FDA About to Make Drug Approvals More Difficult
For drug producers trying to bring their lifesaving treatments to market, sky-high approval costs are a formidable, and sometimes unbeatable, foe. The cost of creating a new medication and getting it approved tops an astounding $5 billion. And now, the Food and Drug Administration (FDA) is poised to make it more difficult to get cancer medications approved. The agency is proposing to subject cancer drugs to costlier and lengthier pre-approval trials, even if there’s promising preliminary evidence that these therapeutics shrink tumors. It’s unclear if drug sponsors will even be able to recruit enough volunteers needed to run a fully randomized clinical trial, given the rarity of cancer types being treated. Policymakers and FDA officials must recognize the changing landscape of therapeutics testing. It’s critical that patients have access to game-changing medications without red tape and regulatory delay.
In announcing its new draft guidance, the FDA bemoaned small datasets and “reliance on cross-trial comparisons to historical trials to assess whether the observed treatment effect represents an improvement over available therapy...” This status-quo is admittedly not ideal. In a perfect world, researchers would be able to recruit an army of volunteers, randomly assign them medications (vs. placebos) and assess medication impacts with a high degree of certainty. This becomes difficult to pull off when about a quarter of all cancers diagnosed in the U.S. are types that afflict fewer than 40,000 people per year. As a team of researchers at the University of Rochester point out, “[b]y necessity, clinical trials in rare disorders enroll small samples. In combination with high inter-individual variability in clinical course observed in many rare diseases, this diminishes a study’s power.”
The FDA already has a poor track-record addressing these concerns. One poorly reasoned rejection centered around a medication called omburtamab, designed to treat a rare pediatric brain cancer. At first, the agency granted some leeway and allowed omburtamab’s sponsor (Y-mAbs Therapeutics) to give the drug to a small number of patients and compare survival outcomes to a historic dataset of similar patients who never had access to the drug. While impressive outcomes were reported, regulators were skeptical because the patients being given omburtamab also had access to other treatments that were out of reach for at least some of the patients in the “control group” dataset. Additionally, the dataset contained some information collected during the 1990s and early 2000s when cancer treatments may have been less effective.
The agency extensively communicated these concerns with its advisory committee, concluding that the FDA, “cannot reliably attribute the observed [overall survival] OS difference to omburtamab.” In the same analysis, though, the FDA reported that it was in fact able to control for patients’ use of other treatment (i.e., radiation therapy, surgery, chemotherapy) and the time-period of treatment. And, even after adding the controls, the results appear encouraging for the medication. The data suggests that patients taking omburtamab live 7-12 months longer than their non-medicated peers. Despite these sustained positive findings, the advisory committee bought into the FDA’s critical briefing and voted to reject the drug. The FDA followed suit and sent Y-mAbs a rejection letter.
If the FDA’s draft guidance becomes agency policy, far more medications such as omburtamab will be rejected and the use of historic data will effectively be banished. This would further slow down FDA approvals, which were already 25 percent lower in 2022 than 2021.
The agency must reverse course and commit to a faster, more flexible approvals process. Patients need all the tools they can get to fight deadly, unrelenting diseases.
David Williams is the president of the Taxpayers Protection Alliance.
