As the pace of accelerated approvals has increased over the past few years, and as the number of withdrawals of accelerated approvals for some indications and products has also increased, the latest FDA move to seek removal of Makena, the premature birth preventative, for lack of efficacy could spell trouble for firms that cannot demonstrate safety and effectiveness of their products in confirmatory studies.

Most often, drugs that are granted accelerated approval are based on a surrogate endpoint that is anticipated to translate into efficacy for the proposed indication.  The FDA approval is usually based on a single study using the surrogate endpoint in a treatment for which there is an unmet medical need.  On this, FDA says that “a surrogate endpoint is a marker, such as a laboratory measurement, radiographic image, physical sign or other measure that is thought to predict clinical benefit but is not itself a measure of clinical benefit.”  Using a surrogate endpoint can “significantly shorten the time to approval of a product” but firms are still required to submit clinical studies “to confirm the anticipated clinical benefit.”

The FDA been stuck between a rock and a hard place for years by the call to bring promising drugs to market more quickly to treat unmet medical needs.  The recent approval of an Alzheimer’s drug and a drug for ALS speaks to the FDA’s dilemma.  What can you do for patients who have either no or few options for treatment?  The accelerated approval process grew out of the answer to that question.

The criticism of the accelerated approval program is that patients may be receiving a drug that has not been proven to actually work.  One of the big issues, of course, is that the confirmatory trials can take
3-10 years to complete with no guarantee that the results will be positive.  During that period of time, patients, insurers, and government programs are laying out millions of dollars for a drug that might not be effective.  This dilemma is inherent in the program, but when a confirmatory trial fails, the path forward is fairly clear.  The Advisory Committee recommendation to the FDA yesterday in a vote of 14-1 to remove the product from the market certainly provides the FDA with a position it will likely take seriously.

We know that the FDA does not have to take the advice of its Advisory committee but given the tone and FDA stance at the meeting, as well as the pre-meeting information publicly published on FDA’s website in anticipation of the meeting, it appears that the outcome may not be in doubt.  How this will impact others seeking to use the accelerated approval process and how the FDA will grant access to the accelerated approval process in the future is not known, but there seems to be a bit of a chill in the fall air regarding the process in general.  There were proposed revisions to the accelerated approval process proposed in the User Fee reauthorization but those provisions were stripped from the proposed bill to assure the must approve User Fee legislation was approved in a timely manner.  That dialogue is continuing and it is anticipated that changes to the accelerated approval program will be taken up in the final appropriations bill set to be dealt with in December.