Fewer innovative treatments are becoming available to patients, and fewer still will be developed in the first place.
In 2018, the FDA approved 59 novel drugs for patient use, the highest yearly number in history. In 2023, the FDA’s Center for Drug Evaluation and Research approved 55 new drugs, the second-highest number ever. Last year, it approved an even 50, in line with a seeming new standard in which (apart from a Covid-era dip in 2022) annual approvals since 2018 had been running at around 50 or more, significantly higher than in previous years. It had been expected that the post-pandemic bounce would see another strong number for 2025, but that now does not seem likely. As of August 29, the agency has green-lighted just 26 drugs so far. That means it’s on pace to approve just 39 drugs this year — a startling drop-off.
These numbers can feel abstract, so it’s helpful to get some stories of real, potentially life-saving treatments that patients are desperately waiting to try. In a recent article, the Wall Street Journal’s editorial board provides some examples. One such is a drug developed by biotech company Replimune, which has been designed as a treatment for patients with advanced melanoma, of whom only 22.5 percent can expect to survive for five years. This was rejected last month, although, as the WSJ’s editorial board relates:
About a third of patients who hadn’t responded to prior immunotherapy showed a strong response to Replimune’s [drug] in a clinical trial.
Tumors shrank in nearly all patients, and responses proved durable over three years. Serious side effects were rare. Oncologists who treated patients in the trial hailed the results. Yet the FDA said the trial was “not considered to be an adequate and well-controlled clinical investigation that provides substantial evidence of effectiveness.”
Regulators took issue with Replimune’s clinical trial because it lacked a control group. The WSJ’s editorial board notes that “Vinay Prasad, the head of the [FDA’s] biologics division [who was first appointed this year], has long criticized such single-arm studies that have no placebo groups. He believes medicines should undergo randomized controlled trials that track patients over longer periods to measure overall survival.”
Put in simpler language, Prasad wants to include placebos as part of the testing process, but doing that in cases such as this means that some melanoma patients would be denied access to the drug that could prolong or save their lives. Those patients signed up for a clinical trial, choosing to run the risk of taking an unapproved drug because of the chance it offered of effective treatment. Essentially denying those patients “treated” with the placebo the chance of survival offered by a new drug is, to say the least, cruel.
Another drug trapped in the FDA’s approval process was developed by Stealth BioTherapeutics to treat Barth syndrome, which, as is explained in the WSJ’s report, “causes a fatal weakening of the heart, muscles and immune system and afflicts about 150 Americans.” Many born with this rare genetic condition die in their earliest years. Those who survive childhood have a life expectancy of under 50.
The WSJ:
Stealth applied for approval in January 2024, and an FDA advisory committee last autumn found the drug to be effective. But the agency keeps changing its demands and has deployed one excuse after another to delay approval. The agency recently told Stealth to resubmit its application, which would take at least six months to review.
Stealth CEO Reenie McCarthy says her company might not survive that long. If the company fails, patients that began receiving the medicine in the trial will lose access, and others may never benefit. Parents of children in Stealth’s trial are urging the FDA to approve it. So are Democrats and Republicans in Congress.
The immediate effects of the FDA’s sudden roadblock are terrible, but the long-term implications could be worse. Pharmaceutical and biotech companies rely on a clear, predictable pathway for their drug candidates to be reviewed. For the FDA to change its rules on the fly and push approval timelines way back undoubtedly disincentivizes innovation. The first drugs to drop out of their pipelines are likely to be those that target rare diseases, where the risk/reward ratio is at its most unforgiving.
Donald Trump’s FDA commissioner is Dr. Marty Makary. Earlier this year, Makary pledged to accelerate drug approvals at the agency, especially for life-threatening and rare diseases. He was echoing decades of conservative calls to streamline the FDA’s regulatory process, granting access to more treatments at a faster pace to save additional lives, a superficially less cautious approach than that advocated by many progressives. The conservative response has been that, while the FDA should ensure a baseline level of safety, more of the assessment of a drug’s risk and efficacy should be performed by the patients’ doctors, in coordination with their insurance companies and, of course, with the patients themselves.
This does not appear to be a view shared by Dr. Prasad, a progressive ally of Robert F. Kennedy Jr., who runs the health and human services department that oversees the FDA. We cannot know for sure what lies behind the stalled drug approvals, but it’s quite reasonable to think that Kennedy’s influence bears a good portion of the blame.