When Bristol Myers Squibb bought out Celgene for $74 billion back in late 2019, one of the purported centerpieces in that deal was liso-cel, which hoped to join a small group of CAR-Ts for non-Hodgkin lymphoma. Expecting an approval in 2020, Bristol has had its share of setbacks in getting liso-cel across the finish line — but now it finally has the green light.
The FDA on Friday approved Bristol’s Breyanzi (lisocabtagene maraleucel), a CAR-T to treat diffuse large B cell lymphoma in patients who have previously received two prior rounds of systemic therapy, the agency said in a release.
The agency based its review on pivotal Phase I data showing 54% of patients treated with liso-cel achieve complete remission. DLBCL makes up about 33% of all non-Hodgkin lymphoma cases, the FDA said, of which there are around 77,000 newly diagnosed each year.
With the approval will come a black-box warning label for both cytokine release syndrome, a potentially fatal overreaction of the immune system, as well as neurologic toxicities. Those warnings are severe enough that the FDA has instituted a Risk Evaluation and Mitigation Strategy that will require healthcare facilities and physicians administering the therapy to be specially certified to identify and treat CRS and neuro toxicities.
Those warnings and administration restrictions are aren’t unique to liso-cel, however. Gilead’s Yescarta and Novartis’ Kymriah, for instance, sport the same black box warnings, and the unmet clinical need will likely drive uptake in what is an extremely difficult-to-treat patient population.
Liso-cel is now the third CAR-T on the market for various forms of non-Hodgkin lymphoma, alongside Yescarta and Kymriah. Bristol aimed to have the therapy approved late last year, but delays from Covid-19 and an ugly inspection report at one of the company’s contract manufacturing sites pushed the approval into the new year.
Liso-cel was one of a group of pipeline candidates tied to a $9 CVR from Bristol’s Celgene buyout in 2019. With the approval delay, investors lost out on that payday when the year expired — not a major issue for Bristol itself but definitely a headache for the CVR traders.
In December, an FDA inspection at Lonza Houston’s plant found a raft of issues, including mislabeling, products for the US and EU drug markets stored in the same bins, “poorly maintained” freezer units, and expired batches of ingredients that weren’t properly disposed of, according to a Form 483 letter published online late last month.
Lonza, one of a group of contractors working on liso-cel’s manufacturing, said delays in the FDA’s inspection schedule made it difficult to adjust in time for an approval within 2020. Bristol previously said it responded to the agency’s concerns within eight days of receiving its letter.