The FDA ramped up approvals and reconsidered some notable existing drugs
2023 was marked by several first-time approvals, while some previously approved drugs came under scrutiny
If 2022 was a sparse year for US Food and Drug Administration approvals of new molecular entities, 2023 was a return to the pace the agency had achieved from 2017 through 2021. By mid-September, the FDA had already surpassed the 37 approvals it had made in all of 2022 and by mid-November reached 50 approvals.
In addition to approving firsts in prescription drugs and vaccines, the agency approved over-the-counter versions of a birth control pill and naloxone, used for reversing opioid overdoses, for the first time. Also making headlines this year, FDA advisory panels scrutinized an ingredient in popular over-the-counter cold medicines and a trial of a first-in-class cancer drug.
Leqembi was approved to treat Alzheimer’s disease
Eisai and Biogen’s Leqembi (lecanemab) became the second monoclonal antibody drug to receive accelerated FDA approval to treat Alzheimer’s disease on Jan. 6. It then received full approval from the agency—a first for this class of Alzheimer’s treatment—on July 6. In 2021, the FDA granted accelerated approval to Biogen and Eisai’s monoclonal antibody Aduhelm (aducanumab), but the decision was controversial; many doctors and scientists argued that clinical trials of Aduhelm showed no benefit to patients. Both drugs clear amyloid-β deposits in the brains of people with Alzheimer’s disease. But unlike Aduhelm, Leqembi slowed cognitive decline, albeit modestly, in clinical trials of people with early-stage Alzheimer’s. The FDA is expected to decide on approval for another monoclonal antibody treatment for Alzheimer’s, Eli Lilly and Company’s donanemab, by the end of the year.
Zurzuvae got the nod for the treatment of postpartum depression but not major depressive disorder
The FDA granted approval to Sage Therapeutics and Biogen’s Zurzuvae (zuranolone) as the first oral treatment for postpartum depression on Aug. 4. Previously approved treatments for postpartum depression have to be injected. Zurzuvae is a neuroactive steroid that modulates γ-aminobutyric acid (GABA) receptors in the central nervous system, thereby calming nerve activity. But the FDA rejected the drug as a treatment for major depressive disorder. That split decision was bad news for both firms, which saw their share prices take a knock. Sage subsequently announced a reorganization that included axing 40% of its workforce.
RSV immunizations became available
On May 3, the FDA approved GSK’s Arexvy, the first vaccine for respiratory syncytial virus (RSV) for use in people aged 60 and older. Before May was over, the agency also approved Pfizer’s Abrysvo, a second RSV vaccine for the same age group. On Aug. 21, Abrysvo also received the FDA’s approval for use in pregnant individuals between 32 and 36 weeks’ gestation to prevent RSV in babies from birth to 6 months of age. Both vaccines use an RSV surface protein called the fusion glycoprotein to initiate an immune response from the body. The agency green-lit a different type of RSV immunization on July 17 when it approved AstraZeneca and Sanofi’s Beyfortus (nirsevimab), a monoclonal antibody that can be given to babies and children up to 24 months in age. Moderna submitted an application to the FDA for its messenger RNA–based RSV vaccine in July. Bavarian Nordic’s vaccine, which featured a live virus decorated with RSV proteins, failed to meet all its primary end points, prompting the company to discontinue its RSV program.
A birth control pill and Narcan became available over the counter
The FDA first approved norgestrel as a prescription oral contraceptive in 1973. Fifty years later, on July 13, the agency approved Perrigo’s Opill as a version of this birth control pill that doesn’t require a prescription.
In another notable over-the-counter approval, the FDA made Narcan (naloxone), Emergent BioSolutions’ nasal spray for reversing opioid overdoses, available to consumers without a prescription on March 29. Previously, advocates had managed to work around the drug’s prescription-only status via a patchwork of state laws, standing orders, and collaborative practice agreements among pharmacists.
Lumakras study was called into question
A Phase 3 trial that was meant to confirm the data that won Amgen’s Lumakras (sotorasib) expedited approval didn’t pass muster with a panel of FDA advisers. In October, the panel voted 10–2 that the CodeBreaK 200 trial results could not be reliably interpreted.
In 2021, the FDA granted expedited approval to Lumakras to treat people who have advanced non-small-cell lung cancer driven by theKRAS G12C mutation and had previously taken another chemotherapy. Lumakras was the first drug to inhibit KRas, a notoriously challenging target.
The FDA required further data to convert its accelerated approval into full drug approval. The study that was intended to provide those data, CodeBreaK 200, showed that progression-free survival was about a month longer for people who took Lumakras compared with people who took docetaxel, a standard second-line treatment for this type of cancer. The study found no difference in overall survival.
But the FDA advisers questioned CodeBreaK 200’s results. They cited a high dropout rate among patients in the docetaxel arm of the study, which may have introduced bias. The advisers were also concerned because independent reviews of tumor imaging scans differed significantly from those conducted by the study’s investigators.
The advisory panel’s conclusion does not mean that Lumakras will be withdrawn from the market, but further studies may be needed. The FDA will make its decision on Lumakras’s full approval later this month.
Phenylephrine isn’t an effective oral decongestant, according to an FDA panel
In 2022, people in the US spent an estimated $1.8 billion on over-the-counter pills and liquids containing phenylephrine, such as DayQuil and Sudafed PE, according to manufacturer sales data compiled by the FDA. But this September, an FDA advisory panel agreed in a unanimous vote that the ingredient doesn’t work as a decongestant when taken orally.
Phenylephrine, which has been used medically since the 1930s, constricts blood vessels. The FDA has deemed it generally recognized as safe and effective, or GRASE in the agency’s parlance, for over-the-counter medications since 1976. For decades, though, scientists have argued that the FDA’s decision was based on flawed data. They say that when taken orally, phenylephrine is quickly metabolized in the gut to inactive molecules and never makes its way into the bloodstream. Nasal sprays that contain phenylephrine are still considered effective at stopping runny noses.
The drug came into widespread use in oral formulations after the US federal government enacted the Combat Methamphetamine Epidemic Act of 2005. That legislation required pharmacies to keep cold remedies with a different decongestant—pseudoephedrine, which can be easily converted to methamphetamine —behind the counter, and it required consumers to show identification to purchase them. Drugmakers used phenylephrine to fill the public’s demand for cold medicines.
The FDA panel reviewed the old data along with the results of more recent clinical trials that showed that oral phenylephrine didn’t work, even at doses higher than those recommended on the packaging. The FDA is considering the panel’s recommendation and will make the final decision about whether phenylephrine should keep its GRASE designation, but the process could take more than a year.