, including a public list detailing cases where accelerated approvals have been rescinded for lack of evidence.
On Oct. 29, the Food and Drug Administration posted new websites detailing the status of oncology medicines given these special clearances:
- Ongoing | Cancer Accelerated Approvals
- Verified Clinical Benefit | Cancer Accelerated Approvals
- Withdrawn | Cancer Accelerated Approvals
The FDA’s cancer center also has created a web page called Project Confirm to provide more information on the way it uses accelerated approvals.
There has been increased concern about medicines cleared by accelerated approvals in recent years, culminating in an uproar over the controversial June approval of aducanumab (Aduhelm) for Alzheimer’s disease. This drew more attention to a debate already underway about how much data supports some of the indications for some cancer drugs.
Federal and state officials and advisers are putting more pressure on pharmaceutical companies to prove that medicines that are put on the market through accelerated approval do deliver meaningful benefits for patients.
In addition, earlier this month two of the top health advisers in Barack Obama’s administration proposed a new model through which Medicare could reduce payments for certain cancer drugs cleared through accelerated approvals – and even cut off reimbursements in cases where companies fail to deliver confirmatory evidence for expected benefits.
This “Pay for Drugs That Work Model” was proposed by Richard Frank, PhD, and Ezekiel Emanuel, MD, PhD, in a recent JAMA article. In their view, the FDA’s accelerated drug approval process allows for too many delays in obtaining answers as to whether medicines cleared this way provide expected benefits.
“The proposed Pay for Drugs That Work model could test a modified approach for incentivizing rapid completion of confirmatory trials to inform clinicians and patients about the true risks and benefits of new drugs and improve the value for money of cancer drugs that receive accelerated approval,” they wrote.
Excel files, regular updates
For the FDA, accelerated approvals require balancing an estimated potential benefit for people facing serious diseases (for example, cancer) against serious risks, including potentially exposing patients to costly, toxic drugs that will later be shown not to work for their conditions.
For many years, there has been significant pressure on the FDA to lean toward speedier approvals, with members of Congress, advocacy groups, and drugmakers advocating for broad use of surrogate data in deciding on clearances. The FDA posts biannual reports on its website that highlight how quickly approvals have been granted. But these biannual reports don’t provide much information on the status of accelerated-approval drugs, other than to say if they have been given full approval or withdrawn.
The newly created websites from the FDA’s oncology division appear to reflect growing public interest in knowing what standards the agency sets for confirmatory trials and what deadlines companies face to deliver evidence of significant benefit for their drugs.
The new sortable websites also include details on trials and have links to Excel files which will help researchers and others seeking to track patterns with accelerated approvals. The FDA said in an interview that it intends to update these sites when there are developments with accelerated approvals for cancer drugs, such as new clearances of this type, conversions to regular approvals, and withdrawn approvals.
Julia Beaver, MD, chief of medical oncology at the FDA’s Oncology Center of Excellence, and acting deputy director of the Office of Oncologic Diseases of the FDA’s Center for Drug Evaluation and Research, described the new websites as part of a “commitment to preserve the integrity” of the accelerated approval program.
“These new web pages will make information on our accelerated approvals more transparent,” Dr. Beaver said in an email to this news organization.
The FDA has been able to speed many medicines to market and clear additional uses for drugs already sold through the program, giving people earlier access in many cases to critical medicines, Dr. Beaver said.
More than 165 oncology indications have received accelerated approval, with almost half converted to regular approval in a median of 3 years. Less than 10% of these indications were withdrawn, Dr. Beaver said.
“Of those accelerated approvals that were converted to regular approval, many demonstrated survival advantages to patients with several types of cancer or provided meaningful therapeutic options where none previously existed,” she said.
However, Dr. Beaver also has made public the FDA’s concerns with what she and Richard Pazdur, MD, director of the Oncology Center of Excellence, have described as “dangling” accelerated approvals.
These are cases where the required trials did not end up confirming benefit for a medicine, yet the manufacturer did not move to withdraw an accelerated approval. The FDA’s cancer center has already announced that it is doing an “industry-wide evaluation of accelerated approvals in oncology in which confirmatory trials did not confirm clinical benefit.”
This stems in part from what can be called the FDA’s “growing pains” in its efforts to manage the rapidly changing landscape for these immunotherapy checkpoint inhibitors. This field of medicine has experienced an “unprecedented level of drug development” in recent years, FDA officials said in briefing materials for an Oncologic Drugs Advisory Committee (ODAC) meeting last April on dangling accelerated approvals.
A newly posted chart on withdrawn oncology accelerated approvals, posted by the FDA’s cancer division, makes it clear that the pace of these rescinded clearances has picked up. The chart lists a total 14 withdrawn indications of oncology accelerated approvals.
Six of these withdrawals happened this year.
There were two withdrawals in 2020, including the December withdrawal of nivolumab, (Opdivo) for a form of metastatic lung cancer.
Then there was a significant gap, with no withdrawals going back to 2013 (when there was one). There were two withdrawals in 2012 and three in 2011.
A version of this article first appeared on Medscape.com.