November 16, 2023
I’m Sophia Phillips, a health policy associate at the National Center for Health Research. Our scientists and health professionals scrutinize the safety and effectiveness of medical products, and we don’t accept funding from companies that make those products, therefore I have no conflicts of interest.
We thank all of you for participating in this meeting to publicly scrutinize the dangling accelerated approvals of pralatrexate and belinostat. Confirmatory trials for drugs granted accelerated approval are too often delayed for years and are later shown to fail to demonstrate meaningful, patient-centered outcomes. Meanwhile, the drug remains on the market and patients are paying for drugs that are not proven to benefit them. This is particularly unacceptable for these 2 drugs, for which the sponsor does not expect to complete confirmatory trials for 7 more years in addition to the 14 years and 9 years that the drugs have already been on the market without clear evidence of a clinically meaningful benefit.
Oncology drugs account for more than 60% of all accelerated approval drugs and we can all agree that the public has a right to question the lack of evidence regarding the benefits of these drugs. Research indicates that as of 2019, only 20% of cancer drug indications approved through the accelerated approval pathway from 1992-2017 demonstrated improvements in patients’ overall survival based on their confirmatory trial data. Our Center’s research also found no evidence of improved quality of life in most confirmatory trials.
In an analysis of 100 accelerated approval confirmatory trials completed or due between 2012 and 2021, more than half were past their expected completion deadline set by the FDA. Both pralatrexate and belinostat fall in that category, as I previously stated it has been more than 14 years and more than 9 years since they were awarded accelerated approval respectively. The FDA has stated that “an appropriate target completion date for oncology products would ideally be no later than 2-4 years after accelerated approval is granted.” Further, we agree with FDA that the reasons provided by the sponsor for the delay of these trials are not sufficient justification for these very long delays. So why are these products allowed to remain on the market? This delay is not fair to patients, most of whom assume these drugs are proven to have benefits that outweigh the risks.
Unfortunately, in addition to clinical uncertainty about the benefits of these drugs, they often have serious adverse effects that result in high rates of discontinuation. For example, nearly 50% of patients taking belinostat experienced a serious AE; this includes the 10% that experienced cardiac related adverse effects and two patients with cardiac failure. In addition to neither drug being well-tolerated by patients, these drugs are very expensive. Each cost hundreds of thousands of dollars annually, adding to the overall burden faced by cancer patients and taxpayers.
There are significant concerns in the accelerated approval program that must be addressed:
- The long delay before confirmatory trials are completed and made public;
- The lack of meaningful clinical data provided in confirmatory trials, which often continue to rely on unproven surrogate endpoints;
- and additional delays that keep drugs on the market even when confirmatory trials fail to confirm that the drugs are safe and effective.
As a result of these issues, patients have been harmed by unproven products remaining on the market. We urge the FDA to hold this sponsor, and others, accountable for their failure to conduct confirmatory trials in a reasonable timeline. While we support the new effort by the FDA to require confirmatory trials to start prior to granting an accelerated approval, that does not affect these two drugs — and in the future it does not provide an incentive for sponsors to complete confirmatory trials in a timely manner. As soon as a drug is approved many study participants will drop out of trials due to fear of being placed in the placebo group, unless the sponsor completes the trial quickly.
In conclusion, when sponsors exploit the flexibilities granted by the FDA, as happened with this sponsor, we believe it necessary for FDA to rescind approval until a trial is completed that confirms meaningful clinical benefits.
Thank you.