Accelerated approval of oncology drug withdrawals in 'acceleration'

Established in 1992 in response to the HIV/AIDS crisis, the FDA's Accelerated Approval policy is now used by the FDA to expedite the approval of drugs in several disease areas

The program was codified in 2012 under the Food and Drug Safety and Innovation Act (FDASIA)

Since 1992, most accelerated approvals have been for oncology and hematology indications, leading to an average of 3.

According to the author's statistics, as of December 31, 2021, the FDA has approved a total of 278 accelerated approval applications, of which 167 are oncology drugs, accounting for 60%

Among the 167 indications for accelerated approval of oncology drugs, 66 are undergoing confirmatory trials, 83 have been finalized and 83 have been approved by the FDA, and 18 have been withdrawn

FDA Accelerates Approval of Oncology Drugs

Among the FDA's accelerated approval of oncology drugs, PD1 drugs are undoubtedly the biggest beneficiaries

Merck's Keytruda (pembrolizumab) and Bristol-Myers Squibb's Opdivo (nivolumab) have received FDA accelerated approvals for 17 and 11 indications, respectively, far ahead and the top two

Novartis' Gleevec (imatinib mesylate) also has six indications for accelerated FDA approval, followed closely

But coincidentally: Keytruda and Opdivo both have 2 accelerated approval indications withdrawn, and 5 accelerated approval indications are undergoing post-approval confirmatory clinical trials

And Gleevec's 6 accelerated approval indications are all "positive" (completed post-marketing confirmatory trials and received final FDA approval)

Of course, accelerated approval of a drug needs to be withdrawn (either voluntarily by the company or by the FDA after a public hearing) if the drug's post-market confirmatory trials do not demonstrate clinical benefit

Since last year, the withdrawal of accelerated approval of PD(L)1 drugs has attracted much attention

In June last year, the FDA accelerated the approval of Biogen's new Alzheimer's drug Aduhelm (aducanumab, trade name), which made the FDA's accelerated approval policy subject to widespread controversy, including clinical experts

FDA expedited approval of oncology drug indication withdrawal 'accelerated'

It is undeniable that, at the same time, there has been a trend of “acceleration” (including the number of withdrawals and the withdrawal time after accelerated approval) for the withdrawal of oncology drug indications that have been accelerated by the FDA in recent years

Among the withdrawal events of FDA accelerated approval of oncology drugs, the earliest accelerated approval was Celebrex (celecoxib) of Upjohn (Pfizer), which was approved by the FDA on December 23, 1999 as a routine adjuvant method to reduce adenomas in patients with familial adenomatous polyposis The number of sexual colorectal polyps

The earliest indication for the withdrawal of accelerated approval was Genentech (Roche) Avastin (bevacizumab) in combination with paclitaxel in patients with metastatic HER2-negative breast cancer who had not received chemotherapy.

Interestingly, Keytruda's indication for metastatic small cell lung cancer (SCLC) with disease progression after platinum-based chemotherapy and at least one other prior therapy received accelerated approval from the FDA on June 17, 2019, in 2021.
It was withdrawn by the company on March 30, thus creating a record of the shortest time from FDA accelerated approval to withdrawal of an oncology drug, which was only 21.
4 months
.

In conclusion, among the withdrawal events of FDA accelerated approval of oncology drug indications, there were 6 drug indications approved before 2010 (1999-2010), which doubled to 12 after 2011 (2011-2021).

.
The average time from accelerated approval to withdrawal for the former is 97.
2 months, while the average time for the latter has been shortened to 55.
0 months
.

It should be pointed out that there are currently 66 confirmatory trials underway for accelerated approval indications in oncology drugs, and not every one of them will be successful and become the final lucky one!