Cell and Gene Therapies

The FDA last month approved two new gene therapies for Duchenne Muscular Dystrophy (DMD) and hemophilia A, and major PBMs tell AIS Health, a division of MMIT, that they have not yet decided how to cover the new treatments. If current trends are any indication, health plans will impose strict utilization management requirements and attempt to negotiate outcomes-based reimbursement pacts with the treatments’ manufacturers.

The FDA on June 22 granted accelerated approval to Sarepta Therapeutics, Inc.’s Elevidys (delandistrogene moxeparvovec-rokl), the DMD treatment. It will have a list price of $3.2 million. BioMarin Pharmaceutical Inc.’s Roctavian (valoctocogene roxaparvovec), for hemophilia A, gained full FDA approval on June 29, and will have a list price of $2.9 million. Both therapies are administered as a one-time dose. Roctavian also typically requires an indefinite period of simultaneous treatment with corticosteroids to reduce patients’ immune-system response to the gene therapy.

June 14: The FDA expanded the label of Pfizer Inc.’s Abrilada (adalimumab-afzb) to include the treatment of moderate to severe hidradenitis suppurativa in adults. The agency first approved the biosimilar of AbbVie Inc.’s Humira (adalimumab) on Nov. 15, 2019. Dosing starts with 160 mg via subcutaneous injection on day one or split over two consecutive days, then 80 mg on day 15, and then on day 29 and subsequent doses, 40 mg every week or 80 mg every other week. Drugs.com lists the price of two 40 mg/0.4 mL kits and two 40 mg/0.8 mL kits of Humira, each with two devices, as more than $7,299. Pfizer told AIS Health, a division of MMIT, that it would launch the tumor necrosis factor (TNF) inhibitor in “late third-quarter/early fourth-quarter 2023” per the settlement of patent litigation with AbbVie.

Specialty drug management continues to be of utmost importance to plan sponsors, which are implementing a variety of levers to try to keep spending in check while making sure their beneficiaries are receiving appropriate care. Pharmaceutical Strategies Group (PSG), an EPIC company, recently released its 2023 Trends in Specialty Drug Benefits Report, which examines the use of these strategies and overall trends in managing these costly medications.

The report, released May 3, is the 10th annual report; it previously was published under the Pharmacy Benefit Management Institute (PBMI) brand. Conducted from Sept. 20, 2022, through Oct. 21, 2022, the survey included 182 benefits leaders from employers, unions/Taft-Hartley plans and health plans representing plan sponsors of approximately 86.7 million covered lives. Genentech USA, Inc., a member of the Roche Group, co-sponsored the report with PSG.

While the cell and gene therapy (CGT) industry has shown remarkable progress, it still has some barriers to overcome. The FDA is taking numerous steps to help bring these products onto the market, asserted Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research (CBER), the unit that oversees biological products, including vaccines, allergenic products, blood and blood products, and cellular, tissue, and gene therapies, at a recent public appearance.

“I think the bottom line here for us is that we are very committed to helping move this field forward for populations of all sizes,” particularly for small populations, which is “one of the areas that is our highest medical need right now,” said Marks during a session in the CGT track at the Reuters Pharma USA conference, held March 28 and 29 in Philadelphia.

Sessions during the cell and gene therapy (CGT) track at the Reuters Pharma USA conference, held March 28 and 29 in Philadelphia, echoed much of the same advice for pharma companies commercializing one of these products. Starting the process early and collaborating with and forming partnerships with a variety of stakeholders are critical steps to success, multiple speakers emphasized.

Companies looking to bring a cell and gene therapy (CGT) to market should start preparing early on issues such as manufacturing and logistical matters, market access and patient access, advised Warner Biddle, senior vice president and global head of commercial for Kite Pharma, a Gilead Sciences, Inc. company. Kite has two chimeric antigen receptor T-cell therapies on the U.S. market: Yescarta (axicabtagene ciloleucel) — the second CAR-T to secure FDA approval — and Tecartus (brexucabtagene autoleucel).

In late 2022, the FDA approved the first gene therapy for bladder cancer, Ferring Pharmaceuticals’ Adstiladrin (nadofaragene firadenovec-vncg). Almost three-quarters of oncologists surveyed by Zitter Insights expressed at least moderate interest in the agent, and payers said they expect to manage the drug to label. While the drug gives another treatment alternative to a much-needed area, it likely will continue to put financial pressure on payers, industry experts tell AIS Health, a division of MMIT.

On Dec. 16, the FDA approved Adstiladrin for the treatment of adults with high-risk, Bacillus Calmette-Guerin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors. The agency gave the novel adenovirus vector-based gene therapy priority review, breakthrough therapy and fast track designations. Dosing is once every three months into the bladder via a urinary catheter. The company said it expects the therapy to be available in the second half of 2023.

While drugs are increasingly hitting the market that address unmet needs and even offer cures for some rare diseases, private insurers are highly concerned about such therapies’ eye-popping price tags, a recent survey indicated. But one prominent payer executive who spoke during AHIP’s Medicare, Medicaid, Duals & Commercial Markets Forum suggested that insurers are better off working collaboratively with drugmakers to ensure prices are tied to value — rather than engaging in an inter-industry war of words.

“More and more we’re seeing drugs come through with limited evidence through accelerated approval processes, which generally is a marker for an unmet need, which is a good thing. But the evidence can be thin,” said Michael Sherman, M.D., executive vice president and chief medical officer of Point32Health. During a March 14 panel at the AHIP forum, Sherman pointed to the example of Makena (hydroxyprogesterone caproate), a drug that aims to reduce preterm births but failed to prove clinical effectiveness in trials conducted after it received accelerated approval. With the FDA poised to make a final decision on the drug’s status, Clovis Pharma Group recently announced it would voluntarily pull Makena off the market.

The FDA recently approved the first gene therapy for bladder cancer, Ferring Pharmaceuticals’ Adstiladrin (nadofaragene firadenovec-vncg). Almost three-quarters of oncologists surveyed by Zitter Insights expressed at least moderate interest in the agent, and payers said they likely will manage the drug to label.

On Dec. 16, the FDA approved Adstiladrin for the treatment of adults with high-risk, Bacillus Calmette-Guerin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors. The agency gave the novel adenovirus vector-based gene therapy priority review, breakthrough therapy and fast track designations. Dosing is once every three months into the bladder via a urinary catheter. The company said it expects the therapy to be available in the second half of 2023.

The FDA recently approved the fifth and sixth gene therapies, with four of those decisions coming in the second half of 2022. While payer respondents to a Zitter Insights survey have expressed interest in hemophilia B treatment Hemgenix (etranacogene dezaparvovec-drlb), its price may prove to be an obstacle to coverage.

On Nov. 22, the FDA approved uniQure N.V.’s Hemgenix for the treatment of people at least 18 years old with hemophilia B who currently use factor IX prophylaxis therapy or have current or historical life-threatening hemorrhage or have repeated serious spontaneous bleeding episodes. CSL Behring LLC, a CSL business, will market the gene therapy. The agency gave the first-in-class adeno-associated virus A5-based gene therapy — which previously was known as EtranaDez — priority review and orphan and breakthrough therapy designations.

Jan. 19: The FDA expanded the label of BeiGene, Ltd.’s Brukinsa (zanubrutinib) to include the treatment of adults with chronic lymphocytic leukemia or small lymphocytic lymphoma. The agency initially approved the Bruton’s tyrosine kinase (BTK) inhibitor on Nov. 14, 2019. The agency granted the application orphan drug designation, and its review used the Assessment Aid. The recommended dose of the capsule is 160 mg twice daily or 320 mg once daily. Drugs.com lists the price of 120 80 mg capsules as more than $15,264.

Jan. 19: The FDA granted accelerated approval to Seagen Inc.’s Tukysa (tucatinib) in combination with trastuzumab for the treatment of adults with RAS wild-type, human epidermal growth factor receptor 2 (HER2)-positive unresectable or metastatic colorectal cancer that has progressed following treatment with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy. The company says the tyrosine kinase inhibitor is the first FDA-approved treatment in HER2-positive metastatic colorectal cancer. The agency first approved the drug on April 17, 2020. The newest indication had priority review and breakthrough therapy designation. Dosing for the tablet is 300 mg twice daily. Drugs.com lists the price of 60 150 mg tablets as more than $12,389.