Everyone should be able to get the prescription drugs they need at a price they can afford. But a new study from JAMA Internal Medicine highlights a hard fact: Americans are paying for some drugs that have insufficient proof of effectiveness. While dozens of oral cancer medications received approval through the U.S. Food and Drug Administration’s (FDA) accelerated pathway from 2011 through 2018, very few pharmaceutical manufacturers actually followed through to provide data demonstrating that their medication works. Now, as Congress begins to consider Cures 2.0 and FDA User Fee Act renewals, they must strengthen enforcement powers and hold both the FDA and drug manufacturers accountable.
The FDA’s accelerated approval pathway authorizes certain drugs’ approval if preliminary research suggests it will be effective in treating conditions for which there are few (if any) medications available. This approval is conditional, however. Manufacturers are required to conduct post-approval studies to “verify the anticipated clinical benefit.” The accelerated approval pathway is an important tool and has led to the availability of more than 100 drugs that ultimately proved effective through post-market studies, granting patients access to new and innovative therapies and treatments.
As the JAMA study and others show however, FDA and manufacturers are not always following through on meeting these obligations to complete additional validation research, and some drugmakers may be viewing the accelerated approval pathway as a means to circumvent the normal drug approval process. In the wake of the FDA’s approval of Alzheimer’s medication Aduhelm through this accelerated pathway, it is clear this process has become an issue of serious concern. In the meantime, patients are left paying the price – both financially, and potentially in their health and well-being as well.
The JAMA study looks at 44 new oral targeted cancer drugs that were dispensed between 2011 and 2018. Across the study period, those receiving drugs without documented overall survival benefit increased from 13% in 2011 to 59% in 2018. Cumulative spending on the new oral cancer drugs without documented overall survival benefit totaled $1.8 billion (51.6% of all spending on the new drugs) by the end of 2018. Only 11 of the 44 drugs (25%) had documented, statistically significant overall survival benefit under their FDA approvals. Only 4 had studies with survival as a primary endpoint.
Other studies are finding the same trend. In a review of FDA data, researchers publishing in The BMJ examined drugs approved via an accelerated pathway. Of the 253 drugs approved through an accelerated pathway since 1992, 112 have not been confirmed as clinically effective. A mere 6 of 24 drugmakers contacted as part of the study reported conducting the necessary follow-up study within 5 years of approval.
This is the same avenue through which Aduhelm was controversially approved, with FDA requiring the manufacturer continue to investigate it while allowing the drug to be used. In the case of Aduhelm, concerns over the lack of evidence of the drug’s effectiveness were further reinforced when none of FDA’s advisory committee experts voted for its approval even through the accelerated pathway’s more flexible standards. Aduhelm also presents significant safety concerns. The independent Institute for Clinical and Economic Review (ICER) found that 35% of clinical trial participants suffered from symptoms and side effects including headaches, confusion, dizziness, and bleeding in the brain. Despite these concerns, FDA is allowing the manufacturer up to 9 years to complete their follow-up research to prove whether the drug is safe and effective in the treatment of Alzheimer’s disease.
While accelerated approval comes with the understanding that the FDA will remove any drug from the market that does not prove effective or is found to be unsafe, few drugs actually are withdrawn from the market after falling flat in post-market studies. One of those few cases was the cancer-fighting drug Keytruda, whose manufacturer “voluntarily” pulled the drug from the market as a treatment for lung cancer following both a failed trial and FDA’s announced crackdown on drugs that fail to meet post-market approval requirements. This example shows how the accelerated approval process should work, and Congress needs to ensure this practice becomes the norm and not the exception. Unfortunately, the FDA is failing to consistently enforce the terms which require follow-up studies of drugs approved under the accelerated pathway.
These drugs come at a massive price for both payers and society. Drugs that have not been fully vetted or are outwardly ineffective cost Americans billions of dollars, without delivering the effective, safe care they deserve.
We need to fix the accelerated approval pathway. Drug manufacturers should not be allowed to game the system to keep unproven drugs on the market while ignoring their responsibilities to protect patients and hardworking American families.