Millions of patients across the country have urged the Food and Drug Administration (FDA) to be more proactive in approving life-saving medications. But, to some pundits, the FDA is actually being too lenient in approving drugs. According to a recent analysis published in Bloomberg, “Americans are spending billions [of dollars] on drugs that don’t work” because of the FDA’s “drive to get new drugs to patients quickly — sometimes even before they’re done testing.”
The commentators cite numerous examples of drugs being green-lit too quickly under accelerated agency approval programs, only to be withdrawn when efficacy evidence doesn’t pan out. Unfortunately, the writers ignore the larger context of FDA accelerated approvals and fail to focus on the agency’s continued risk aversion. The FDA cannot be reformed without reining in its culture of rigidity and rejection.
The Bloomberg piece points to oncology drugs such as Lartruvo, Ukoniq and Zydelig, which snagged preliminary approvals based on early, promising small-scale evidence. Generally, the FDA has pursued a lower standard of evidence in getting drugs to market quickly if they target a disease with few existing treatment options. Drug sponsors and the FDA have wide latitude to get these drugs removed from the market if subsequent studies fail to find effectiveness, and that’s exactly what happened in the cases cited by Bloomberg.
The reporters take issue with the money (and patient hope) wasted on these drugs and the enrichment of drug sponsors in between approval and withdrawal of these medications. But, the cases they cite are far from typical. According to a 2022 study published in the journal “Therapeutic Innovation & Regulatory Science,” only 14 out of 167 (8.4%) medications granted accelerated approvals by the FDA between 2012 and 2021 were withdrawn from the market. Far more medications (51) were ultimately granted approval by the agency following large-scale evidence confirming the medications’ clinical benefits. The study authors conclude, “the accelerated approval program has been largely successful. … Recent FDA actions show that the agency is appropriately managing the program when a drug approved under accelerated approval fails to confirm a clinical benefit.”
The problem is not with accelerated approvals. Rather, the FDA is rejecting too many life-saving drugs. The agency has issued more than 80 Complete Response Letters (i.e., denials) for new molecular or biologic products since 2019, often for reasons that have little to do with clinical benefit. For example, the FDA recently rejected a drug called zolbetuximab designed to treat gastric/ gastroesophageal cancer. The issue was neither safety nor efficacy. Clinical trials demonstrated that the medication improved median progression-free and overall survival by 2-3 months compared to chemotherapy alone. It appears, instead, that the issue boiled down to “unresolved deficiencies following its pre-license inspection of a third-party manufacturing facility.” These issues clearly aren’t insurmountable for Japanese regulators, who approved the medication. But, in the U.S., patients are left to scramble for months due to a likely minor issue that could probably be resolved post-approval.
Another poorly reasoned rejection centered around a medication called omburtamab, designed to treat a rare pediatric brain cancer. Agency officials expressed concern that the datasets used to study the drug were too old to be reliably interpreted, even though the FDA acknowledged that, according to the evidence, patients taking omburtamab live 7-12 months longer than their non-medicated peers. As TPA’s 2023 report on drug approvals points out, omburtamab and zolbetuximab are hardly the only drugs to get this treatment.
The FDA should more critically examine the reasons for rejecting these lifesaving drugs, and strive for more holistic assessments of promising medications. Contrary to recent reporting, America’s drug regulator still has a risk aversion problem.
David Williams (X: @tpapres) is the president of the Taxpayers Protection Alliance.
