breath, impaired speech, and weakness in the arms, hands, fingers, legs and neck.1 These symptoms may not be immediately recognized as MG, as the degree of muscle weakness involved varies greatly among individuals with MG.1

The disease similarly affects both men and women across all racial and ethnic groups. While young adult women (under 40) and older men (over 60) are most impacted by MG, it can occur at any age, even childhood.1 Though MG is not inherited, it may occur in more than one member of the same family.

The disease is caused by interrupted nerve and muscle communication at the neuromuscular junction.1 Antibodies block, alter or destroy the receptors for acetylcholine at the neuromuscular junction, preventing the muscle from contracting.1 While MG is most often caused by antibodies to the acetylcholine receptor itself, antibodies to other proteins, such as the muscle-specific kinase (MuSK) protein, can impair transmission.1 The thymus gland may be associated with MG; in many adults with MG, the gland remains large even

after an individual becomes an adult. Additionally, those with MG typically have clusters of immune cells in the thymus gland and may develop thymomas, tumors in the thymus gland.1

Thymectomy may reduce symptoms and long-term medication needs in appropriate patients.

Diagnosis can be confirmed via several modalities.1 A physical and neurological examination is conducted to check muscle strength and tone, coordination, sense of touch and eye movements.1 Other diagnostic tests, including repetitive nerve stimulation and single-fiber electromyography, are also commonly used.1 In some cases, individuals with MG may have abnormally elevated levels of acetylcholine receptor antibodies or anti-MuSK

antibodies, which would be evident via blood test.1 MG can be difficult to diagnose, as muscle weakness is a common symptom of several other disorders.1

Treatment landscape

Treatment for MG focuses on improving neuromuscular transmission and reducing autoimmune activity using anticholinesterase agents and immunosuppressants.1 Thymectomy may reduce symptoms and long-term medication needs in appropriate patients.1 Short-acting therapies such as plasmapheresis and IVIG help manage acute exacerbations.1 Targeted options like complement inhibition provide additional treatment pathways alongside supportive lifestyle measures.1

Recent approvals

Nipocalimab-aahu (Imaavy)

In May 2025, the U.S. Food and Drug Administration (FDA) approved nipocalimab-aahu (Imaavy) for the treatment of gMG.3 This provides a new treatment alternative for the adult and pediatric population age 12 and older who are positive for anti-acetylcholine receptor (AChR)

Drug Manufacturer

zilucoplan sodium (Zilbrysq) Ra Pharmaceuticals; UCB

batoclimab (IMVT-1401) Immunovant; Roivant

gefurulimab (ALXN1720) AstraZeneca

efgartigimod alfa (Vyvgart) Argenx

telitacicept (RC18) RemeGen

cemdisiran (ALN-CC5) Alnylam Pharmaceuticals; Regeneron

pozelimab (Veopoz) Regeneron

cladribine (Mavenclad) EMD Serono

igtacopan (Fabhalta) Novartis

efgartigimod alfa; hyaluronidase (Vyvgart Hytrulo) Argenx; Halozyme

(Rystiggo)

remibrutinib (LOU064) Novartis

ravulizumab (Ultomiris IV) AstraZeneca

autoleucel (CABA-201) Cabaletta Bio

rapcabtagene autoleucel (YTB323) Novartis

Abbreviations: APRIL = A proliferation-inducing ligand; BAFF = B-cell activating

CAR T = chimeric antigen T-cell receptor therapy; CIC = citrate/isocitrate carrier; FcRn = fragment crystallizable receptor; IV = intravenous; SC = subcutaneous; siRNA = small interfering ribonucleic acid

In a 2025 U.S. claims analysis of patients with MG, the difference-indifference adjusted one-year total costs attributable to a new MG diagnosis were $25,799 for commercially insured patients and $4,927 for Medicare patients.

or anti- MuSK antibodies.3 Results from the pivotal Vivacity-MG3 trial informed the approval.3 The trial results demonstrated that nipocalimab with standard of care significantly improved disease control over 24 weeks against the placebo plus standard of care.4 Due to this improvement, subjects were able to regain essential daily functions such as swallowing, speaking, breathing and chewing.4 These improvements were maintained for up to 20 months of follow-up in the ongoing open-label extension study.5 Notably, nipocalimab demonstrated rapid and sustained reduction in autoantibody levels by up to 75% from the first dose and throughout a 24-week monitoring period.5

Nipocalimab demonstrated a consistent safety profile across the Vivacity-MG3 and ongoing Vibrance-MG trials, and a comparable tolerability was observed in both age groups.3-5

Inebilizumab-cdon (Uplizna)

In December 2025, the FDA approved inebilizumab-cdon (Uplizna) for the treatment of gMG in adults who are AChR and anti-MuSK antibody positive.6 This approval introduces an alternative targeted treatment option with

the potential for long-term disease control with just two doses a year after two initial loading doses.6 Data from the Myasthenia Gravis Inebilizumab Trial (MINT) supported the approval. MINT was the largest Phase 3 biologic study to include both AChR+ and MuSK+ patients and was the first to successfully incorporate a steroid taper into its protocol.7 Participants who were on steroids at baseline began tapering at Week 4 to reach 5 mg of prednisone per day by Week 24.7 Inebilizumab demonstrated a 1.9point difference in MG-ADL score when compared to the placebo at Week 26.7 In the AChR+ patient subgroup, benefits continued through Week 52, making this the longest randomized-controlled period for a Phase 3 trial in gMG.7 An exploratory analysis of AChR+ patients showed a 2.8 point difference in MG-ADL score for inebilizumab compared with the placebo.7 The most common adverse reactions were headache and infusion-related reactions.6

This approval marks the third indication for inebilizumab, which was previously approved by the FDA for anti–aquaporin-4 antibody positive neuromyelitis optica spectrum disorder in June 2020 and immunoglobulin G4-related disease in April 2025.6

Payer strategies

In a 2025 U.S. claims analysis of patients with MG, the difference-in-difference adjusted one-year total costs attributable to a new MG diagnosis were $25,799 for commercially insured patients and $4,927 for Medicare patients. An MG diagnosis leads to an increase in outpatient visits and inpatient admissions, emergency department visits and the length in hospital stay.8 Effective treatment and management have the potential to allow for more effective cost management and care. There remains an unmet need for clear, concise and well-defined guidelines for gMG treatment and management.9 Stronger evidence-based guidance is essential to support payer coverage decisions and care-management strategies.9

According to the 2025 Prime Therapeutics Medical Pharmacy Trend Report, health plans seem to be supporting shifts to lower-cost alternatives in place of Soliris.10 In the commercial line of business (LOB), Soliris utilizers declined nearly 30%, and Vyvgart utilizers rose by nearly 5% in 2024, with an annual cost per utilizer of $450,822 and $226,733, respectively.10 New spend for Vyvgart, Hytrulo and Rystiggo totaled $191,482 and $190,068 per utilizer, respectively.10 For the Medicare LOB, MG spend for Vyvgart decreased due to decreased

Stronger evidencebased guidance is essential to support payer coverage decisions and care-management strategies.

utilization, and there was a shift from Soliris to Ultomiris.10 In 2024, “Hematology: MG” was ranked at 14 in the top 20 commercial per member per month (PMPM) spend and 7 in the top 20 Medicare PMPM spend.10

As new treatment and targeted therapy alternatives are introduced for MG, there will be increased competition in the category. Management strategies will continue to be critical to mitigate costs, ensure appropriate access and address any gaps in care.

REFERENCES

1. Myasthenia gravis. National Institutes of Health. Accessed January 12, 2026. https://www. ninds.nih.gov/health-information/disorders/ myasthenia-gravis#toc-what-is-myasthenia-gravis-

2. Boxe, A. Myasthenia gravis prevalence. Myasthenia Gravis News. Published November 18, 2024. Accessed January 12, 2026. https://myastheniagravisnews.com/ myasthenia-gravis-prevalence/

3. FDA approves J&J’s Imaavy for generalised myasthenia gravis. Pharmaceutical Technology. Published May 1, 2025. Accessed September 9, 2025. https:// www.pharmaceutical-technology.com/news/ jj-imaavy-fda/?cf-view

4. Antozzi, C, Vu T, Sindhu R, et al. Safety and efficacy of nipocalimab in adults with generalised myasthenia gravis (Vivacity-MG3): a phase 3, randomised, double-blind, placebo-controlled study. Lancet Neuro. 2025;24(2):105–115. doi: 10.1016/S1474-4422(24)00498-8

5. Claeys, KG, Ait-Tihyaty M, Gandhi, K, et al. Efficacy of nipocalimab in open-label extension in patients transitioned from placebo: results from Vivacity-MG3 trial. Congress of the European Academy of Neurology. Published June 2025. Accessed January 12, 2026. https://www.jnjmedicalconnect.com/media/ attestation/congresses/neuroscience/2025/ean/ efficacy-of-nipocalimab-in-openlabel-extension-inpatients-transitioned-from-placebo-results-from.pdf

6. FDA approves Uplizna® for adults with generalized myasthenia gravis. Amgen. Published December 11, 2025. Accessed January 12, 2026. https://www.amgen.com/ newsroom/press-releases/2025/12/fda-approvesuplizna-for-adults-with-generalized-myasthenia-gravis

7. Nowak, RJ, Benatar M, Ciafaloni E, et al. A phase 3 trial of inebilizumab in generalized myasthenia gravis. New Eng J Med. 2025;392:2309–2320. doi: 10.1056/NEJMoa2501561

8. Choi, SA, Touchette DR, Kim K. Health care costs and resource utilization among patients with myasthenia gravis in the United States. J Manag Care Spec Pharm 2025;31(5):472–481. doi: 10.18553/jmcp.2025.31.5.472

9. Shaw, ML, Stein B, Kiran R. Advancing myasthenia gravis treatment access via guideline-directed expertise. American Journal of Managed Care. Published September 9, 2025. Accessed January 15, 2026. https://www.ajmc. com/view/advancing-myasthenia-gravis-treatmentaccess-via-guideline-directed-expertise

10. Medical Pharmacy Trend Report 2025 Fifteenth Edition. Prime Therapeutics. Published 2025. Accessed January 16, 2026. https://issuu.com/ primetherapeutics/docs/2025_medical_pharmacy_trend_ report?fr=sODQ4ZTgzNDUwNjE

Georgina Rubal-Peace, PharmD, BCPS

Director, Medication Use Policy

Banner Population Health Pharmacy Solutions

Spinal muscular atrophy

Key approvals, management strategies and pipeline activity

Spinal muscular atrophy (SMA) includes a group of rare hereditary diseases that affect motor neurons — specialized nerve cells in the brain and spinal cord that control movement in the arms, legs, face, chest, throat and tongue — as well as skeletal activity.1 The most common presentation of SMA is caused by changes in the survival motor neuron gene 1 (SMN1). There are five types of this form of SMA; each form is classified based on the average age of onset and severity of symptoms.1 Table 1 explores the traditional classifications of SMA caused by mutations in the SMN1 gene.1

SMN2, a gene very similar to SMN1, may be present in multiple copies; extra copies of the SMN2 gene are associated with the less severe forms of SMA (Types II-IV).1

SMA is an autosomal recessive disorder, meaning that the affected individual has two mutated genes, often inheriting one faulty gene from each parent.1 Inheriting only one mutated gene typically causes an individual to be a carrier of the disease without any symptoms.1 Individuals who have a family member with SMA or a family member who is a carrier may be at risk of being a carrier and can determine status via genetic carrier testing.1

Individuals with SMA have insufficient levels of the SMN protein responsible for maintaining the health and normal function of motor neurons.1 This deficiency can lead to loss of

Table 1. SMA classifications: Mutations in the SMN1 gene1

Type Description

• Very rare and severe

Symptoms begin prior to birth

Type 0

Type I (WerdnigHoffmann disease or infantile-onset SMA)

Type II

Type III (KugelbergWelander disease)

Type IV

• At birth, the infant has severe weakness and difficulty breathing and feeding

• Most common form

Usually evident prior to age 6 months

• Symptoms include severe muscle weakness and trouble breathing, coughing and swallowing

• Usually noticed between age 6 and 18 months

• Children with this type of SMA can sit without support but are unable to stand or walk without help

Symptoms show after age 18 months

• Children walk independently but may have difficulty doing so

• They may also have trouble running, rising from a chair or climbing stairs

• Develops after age 18

Symptoms include mild to moderate leg muscle weakness and other symptoms

motor neurons in the spinal cord, causing weakness and wasting of the skeletal muscles, which can, in turn, lead to difficultly moving, breathing and swallowing. While symptoms can range in severity, the course of the disease is progressive and irreversible.1

Diagnosis

SMA is diagnosed through a genetic blood test that detects mutations or deletions in the SMN1 gene, which identifies at least 95% of SMA Types I, II and III.1 In the event that the SMN1 gene tests normal, or an individual’s history and exam are not typical of SMA, other diagnostic tests can be run, including electromyography, nerve conduction velocity studies and muscle biopsy.1 In addition, newborn screening for SMA is now offered in all 50 states, which allows for earlier detection and intervention for infants born with SMA.

Treatment landscape

Currently approved and available treatments for SMA include nusinersen (Spinraza), onasemnogene abeparvovec-xioi (Zolgensma) and risdiplam (Evrysdi).1 Nusinersen is an antisense oligonucleotide approved for

pediatric and adult patients. It is administered intrathecally, starting with four loading doses over two months, then every four months thereafter.1 Onasemnogene abeparvovec–xioi is an adeno-associated viral (AAV) vector gene therapy for children younger than 2 years old, which is given as a one-time intravenous infusion.1 Risdiplam is a small molecule for pediatric and adult patients that is available as a liquid formulation for oral or feeding tube administration.1 These therapies preserve motor neurons, improve muscle function and extend lives, but they are not cures. Because SMA is a progressive and irreversible disease with rapid functional decline early in the disease course, treatment should be initiated as soon as possible after diagnosis. The chosen treatment should consider factors such as route and frequency of administration, possible side effects and monitoring requirements.1

In addition to initiating pharmacotherapy, individuals with SMA can benefit from other treatments, including physical therapy, occupational therapy, and rehabilitation to improve posture, joint immobility, and muscle weakness and atrophy.1 Additional therapy is sometimes required for those with speech and swallowing difficulties. Assistance devices may be helpful for improving functional independence.1

Recent and upcoming approvals

Onasemnogene abeparvovec-brve (Itvisma)

In November 2025, the U.S. Food and Drug Administration (FDA) approved onasemnogene abeparvovec-brve (Itvisma) for the treatment of SMA in adult and pediatric patients age 2 and older with confirmed mutation in the SMN1 gene.2 This is an AAV vector-based gene therapy that contains the same active ingredient as Zolgensma. Approval was based on results of Phase 3 studies, which demonstrated improvement in the Hammersmith Functional Motor Scale Expanded (HFMSE) score.2 The study met its primary endpoint of change from baseline to 52 weeks in HFMSE score, with onasemnogene abeparvovec demonstrating a statistically significant 2.39-point improvement on the HFMSE versus 0.51 points in the placebo group, in treatment-naïve patients.3 An open-label Phase 3b study in patients who discontinued treatment with nusinersen or risdiplam also showed improvement in the HFMSE score.3

Novartis provided adequate data to expand the indication to include all adult patients with SMA; however, warnings and precautions are warranted due to the potentially increased risks of adverse events of special interest in adult patients with preexisting chronic medical conditions.2 These adverse events include hepatotoxicity and cardiotoxicity.2

While the active ingredient in Itvisma is identical to Zolgensma, it is a more concentrated formula, which allows for larger doses in a small volume to be administered.2 Itvisma is administered directly to the central nervous system via a single intrathecal injection.2

Nusinersen (Spinraza HD)

An FDA approval decision on high-dose nusinersen (Spinraza HD, Biogen) is anticipated in April. This new regimen consists of a more rapid loading-dose phase followed by a higher maintenance dose, also given every four months. The review application was accepted based on data from the DEVOTE Phase 2/3 randomized, controlled, dose-escalating study, which was designed to evaluate safety, tolerability, pharmacokinetics and efficacy of nusinersen when administered at a higher dose (50/28 mg). The DEVOTE study enrolled 145 participants across ages and SMA types and included an open-label safety evaluation cohort (Part A); a double-blind, active randomized treatment cohort (Part B); and an open-label

In addition to initiating pharmacotherapy, individuals with SMA can benefit from other treatments, including physical therapy, occupational therapy, and rehabilitation.

treatment cohort (Part C) to assess safety and tolerability of transitioning participants from the currently approved dose of SPINRAZA 12 mg to the higher-dose regimen being tested in the study.4 The pivotal cohort (Part B) involved treatment-naïve children with infantile-onset SMA, who were randomized 2:1 to receive the higher dose regimen on the currently approved lower-dose regimen.5 The study achieved a statistically significant improvement in motor function (as measured by change from baseline on the Children’s Hospital of Philadelphia-Infant Test

of Neuromuscular Disorders [CHOP INTEND]) in infants who received the higher-dose regimen as compared to a prespecified, matched control group, meeting its primary endpoint.5 In addition, the safety profile and incidence of adverse events was similar to that of the lower-dose regimen.5

In September 2025, the FDA issued a Complete Response Letter (CRL) for Spinraza HD due to Chemistry Manufacturing and Controls (CMC) issues.6 While this was unexpected, the FDA did not identify any concerns with the clinical data for Biogen’s high-dose regimen.6 The application was resubmitted in November 2025 and an FDA decision is anticipated for April 2026.

Management strategies

In 2025, the Institute for Clinical and Economic Review (ICER) published Therapies for Spinal Muscular Atrophy: Effectiveness and Value.7 The ICER review recognizes the substantial impact of disease-modifying therapies on improvement in SMA care, citing a 77% reduction in mortality, which is likely due to the available treatments as well as the adoption of newborn screening. There are no head-to-head trials comparing the effectiveness of nusinersen, onasemnogene abeparvovec and risdiplam. However, the ICER concludes that all three agents have strong evidence of treatment benefits, such as increased survival, avoidance of permanent ventilation and major motor milestones achievement.7

Payer insights

In a 2020 Academy of Managed Care and Specialty Pharmacy (AMCP) market insights program, payers discussed how they identified and managed patients with SMA and established coverage criteria for new SMA therapies.8 Overall, the payer participants noted that the population was managed through multidisciplinary supportive care; acknowledged the substantial effect SMA has on the quality of life of patients, caregivers and family; and are mindful that, during decision-making, delays in treatment increase the risk for greater damage to motor neurons.8 The majority of payers — all but one — had developed coverage criteria for gene therapy in this category, which will be critical as additional gene therapies are approved and enter the market.8

Gaps in care

As gene therapies have extended survival in patients with SMA, improved care transitions from pediatric to adult systems are required.9 There are gaps in knowledge around care strategies for adult patients with the disease, and the transition can present challenges.9 Patients with

As gene therapies have extended survival in patients with SMA, improved care transitions from pediatric to adult systems are required.

SMA are now living into their 20s; however, the available system lacks appropriate staffing and specialists to address the complex needs and support required of older patients.9 Optimized, multidisciplinary care, with an approach that spans both pediatric and adult populations, is critical to effective management for this population. Optimizing this system will require a combination of knowledge, training and education, all key to streamlining the care transition process.

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REFERENCES

1. Spinal muscular atrophy. National Institute of Neurological Disorders and Stroke. Accessed January 13, 2026. https:// www.ninds.nih.gov/health-information/disorders/ spinal-muscular-atrophy

2. Office of the Commissioner. FDA approves gene therapy for treatment of spinal muscular atrophy. U.S. Food and Drug Administration. Published November 24, 2025. Accessed January 13, 2026. https://www.fda.gov/ news-events/press-announcements/fda-approvesgene-therapy-treatment-spinal-muscular-atrophy

3. New Novartis phase III data demonstrate meaningful efficacy and safety results of intrathecal onasemnogene abeparvovec in broad patient population with SMA. GlobeNewswire. Published March 19, 2025. Accessed January 13, 2026. https://www.globenewswire.com/ news-release/2025/03/19/3045454/0/en/New-NovartisPhase-III-data-demonstrate-meaningful-efficacyand-safety-results-of-intrathecal-onasemnogeneabeparvovec-in-broad-patient-population-with-SMA.html

4. FDA and EMA accept applications for higher dose regimen of nusinersen in SMA. Biogen. Published January 23, 2025. Accessed January 13, 2026. https://investors. biogen.com/news-releases/news-release-details/ fda-and-ema-accept-applications-higher-dose-regimennusinersen

5. Biogen announces positive topline results from study of higher dose regimen of nusinersen, showing significant benefit in treatment of SMA. GlobeNewswire. Published September 4, 2024. Accessed January 13, 2026. https://www.globenewswire. com/news-release/2024/09/04/2940411/0/en/ Biogen-Announces-Positive-Topline-Results-fromStudy-of-Higher-Dose-Regimen-of-NusinersenShowing-Significant-Benefit-in-Treatment-of-SMA.html

6. Biogen receives news on supplemental new drug application (sNDA) for high dose nusinersen from the U.S. FDA. Cure SMA. Published September 23, 2025. Accessed January 20, 2026. https://www.curesma.org/biogenreceives-news-on-supplemental-new-drug-applicationsnda-for-high-dose-nusinersen-from-the-u-s-fda/

7. Therapies for spinal muscular atrophy: Final policy recommendations. Institute for Clinical and Economic Review. Published September 2, 2025. Accessed January 14, 2026. https://icer.org/wp-content/uploads/2025/09/ ICER-SMA-Policy-Recommendations_ForPublication_090225.pdf

8. Brixner, DI. Payer perspectives on the treatment landscape of spinal muscular atrophy — Findings from the AMCP Market Insights Program. AMCP. Published June 17, 2020. Accessed January 29, 2026. https://www.amcp.org/ sites/default/files/2020-06/AMCP_SMAMarketInsights_ Webinarslides_06172020.pdf

9. Mattina, C. Solving the transition conundrum as more children with muscular dystrophy live to adulthood. AJMC. Published March 17, 2025. Accessed January 14, 2026. https://www.ajmc.com/view/ solving-the-transition-conundrum-as-more-childrenwith-muscular-dystrophy-live-to-adulthood

Pipeline

nusinersen (Spinraza) high dose Biogen SMA (high-dose)

tividenofusp alfa Denali Therapeutics

allogeneic T-cell immunotherapy (Orca-T) Orca Bio

II (Hunter syndrome)

malignancies

nivolumab (Opdivo) Bristol Myers Squibb Classical Hodgkin lymphoma

vusolimogene oderparepvec (RP1) Replimune Melanoma

sparsentan (Filspari) Travere Therapeutics, Bristol Myers Squibb Focal segmental glomerulosclerosis

doravirine/islatravir Merck HIV-1 infection (adults)

(Sarclisa) SC

teplizumab-mzwv (Tzield) Sanofi

dextromethorphan/ bupropion (Auvelity) Axsome Therapeutics

(delay progression from stage 2 to 3, age 1–7)

dupilumab (Dupixent) Sanofi Urticaria (age 2–11)

(Stelara) Janssen

Pipeline drug list (cont.)

efgartigimod alfa (Vyvgart) Argenx MG (AchR)

golimumab (biosimilar to Janssen’s Simponi) Bio-Thera Solutions RA; PsA; UC

fam-trastuzumab deruxtecan-nxki (Enhertu) Daiichi Sankyo, AstraZeneca

Breast cancer (neoadjuvant, HER2+, stage 2-3)

acalabrutinib (Calquence) AstraZeneca CLL (treatment-naïve, in combination with venetoclax)

human insulin (Afrezza) MannKind T1DM (age 4–17); T2DM (age 4–17) Inhaled sBLA 05/29/2026

dexmethylphenidate IR/ ER formulation Cingulate

brimonidine tartrate 0.35% (once-daily) Ocuvex Therapeutics Glaucoma/ocular hypertension

guselkumab (Tremfya) Janssen PsA (structural damage inhibition)

lecanemab-irmb (Leqembi Iqlik) autoinjector Eisai, Biogen Alzheimer’s disease (SC starting dose)

lumateperone (Caplyta) Intra-Cellular Therapies Schizophrenia (relapse prevention)

venetoclax (Venclexta) Abbvie CLL

vepdegestrant Arvinas, Pfizer

Breast cancer (advanced or metastatic, HR+, HER2-, ESR1mutated, prior ERT)

ensitrelvir Shionogi COVID-19 post-exposure prophylaxis

nilotinib Xspray Pharma CML

cytisinicline Achieve Life Sciences

(nicotine dependence)

sirolimus/pegadricase Sobi Gout

roflumilast 0.3% cream (Zoryve) Arcutis Biotherapeutics

(age 2–5)

veligrotug Viridian Therapeutics Thyroid eye disease

pegargiminase Polaris Group Mesothelioma (malignant pleural, non-epithelioid histology)

bulevirtide 10 mg Gilead Sciences Chronic HDV

camizestrant AstraZeneca

cancer (advanced, HR+, HER2-, ESR1-mutated)

immune globulin, humansira (Asceniv) ADMA Biologics Primary immunodeficiencies (age > 2)

oxylanthanum carbonate (Renazorb) Unicycive Therapeutics Hyperphosphatemia (in patients with CKD on dialysis)

Pipeline drug list (cont.)

respiratory syncytial virus vaccine, adjuvanted (Arexvy) GSK RSV immunization (age 18–49 at increased risk)

tebipenem HBr GSK, Spero Therapeutics UTI (complicated)

DB-OTO Regeneron

anifrolumab-fnia (Saphnelo) SC

baxdrostat

capivasertib (Truqap) AstraZeneca

durvalumab (Imfinzi)

marstacimab-hncq (Hympavzi)

pivekimab sunirine

Abbvie, Jazz Pharmaceuticals

sacituzumab govitecanhziy (Trodelvy) Gilead Sciences

sasanlimab Pfizer

sonrotoclax BeOne Medicines

zidebactam/cefepime (Zaynich) Wockhardt

atacicept Vera Therapeutics, Bristol Myers Squibb

Congenital hearing loss (otoferlin gene variants)

Systemic lupus erythematosus

Hypertension (resistant or uncontrolled)

Prostate cancer (PTEN-deficient, metastatic, hormone-sensitive)

cancer (high-risk, nonmuscle invasive)

A or B (with inhibitors)

Blastic plasmacytoid dendritic cell neoplasm

cancer (metastatic TNBC, first-line)

Bladder cancer (high-risk, nonmuscle-invasive, in combination with BCG)

Mantle cell lymphoma (R/R, prior BTK inhibitor)

A nephropathy (Berger’s disease)

relacorilant Corcept Therapeutics Ovarian cancer (platinum-resistant)

gedatolisib Celcuity, Pfizer

cancer (HR+, HER2-, PIK3CA wild-type)

furosemide (Furoscix) ReadyFlow autoinjector MannKind Edema (adults with CKD or chronic HF)

icotrokinra Janssen, Protagonist Therapeutics Plaque psoriasis (age > 12)

anitocabtagene autoleucel

Gilead Sciences

apixaban oral dissolving film (TAH3311) Taho Pharmaceuticals

beclomethasone/ formoterol/glycopyrrolate Chiesi Farmaceutici

drug list (cont.)

denecimig Novo Nordisk

alfa

pariglasgene brecaparvovec (DTX401) Ultragenyx Pharmaceutical Glycogen storage disease (type 1a)

adrabetadex Mandos Health Niemann-Pick disease type C

bezuclastinib Cogent Biosciences

(nonadvanced, systemic)

imlifidase Sarepta Therapeutics Kidney transplant rejection

imsidolimab Vanda Pharmaceuticals Generalized pustular psoriasis

molgramostim Savara Acute pulmonary alveolar proteinosis

rusfertide Takeda Pharmaceuticals Polycythemia vera

ustekinumab (Stelara) Janssen UC (ags 2–17)

Abbreviations: AA = Accelerated Approval; AchR = acetylcholine receptor; ADHD = attention deficit hyperactivity disorder; BCG = Bacillus Calmette-Guerin; BLA = Biologics License Application; BT = Breakthrough Therapy; BTK = Bruton’s tyrosine kinase; CD = Crohn’s disease; CKD = chronic kidney disease; CLL = chronic lymphocytic leukemia; CML = chronic myelogenous leukemia; CNPV = Commissioner’s National Priority Voucher; ESR-1 = estrogen receptor 1; FT = Fast Track; HDV = hepatitis D virus; HER2 = human epidermal growth factor receptor 2-negative; HF = heart failure; HR = hormone receptor; IM = intramuscular; IV = intravenous; MG = myasthenia gravis; MM = multiple myeloma; NDA = New Drug Application; OD = orphan drug; PIK3CA = phosphatidylinositol-3-kinase catalytic subunit alpha; PR = Priority Review; PsA = psoriatic arthritis; PTEN = phosphatase and tensin homolog; QIDP = Qualified Infectious Disease Product; RA = rheumatoid arthritis; R/R = relapsed/refractory; RMAT = Regenerative Medicine Advanced Therapy; RPD = rare pediatric disease; RSV = respiratory syncytial virus; RTOR = Real-Time Oncology Review; sBLA = supplemental Biologics License Application; SC = subcutaneous; SMA = spinal muscular atrophy; sNDA = supplemental New Drug Application; T1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus; TNBC = triple-negative breast cancer; UC = ulcerative colitis; UTI = urinary tract infection