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.

Health­care Dis­par­i­ties and Sick­le Cell Dis­ease

In the complicated U.S. healthcare system, navigating a serious illness such as cancer or heart disease can be remarkably challenging for patients and caregivers. When that illness is classified as a rare disease, those challenges can become even more acute. And when that rare disease occurs in a population that experiences health disparities, such as people with sickle cell disease (SCD) who are primarily Black and Latino, challenges can become almost insurmountable.

FDA hands ac­cel­er­at­ed nod to Seagen, Gen­mab's so­lo ADC in cer­vi­cal can­cer, but com­bo stud­ies look even more promis­ing

Biopharma’s resident antibody-drug conjugate expert Seagen has scored a clutch of oncology approvals in recent years, finding gold in what are known as “third-gen” ADCs. Now, another of their partnered conjugates is ready for prime time.

The FDA on Monday handed an accelerated approval to Seagen and Genmab’s Tivdak (tisotumab vedotin-tftv, or “TV”) in second-line patients with recurrent or metastatic cervical cancer who previously progressed after chemotherapy rather than PD-(L)1 systemic therapy, the companies said in a release.

Jacob Van Naarden (Eli Lilly)

Ex­clu­sives: Eli Lil­ly out to crash the megablock­buster PD-(L)1 par­ty with 'dis­rup­tive' pric­ing; re­veals can­cer biotech buy­out

It’s taken 7 years, but Eli Lilly is promising to finally start hammering the small and affluent PD-(L)1 club with a “disruptive” pricing strategy for their checkpoint therapy allied with China’s Innovent.

Lilly in-licensed global rights to sintilimab a year ago, building on the China alliance they have with Innovent. That cost the pharma giant $200 million in cash upfront, which they plan to capitalize on now with a long-awaited plan to bust up the high-price market in lung cancer and other cancers that have created a market worth tens of billions of dollars.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

David Meek, new Mirati CEO (Marlene Awaad/Bloomberg via Getty Images)

Fresh off Fer­Gene's melt­down, David Meek takes over at Mi­rati with lead KRAS drug rac­ing to an ap­proval

In the insular world of biotech, a spectacular failure can sometimes stay on any executive’s record for a long time. But for David Meek, the man at the helm of FerGene’s recent implosion, two questionable exits made way for what could be an excellent rebound.

Meek, most recently FerGene’s CEO and a past head at Ipsen, has become CEO at Mirati Therapeutics, taking the reins from founding CEO Charles Baum, who will step over into the role of president and head of R&D, according to a release.

The biggest ques­tions fac­ing gene ther­a­py, the XLMTM com­mu­ni­ty, and Astel­las af­ter fourth pa­tient death

After three patients died last year in an Astellas gene therapy trial, the company halted the study and began figuring out how to safely get the program back on track. They would, executives eventually explained, cut the dose by more than half and institute a battery of other measures to try to prevent the same thing from happening again.

Then tragically, Astellas announced this week that the first patient to receive the new regimen had died, just weeks after administration.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Ex­elix­is pulls a sur­prise win in thy­roid can­cer just days ahead of fi­nal Cabome­tyx read­out

Exelixis added a thyroid cancer indication to its super-seller Cabometyx’s label on Friday — months before the FDA was expected to make a decision, and days before the company was set to unveil the final data at #ESMO21.

At a median follow-up of 10.1 months, differentiated thyroid cancer patients treated with Cabometyx (cabozantinib) lived a median of 11 months without their disease worsening, compared to just 1.9 months for patients given a placebo, Exelixis said on Monday.

Dave Lennon, former president of Novartis Gene Therapies

Zol­gens­ma patent spat brews be­tween No­var­tis and Re­genxbio as top No­var­tis gene ther­a­py ex­ec de­parts

Regenxbio, a small licensor of gene therapy viral vectors spun out from the University of Pennsylvania, is now finding itself in the middle of some major league patent fights.

In addition to a patent suit with Sarepta Therapeutics from last September, Novartis, is now trying to push its smaller partner out of the way. The Swiss biopharma licensed Regenxbio’s AAV9 vector for its $2.1 million spinal muscular atrophy therapy Zolgensma.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 117,700+ biopharma pros reading Endpoints daily — and it's free.

Ex-My­lan em­ploy­ee pleads guilty to in­sid­er trad­ing, il­le­gal­ly deal­ing on FDA ap­provals, earn­ings and Up­john merg­er

A former Mylan IT executive pleaded guilty Friday to an insider trading scheme where he bought and sold stock options on another executive’s advice.

Prosecutors secured the plea from Dayakar Mallu, Mylan’s former VP of global operations information technology, after uncovering the plan. Mallu collaborated with an unnamed “senior manager,” the SEC said, to trade options ahead of Mylan public announcements regarding FDA approvals, revenue reports and its merger with the Pfizer generics subsidiary Upjohn. The two subsequently shared profits.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 117,700+ biopharma pros reading Endpoints daily — and it's free.

Volker Wagner (L) and Jeff Legos

As Bay­er, No­var­tis stack up their ra­dio­phar­ma­ceu­ti­cal da­ta at #ES­MO21, a key de­bate takes shape

Ten years ago, a small Norwegian biotech by the name of Algeta showed up at ESMO — then the European Multidisciplinary Cancer Conference 2011 — and declared that its Bayer-partnered targeted radionuclide therapy, radium-223 chloride, boosted the overall survival of castration-resistant prostate cancer patients with symptomatic bone metastases.

In a Phase III study dubbed ALSYMPCA, patients who were treated with radium-223 chloride lived a median of 14 months compared to 11.2 months. The FDA would stamp an approval on it based on those data two years later, after Bayer snapped up Algeta and christened the drug Xofigo.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 117,700+ biopharma pros reading Endpoints daily — and it's free.