As COVID disrupts FDA inspections, will liso-cel approval be further delayed?

Coronavirus-related constraints mean the US FDA has not yet inspected manufacturing facilities in Washington and Texas, risking a delay in the approval of Bristol-Myers Squibb’s lymphoma CAR-T candidate liso-cel.

Bristol-Myers Squibb added anti-CD19 targeting lymphoma candidate lisocabtagene maraleucel (liso-cel) to its pipeline through the $74 billion acquisition of Celgene.

In May, the action date of the Biologics License Application (BLA) for the chimeric antigen receptor (CAR) T-cell therapy was extended by three months by the US Food and Drug Administration (FDA). But now the new PDUFA date of November 16 2020 is at risk due to constraints within the FDA’s inspection team, senior management said this week.

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Referencing an SEC 10-Q filing, chief medical officer Samit Hirawat said the firm disclosed at the beginning of August that certain site inspections relating to the review of liso-cel have not yet occurred and with the impact of COVID-19 the FDA continues to be hampered in visiting the firm’s manufacturing facilities, risking a potential November approval.

“With the evolution of the COVID-19 as well as the challenges it has posed both for us and for the FDA, it does pose a risk because the FDA staff – like many of us – are operating under those significant constraints on travel because of COVID,” he told analysts at the Citi 15th Annual Biopharma Conference.

“While we typically don’t provide any details on regulatory discussions, what I can say today is the FDA has informed us that they will require inspection of both our facilities in Washington state as well as the manufacturing organization for the vector, which is located in Texas.”

The Bothell, Washington site was added to Celgene when the firm acquired Juno Therapeutics in 2018, and subsequently is now part of Bristol-Myers Squibb. The Texas-based facility is run by a contract development and manufacturing organization (CDMO) though Bristol-Myers Squibb – and Celgene and Juno before it – has not divulged the partner.

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Some of the FDA staff working on liso-cel are likely to be “pulled into the inspection related activities that might be coming along for the COVID related vaccines,” Hirawat continued. “Now, FDA is very well aware of that. They are juggling multiple things as this is a public health crisis and they need to manage as well as the diseases that are life threatening, they also need to manage that. So, those are all running in parallel. I don’t think we can say anything more except that the importance of this application is very, very high for us.”

He added the firm is working very closely with the FDA to keep the application on track but reiterated that the Agency “will require the inspection of facilities” before a decision is made, implying the November date is optimistic at best.

FDA approval of liso-cel by December 31, 2020 is one of the required remaining milestones of the Contingent Value Rights issued upon the close of the Celgene acquisition late last year. Another is FDA approval of Idecabtagene Vicleucel (ide-cel) by March 31 2021, though that program has already suffered a setback with the FDA refusing to file a BLA in May due to a lack of manufacturing information.

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