Bris­tol My­ers Squibb earns long-await­ed FDA nod for liso-cel, join­ing short list of lym­phoma CAR-T win­ners

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.

The one-time ther­a­py will come with a $410,300 whole­sale price, Bris­tol said, say­ing it came up with that fig­ure af­ter con­sid­er­ing “many fac­tors in­clud­ing its med­ical and clin­i­cal val­ue, pa­tient val­ue and so­ci­etal val­ue.”

That’s a sig­nif­i­cant pre­mi­um over Gilead’s Yescar­ta, which launched with a $373,000. Kym­ri­ah al­so launched with a $373,000 WAC for B cell lym­phomas.

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. Yescar­ta and 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.

2023 Spot­light on the Fu­ture of Drug De­vel­op­ment for Small and Mid-Sized Biotechs

In the context of today’s global economic environment, there is an increasing need to work smarter, faster and leaner across all facets of the life sciences industry.  This is particularly true for small and mid-sized biotech companies, many of which are facing declining valuations and competing for increasingly limited funding to propel their science forward.  It is important to recognize that within this framework, many of these smaller companies already find themselves resource-challenged to design and manage clinical studies themselves because they don’t have large teams or in-house experts in navigating the various aspects of the drug development journey. This can be particularly challenging for the most complex and difficult to treat diseases where no previous pathway exists and patients are urgently awaiting breakthroughs.

Kristen Hege, Bristol Myers Squibb SVP, early clinical development, oncology/hematology and cell therapy (Illustration: Assistant Editor Kathy Wong for Endpoints News)

Q&A: Bris­tol My­er­s' Kris­ten Hege on cell ther­a­py, can­cer pa­tients and men­tor­ing the next gen­er­a­tion

Kristen Hege leads Bristol Myers Squibb’s early oncology discovery program carrying on from the same work at Celgene, which was acquired by BMS in 2019. She’s known for her early work in CAR-T, having pioneered the first CAR-T cell trial for solid tumors more than 25 years ago.

However, the eminent physician-scientist is more than just a drug developer mastermind. She’s also a practicing physician, mother to two young women, an avid backpacker and intersecting all those interests — a champion of young women and people of color in STEM and life sciences.

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Spe­cial re­port 2022: Meet 20 women blaz­ing trails in bio­phar­ma R&D

When you run a special report for a fourth year, it can start feeling a little bit like a ritual. You go through the motions — in our case opening up nominations for top women in biopharma R&D and reviewing more than 500 entries — you make your choices of inclusion and exclusion. You host a ceremony.

But then things happen that remind you why you do it in the first place. Perhaps a Supreme Court rules to overturn the constitutional right to abortion and a group of women biotech leaders makes it clear they strongly dissent; perhaps new data on gender diversity in the industry come out that look all too similar to the old ones, suggesting women are still dramatically underrepresented at the top; perhaps protests and conflicts around the world put in stark terms the struggles that many women still face in earning the most basic recognition.

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Phar­ma rep­u­ta­tion re­tains 'halo' even as pan­dem­ic me­dia cov­er­age re­cedes — sur­vey

The Covid-19 halo effect on the pharma industry is continuing, according to a new global study from Ipsos. The annual survey for the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) finds considerable goodwill from consumers across measures of trust, cooperation with governments, and advancing research and drug development.

“Despite the pandemic in many countries no longer being the top of mind concern generally – although it does remain the top concern as a health issue – the industry’s reputation has remained positive,” said Ipsos research director Thomas Fife-Schaw.

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FDA commissioner Robert Califf (Jose Luis Magana/AP Images)

FDA pulls On­copep­tides' Pepax­to in­di­ca­tion, open­ing the door for dan­gling ac­cel­er­at­ed ap­proval en­force­ment

In a move all but ensured after an overwhelmingly negative adcomm vote this September, the FDA is yanking Oncopeptides’ dangling accelerated approval. And there may be more to come.

In recent months, US regulators have honed in on reforming the accelerated approval pathway and preventing drugmakers from continuing to sell their medicines in the event of a confirmatory study flop. The moves come after commissioner Rob Califf has called for companies to do more to produce post-marketing evidence quickly earlier this year.

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Gossamer Bio CEO Faheem Hasnain at Endpoints' #BIO22 panel (J.T. MacMillan Photography for Endpoints News)

Gos­samer’s Fa­heem Has­nain de­fends a round of pos­i­tive PAH da­ta as a clear win. But can these PhII re­sults stand up to scruti­ny?

Gossamer Bio $GOSS posted a statistically significant improvement for its primary endpoint in the key Phase II TORREY trial for lead drug seralutinib on Tuesday morning. But CEO Faheem Hasnain has some explaining to do on the important secondary of the crucial six-minute walk distance test — which will be the primary endpoint in Phase III — as the data on both endpoints fell short of expectations, missing one analyst’s bar on even modest success.

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Prometheus moves to raise cash hours af­ter PhII da­ta leads to stock surge

After releasing better-than-anticipated data on two mid-stage studies Wednesday morning, Prometheus Biosciences’ CEO said the company would “take some time to assess” its next financing options.

It only needed about seven hours. Wednesday afternoon after the market closed, the biotech announced it would seek $250 million through an equity offering as the company looks to edge out anti-TL1A competitor Pfizer and its new partner Roivant.

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Enhertu researcher Ian Krop speaks during Wednesday's SABCS press conference (MedMeetingImages/Todd Buchanan via SABCS)

SABCS roundup: No­var­tis shows two-year PFS in breast can­cer sub­groups; As­traZeneca re­veals more En­her­tu da­ta

The San Antonio Breast Cancer Symposium is taking place this week, and so far, some of the Big Pharmas are turning out new trial data about some of the biggest drugs in the space.

First off, Novartis announced that its drug, Kisqali, showed about a year of progression-free survival in patients with different types of first-line metastatic breast cancer. The CDK 4/6 drug was first approved by the FDA in 2017, setting it up in direct competition against Pfizer’s Ibrance.

Big Phar­mas team up with lo­cal Sin­ga­pore or­ga­ni­za­tions to boost man­u­fac­tur­ing

Singapore has long established itself as a major hub for pharma manufacturing, and now several big players are looking to further cement their presence in the Lion City.

Takeda, Sanofi and GSK are forming a partnership with the Singapore-based Agency for Science, Technology and Research (A*STAR) and several local academic institutions, including the National University of Singapore, Nanyang Technological University, Singapore, its enterprise company called NTUitive and Singapore Institute of Technology to provide a greater boost to the manufacturing of biologics.