#AACR: Bris­tol-My­ers tunes out sta­t­ic, broad­casts im­pres­sive re­sults for Op­di­vo/Yer­voy lung can­cer com­bo

CHICA­GO — Bris­tol-My­ers Squibb $BMY ran smack dab in­to a high lev­el of pro­fes­sion­al sta­t­ic when it changed up its study de­sign for Check­mate-227, a piv­otal test for Op­di­vo plus Yer­voy in treat­ing new cas­es of non-small cell lung can­cer. But they’ve ar­rived at AACR with da­ta they say spell out a com­pelling case for their PD-1/CT­LA-4 com­bo.

Fouad Namouni

“The da­ta we re­port here are ex­cit­ing,” says Fouad Namouni, the on­col­o­gy de­vel­op­ment chief at Bris­tol-My­ers, “with an im­por­tant lev­el of ac­tiv­i­ty.”

Their drug re­duced the risk of pro­gres­sion or death by 42% with a haz­ard ra­tio of 0.58.

At the one-year mark, Namouni told me in a pre­view of to­day’s re­lease, the pro­gres­sion-free sur­vival rate in the com­bo arm was 43%, com­pared to on­ly 13% in the con­trol arm. And that’s re­gard­less of PD-L1 ex­pres­sion sta­tus and his­tol­ogy, with no changes for squa­mous or non­squa­mous cas­es.

Re­searchers in­volved in the study ripped up the orig­i­nal tri­al de­sign, mesh­ing da­ta to­geth­er and claim­ing a suc­cess against a nov­el goal for pa­tients with a “high tu­mor mu­ta­tion bur­den.” And they went their own way on defin­ing the TMB so that it in­clud­ed close to half of all pa­tients in the pop­u­la­tion, rather than the more min­i­mal sub­group tracked by the test mak­er Foun­da­tion Med­i­cine, which us­es a bar that is set twice as high to clas­si­fy pa­tients.

Clear­ly, Namouni says, this marks a big ad­vance for pa­tients — to say noth­ing about their in­tense ri­val­ry with Mer­ck. And he adds that it makes sense.

“A high tu­mor mu­ta­tion bur­den is a sur­ro­gate for neo-anti­gens,” he adds, which makes the tu­mor more vis­i­ble to the im­mune sys­tem, and in turn makes it more like­ly to be re­spon­sive to a PD-1/L1 check­point.

Their work here, says Namouni, in­volves deep­en­ing the field’s un­der­stand­ing of the bi­ol­o­gy of lung can­cer. 

They’ve al­so got ev­i­dence to back up their po­si­tion that 10 mu­ta­tions/megabase is the right in­flec­tion point, rather than mov­ing the scale up even as high as 15. The Foun­da­tion test sets the mark at 20.

For some ri­vals, that kind of as­ser­tion looks like a boast that can’t be proven at this ear­ly stage of the game. But in a chat with As­traZeneca’s David Berman, their chief of I/O pro­grams, he agreed that their own work backed up the stan­dard used by Bris­tol-My­ers — not­ing that in lung can­cer specif­i­cal­ly 10 mu­ta­tions/megabase marked the right cut­off for the as­say on high TMB. Every can­cer type is dif­fer­ent, he adds, and they’ve been care­ful­ly study­ing this them­selves in their work on dur­val­um­ab in lung can­cer.

There are oth­er prob­lems that are pre­sent­ed by us­ing the test, though. One is that it cur­rent­ly takes about 2 weeks to get back re­sults on the tu­mor mu­ta­tion bur­den, and some crit­ics say pa­tients and doc­tors may not want to de­lay ther­a­py to run the test. But Bris­tol-My­ers’ Namouni says that that is with­in the usu­al con­sul­ta­tion time it takes to de­cide on ther­a­py — adding that what takes 2 weeks now could be quick­ly sliced back to a cou­ple of days with the prop­er fo­cus.

Bris­tol-My­ers’ ap­proach may con­tin­ue to raise hack­les among some ob­servers — but this is a high­ly re­spect­ed R&D or­ga­ni­za­tion that is de­ter­mined to re­main a leader in lung can­cer, come what may or might at Mer­ck or any of its oth­er ri­vals.

Namouni says they’ve been in con­ver­sa­tions with reg­u­la­to­ry groups about the da­ta, but he isn’t of­fer­ing any time­lines on fil­ings. 

ZS Per­spec­tive: 3 Pre­dic­tions on the Fu­ture of Cell & Gene Ther­a­pies

The field of cell and gene therapies (C&GTs) has seen a renaissance, with first generation commercial therapies such as Kymriah, Yescarta, and Luxturna laying the groundwork for an incoming wave of potentially transformative C&GTs that aim to address diverse disease areas. With this renaissance comes several potential opportunities, of which we discuss three predictions below.

Allogenic Natural Killer (NK) Cells have the potential to displace current Cell Therapies in oncology if proven durable.

Despite being early in development, Allogenic NKs are proving to be an attractive new treatment paradigm in oncology. The question of durability of response with allogenic therapies is still an unknown. Fate Therapeutics’ recent phase 1 data for FT516 showed relatively quicker relapses vs already approved autologous CAR-Ts. However, other manufacturers, like Allogene for their allogenic CAR-T therapy ALLO-501A, are exploring novel lymphodepletion approaches to improve persistence of allogenic cells. Nevertheless, allogenic NKs demonstrate a strong value proposition relative to their T cell counterparts due to comparable response rates (so far) combined with the added advantage of a significantly safer AE profile. Specifically, little to no risk of graft versus host disease (GvHD), cytotoxic release syndrome (CRS), and neurotoxicity (NT) have been seen so far with allogenic NK cells (Fig. 1). In addition, being able to harness an allogenic cell source gives way to operational advantages as “off-the-shelf” products provide improved turnaround time (TAT), scalability, and potentially reduced cost. NKs are currently in development for a variety of overlapping hematological indications with chimeric antigen receptor T cells (CAR-Ts) today, and the question remains to what extent they will disrupt the current cell therapy landscape. Click for more details.

Susan Galbraith, AstraZeneca EVP, Oncology R&D

Can­cer pow­er­house As­traZeneca rolls the dice on a $75M cash bet on a buzzy up­start in the on­col­o­gy field

After establishing itself in the front ranks of cancer drug developers and marketers, AstraZeneca is putting its scientific shoulder — and a significant amount of cash — behind the wheel of a brash new upstart in the biotech world.

The pharma giant trumpeted news this morning that it is handing over $75 million upfront to ally itself with Scorpion Therapeutics, one of those biotechs that was newly birthed by some top scientific, venture and executive talent and bequeathed with a fortune by way of a bankroll to advance an only hazily explained drug platform. And they are still very much in the discovery and preclinical phase.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 128,900+ biopharma pros reading Endpoints daily — and it's free.

Lat­est news on Pfiz­er's $3B+ JAK1 win; Pacts over M&A at #JPM22; 2021 by the num­bers; Bio­gen's Aduhelm reck­on­ing; The sto­ry of sotro­vimab; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

For those of you who attended #JPM22 in any shape or form, we hope you had a fruitful time. Regardless of how you spent the past hectic week, may your weekend be just what you need it to be.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 128,900+ biopharma pros reading Endpoints daily — and it's free.

A $3B+ peak sales win? Pfiz­er thinks so, as FDA of­fers a tardy green light to its JAK1 drug abroc­i­tinib

Back in the fall of 2020, newly crowned Pfizer chief Albert Bourla confidently put their JAK1 inhibitor abrocitinib at the top of the list of blockbuster drugs in the late-stage pipeline with a $3 billion-plus peak sales estimate.

Since then it’s been subjected to serious criticism for the safety warnings associated with the class, held back by a cautious FDA and questioned when researchers rolled out a top-line boast that their heavyweight contender had beaten the champ in the field of atopic dermatitis — Dupixent — in a head-to-head study.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 128,900+ biopharma pros reading Endpoints daily — and it's free.

Robert Califf, FDA commissioner nominee (Graeme Sloan/Sipa USA/Sipa via AP Images)

Rob Califf ad­vances as Biden's FDA nom­i­nee, with a close com­mit­tee vote

Rob Califf’s second confirmation process as FDA commissioner is already much more difficult than his near unanimous confirmation under the Obama administration.

The Senate Health Committee on Thursday voted 13-8 in favor of advancing Califf’s nomination to a full Senate vote. Several Democrats voted against Califf, including Sen. Bernie Sanders and Sen. Maggie Hassan. Several other Democrats who aren’t on the committee, like West Virginia’s Joe Manchin and Ed Markey of Massachusetts, also said Thursday that they would not vote for Califf. Markey, Hassan and Manchin all previously expressed reservations about the prospect of Janet Woodcock as an FDA commissioner nominee too.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 128,900+ biopharma pros reading Endpoints daily — and it's free.

Michel Vounatsos, Biogen CEO (World Economic Forum/Ciaran McCrickard)

Bio­gen vows to fight CM­S' draft cov­er­age de­ci­sion for Aduhelm be­fore April fi­nal­iza­tion

Biogen executives made clear in an investor call Thursday they are not preparing to run a new CMS-approved clinical trial for their controversial Alzheimer’s drug anytime soon.

As requested in a draft national coverage decision from CMS earlier this week, Biogen and other anti-amyloid drugs will need to show “a meaningful improvement in health outcomes” for Alzheimer’s patients in a randomized, placebo-controlled trial to get paid for their drugs, rather than just the reduction in amyloid plaques that won Aduhelm its accelerated approval in June.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 128,900+ biopharma pros reading Endpoints daily — and it's free.

CRO own­er pleads guilty to ob­struct­ing FDA in­ves­ti­ga­tion in­to fal­si­fied clin­i­cal tri­al da­ta

The co-owner of a Florida-based clinical research site pleaded guilty to lying to an FDA investigator during a 2017 inspection, revealing that she falsely portrayed part of a GlaxoSmithKline pediatric asthma study as legitimate, when in fact she knew that certain data had been falsified, the Department of Justice said Wednesday.

Three other employees — Yvelice Villaman Bencosme, Lisett Raventos and Maytee Lledo — previously pleaded guilty and were sentenced in connection with falsifying data associated with the trial at the CRO Unlimited Medical Research.

‘Skin­ny la­bels’ on gener­ics can save pa­tients mon­ey, re­search shows, but re­cent court de­ci­sions cloud fu­ture

New research shows how generic drug companies can successfully market a limited number of approved indications for a brand name drug, prior to coming to market for all of the indications. But several recent court decisions have created a layer of uncertainty around these so-called “skinny” labels.

While courts have generally allowed generic manufacturers to use their statutorily permitted skinny-label approvals, last summer, a federal circuit court found that Teva Pharmaceuticals was liable for inducing prescribers and patients to infringe GlaxoSmithKline’s patents through advertising and marketing practices that suggested Teva’s generic, with its skinny label, could be employed for the patented uses.

A patient in Alaska receiving an antibody infusion to prevent Covid hospitalizations in September. All but one of these treatments has been rendered useless by Omicron (Rick Bowmer/AP Images)

How a tiny Swiss lab and two old blood sam­ples cre­at­ed one of the on­ly ef­fec­tive drugs against Omi­cron (and why we have so lit­tle of it)

Exactly a decade before a novel coronavirus broke out in Wuhan, Davide Corti — a newly-minted immunologist with frameless glasses and a quick laugh — walked into a cramped lab on the top floor of an office building two hours outside Zurich. He had only enough money for two technicians and the ceiling was so low in parts that short stature was a job requirement, but Corti believed it’d be enough to test an idea he thought could change medicine.

Endpoints Premium

Premium subscription required

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