Drug Approvals

This past year, the FDA continued to rebound from a drop in approvals, marking the highest number in years. The agency’s Center for Drug Evaluation and Research (CDER) approved 55 novel drugs last year, and its Center for Biologics Evaluation and Research (CBER) approved 17 agents. That’s up from 37 CDER-approved therapies in 2022 and 51 in 2011. In 2022, CBER OK’d 13 agents, up from 10 in 2021. Specialty agents, such as cell and gene therapies, continued to make up a large portion of those new approvals, while the FDA approved several biosimilars, including a handful that were the first versions of their reference drugs. AIS Health, a division of MMIT, spoke with industry experts about what they view as the most notable FDA approvals of 2023.

In December, the FDA approved the two newest cell and gene therapies, which were the first such agents approved for the treatment of sickle cell disease. As more of these products launch onto the U.S. market — the agency previously predicted that it would be approving 10 to 20 of the treatments by 2025 — payers are taking a variety of approaches to managing the therapies. Cost remains the main obstacle to their use, but their long-term durability also remains a question to some extent.

Dec. 8 saw the newest approvals, both for the treatment of sickle cell disease in people at least 12 years old: bluebird bio, Inc’s Lyfgenia (lovotibeglogene autotemcel; lovo-cel) and Vertex Pharmaceuticals Inc. and CRISPR Therapeutics’ Casgevy (exagamglogene autotemcel; exa-cel). The latter agent is the first CRISPR/Cas9 genome-edited cell therapy that the FDA has approved. The FDA gave both applications priority review, orphan drug, fast track and regenerative medicine advanced therapy designations. It also gave Lyfgenia rare pediatric disease designation.

The approval of Eli Lilly and Co.’s Zepbound (tirzepatide) in November capped off a banner year for glucagon-like peptide 1 (GLP-1) agonists and their use in weight loss management. And the fuss over these much-hyped obesity drugs — originally approved to treat diabetes — is likely just beginning. While employer groups and commercial payers are agonizing over the potential cost of coverage, industry leaders and legislators are pushing for Medicare to cover GLP-1s as weight loss therapies. Medicaid programs, meanwhile, are also weighing their options.

GLP-1s are now “the No. 1 driver of non-specialty pharmacy trend,” Mercer’s lead pharmacy actuary Jon Lewis told AIS’s Health Plan Weekly in November. Zepbound joins fellow GLP-1s from Novo Nordisk A/S, Wegovy (semaglutide) and Saxenda (liraglutide), in the obesity market basket. (As diabetes therapies, Zepbound is marketed as Mounjaro, while Wegovy is known as Ozempic.) Despite crackdowns on off-label use of the drugs’ diabetes iterations and a seemingly endless wave of shortages, many in the industry are clamoring for increased consumer access to the drugs. The American Medical Association on Nov. 13 passed a resolution asking “health insurers to provide coverage of available FDA-approved weight-loss medications, including GLP-1 medications, to demonstrate a commitment to the health and well-being of our patients.”

The FDA recently approved the two newest cell and gene therapies, with one of them earning the distinction of being the first of its kind approved by the FDA. As more of these products launch onto the U.S. market — the agency previously predicted that it would be approving 10 to 20 of the treatments by 2025 — payers are taking a variety of approaches to managing the therapies.

Dec. 8 saw the newest approvals, both for the treatment of sickle cell disease in people at least 12 years old: bluebird bio, Inc’s Lyfgenia (lovotibeglogene autotemcel; lovo-cel) and Vertex Pharmaceuticals Inc. and CRISPR Therapeutics’ Casgevy (exagamglogene autotemcel; exa-cel). The latter agent is the first CRISPR/Cas9 genome-edited cell therapy that the FDA has approved. The one-time treatments come with hefty price tags: Lyfgenia is priced at $3.1 million and Casgevy at $2.2 million.

The ulcerative colitis (UC) space has seen multiple new approvals recently that could focus payer management even more on the condition. Payers already take an aggressive approach toward managing branded agents within the class, according to a Zitter Insights survey. That stance, say industry experts, will only grow with the new drugs and administration routes.

While no cure exists for the inflammatory bowel disease, the FDA has approved numerous agents to treat signs and symptoms of the condition. In addition to the nine biosimilars of AbbVie Inc.’s Humira (adalimumab) that have launched in the U.S. in 2023, a handful of other approvals happened from late September through late October. All of the agents offer maintenance dosing either through an oral or subcutaneous route of administration.

Oct. 30: The FDA gave an additional approval to Bristol Myers Squibb’s Orencia (abatacept) for the subcutaneous treatment of people at least 2 years old with active psoriatic arthritis. The agency first approved the selective T cell costimulation modulator on Dec. 23, 2005. Dosing for the newest use is 50 mg once weekly for people with a body weight of 10 kg to less than 25 kg, 87.5 mg for those with a body weight of 25 kg to less than 50 kg and 125 mg for those with a body weight of at least 50 kg. The agent also is approved for intravenous dosing of certain indications. GoodRx lists one carton of four 125 mg/mL single-dose syringes as more than $5,520.

Oct. 31: The FDA expanded the approval of Fresenius Kabi’s Idacio (adalimumab-aacf) for the treatment of adults with non-infectious intermediate and posterior uveitis and panuveitis. The agency first approved the biosimilar of AbbVie Inc.’s tumor necrosis factor (TNF) blocker Humira (adalimumab) on Dec. 13, 2022. Dosing starts with 80 mg via subcutaneous injection, followed by 40 mg every other week starting one week after the initial dose. The price of two single-dose prefilled pens or two single-dose prefilled glass syringes is $6,576.

The US Food and Drug Administration’s simultaneous approval of two gene therapies for sickle cell disease from Vertex Pharmaceuticals Incorporated/CRISPR Therapeutics AG and bluebird bio on 8 December provides the competitors an equal start out of the gate, and offers another test for the Rx policy concept that intra-class competition can drive down prices.

Based on the initial list prices, though, it seems like perhaps competition cannot do that, at least not in this case, or at least not yet. Bluebird bio’s Lyfgenia has a wholesale acquisition cost of $3.1m, while the WAC for Vertex and CRISPR’s Casgevy is $2.2m, which might be a significant handicap for bluebird in securing reimbursement.

Bayer recently revealed that it will work with the FDA to voluntarily withdraw the New Drug Application (NDA) for its cancer drug Aliqopa (copanlisib). The therapy is the latest phosphoinositide 3-kinase — also called phosphatidylinositol 3-kinase — (PI3K) inhibitor/indication with accelerated approval to treat a hematologic malignancy to be pulled from the U.S. market, potentially spurring payers to take a closer look at these agents.

The agency gave Aliqopa accelerated approval on Sept. 14, 2017, for the treatment of adults with relapsed follicular lymphoma (FL) who have received at least two systemic therapies. Approval was based on the CHRONOS-1 Phase II clinical trial. In the confirmatory study, CHRONOS-4, adding Aliqopa to standard immunochemotherapy regimens did not meet the primary endpoint of progression-free survival (PFS) vs. the standard immunochemotherapy control arm. Bayer says it will publish the trial results “in a timely manner.”

The recent approvals of the first two gene therapies for sickle cell disease represent potential major breakthroughs for patients who have faced significant burdens associated with the condition. However, there are still questions about how and whether payers will cover the high-cost treatments and how many patients will be open to taking the new treatments.

The FDA on Dec. 8 approved Casgevy (exagamglogene autotemcel) from CRISPR Therapeutics and Vertex Pharmaceuticals Inc. and Lyfgenia (lovotibeglogene autotemcel) from bluebird, Inc. for patients who are 12 or older and have recurrent vaso-occlusive events (VOEs), the term for severe pain and organ damage. The agency noted about 100,000 people in the U.S. have sickle cell disease and that VOEs “can lead to life-threatening disabilities and/or early death.”

Scrutiny of the FDA’s accelerated approval process has shown no signs of slowing, with an FDA committee holding a recent meeting on the program’s use for oncology indications, as well as on two cancer drugs lacking confirmatory trial data long after their accelerated approvals. And an FDA leader recently asserted his stance on granting the designation only when companies already have started postmarketing trials. Still, these developments should not dampen interest by either manufacturers or payers in drugs hitting the market via the accelerated pathway, says one industry expert.

The FDA established the accelerated approval pathway in 1992 to bring HIV/AIDS medicines onto the market sooner during the ongoing epidemic. Between that time and Dec. 31, 2020, the agency has granted more than 253 accelerated approvals, according to a 2021 report from the Institute for Clinical and Economic Review (ICER) examining the designation. Of those, 125 — 49.4% — later received full approval, with a median time of 3.2 years from accelerated approval to full. Sixteen — 6.3% — of the indications have been withdrawn, and the remaining 112 drugs have been on the market for a median of 1.9 years.