Bristol Myers Squibb’s February approval for CAR-T lymphoma med Breyanzi came after multiple delays that ended up costing investors in a big way. FDA documents now offer clues about what went wrong, a biotech analyst writes.
Bristol “may not have been entirely thorough” during the application and review process, Mizuho analyst Salim Syed wrote to clients Wednesday after reviewing the FDA documents.
“Applications are either complete or not—this is a very binary concept,” Syed wrote.
Early last year, the FDA accepted the company’s biologics license application and set an August 2020 decision deadline. The agency later kicked the goal date back to November 16, but it ended up missing that date as well. Breyanzi eventually scored the much-awaited FDA nod in February 2021.
While the pandemic did play a role in the med’s challenging journey through the agency, it's “not the whole story,” Syed wrote. BMS, for its part, contends that COVID-related plant inspection delays were a key reason for a missed payout to investors.
At the start of the regulatory process, FDA officials found Bristol's application to be “inadequate," Syed pointed out in his note after reviewing agency documents that go "all the way back to the beginning."
To resolve the initial problems, Bristol Myers made changes to the application that amounted to a “major amendment” at the FDA, which triggered an extension of the review, the analyst said. The FDA didn’t link the overall “inadequacy” of the original application to COVID-19, Syed wrote.
In May, Bristol disclosed that the agency had kicked its decision deadline back by three months—to November from August—to review “additional information” the company had submitted.
Later in the year, COVID-19 travel restrictions prohibited FDA inspectors from visiting a Lonza site involved in the drug’s production process, Syed wrote after parsing the documents.
Meanwhile, there were still “outstanding issues” at a Juno Therapeutics plant in Washington by the FDA’s November decision deadline, the analyst wrote. Bristol bought the CAR-T player Juno in early 2018. When BMS addressed those FDA concerns, the agency found some of its responses to be “unclear and questionable,” one document shows.
At the time of the FDA's November deadline, the company notified investors that the COVID-19 pandemic had interfered with inspection plans for a third-party plant and that the application remained pending. The FDA didn't provide a new decision deadline at the time.
Aside from being an important new cancer medicine, the drug garnered industrywide attention for its connection to Bristol’s lucrative contingent value right associated with its Celgene buyout. The medicine had to score an FDA approval by the end of 2020 as one stipulation of the $6 billion payout, so the series of setbacks ended up costing investors as the calendar turned to 2021 without an FDA nod.
BMS believes COVID-related delays were the key contributor for the missed contingent value right payout.
“We believe in the strength of our BLA filing for liso-cel and that the FDA would have been able to complete the review at the revised, extended PDUFA date (11/16/2020) within the CVR timeline had it not been for COVID-related inspection delays,” a spokesperson said.
Overall, Syed and his team found that Bristol made 96 amendments to its Breyanzi FDA application, about 50% more than the average of its CAR-T rivals—Gilead's Yescarta and Novartis’ Kymriah. Gilead made 70 amendments to its Yescarta application, while Novartis made 61 changes, Syed wrote.
In fact, BMS was addressing questions about a factory inspection as late as mid-December, FDA records show.
Now, in 2021, Bristol has scored CAR-T approvals for Breyanzi and more recently Abecma, which is approved to treat multiple myeloma patients who have tried four other therapies.