#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. 

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Gold for adults, sil­ver for in­fants: Pfiz­er's Pre­vnar 2.0 head­ed to FDA months af­ter Mer­ck­'s green light

Pfizer was first to the finish line for the next-gen pneumococcal vaccine in adults, but Merck beat its rival with a jab for children in June.

Now, two months after Merck’s 15-valent Vaxneuvance won the FDA stamp of approval for kids, Pfizer is out with some late-stage data on its 20-valent shot for infants.

Known as Prevnar 20 for adults, Pfizer’s 20vPnC will head to the FDA by the end of this year for an approval request in infants, the Big Pharma said Friday morning. Discussions with the FDA will occur first and more late-stage pediatric trials are expected to read out soon, informing the regulatory pathway in other countries and regions.

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His­toric drug pric­ing re­forms pass; Pfiz­er ac­quires GBT; The long search for non-opi­oid pain drugs; 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.

The Endpoints Weekly has officially crossed the 60,000 mark on subscribers — thanks to all of your support. As the editorial team grows, we’ve been able to do a lot more, with many of those on display this week. Be sure to check out Lei Lei Wu’s deep dive on pain R&D. If you missed it, you may also rewatch her companion panel here.

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No­var­tis re­ports two pa­tient deaths af­ter treat­ment with Zol­gens­ma

Two children with spinal muscular atrophy have died after receiving Novartis’ Zolgensma, a gene therapy designed as a one-time treatment for the rare fatal disease.

The deaths, which resulted from acute liver failure, occurred in Russia and Kazakhstan, Novartis confirmed in a statement to Endpoints News. Having notified health authorities across all the markets where Zolgensma is available, it will update the drug label “to specify that fatal acute liver failure has been reported,” a spokesperson wrote.

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House pass­es his­toric drug pric­ing re­forms, lin­ing up decades-in-the-mak­ing win for Biden and De­moc­rats

The US House of Representatives today voted along party lines (all Dems voted for it), 220-207 to pass new, wide-ranging legislation that will allow Medicare drug price negotiations for the first time ever, and cap seniors’ drug expenses to $2,000 per year and seniors’ insulin costs at $35 per month.

Setting up a major victory for President Joe Biden, representatives returned from their summer recess to pass the Inflation Reduction Act, even as many noted the bill would only modestly reduce inflation.

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Senate Finance Committee Chair Ron Wyden (D-OR) (Francis Chung/E&E News/POLITICO via AP Images)

Sen­ate Fi­nance chair con­tin­ues his in­ves­ti­ga­tion in­to phar­ma tax­es with re­quests for Am­gen

Amgen is the latest pharma company to appear on the radar of Senate Finance Committee Chair Ron Wyden (D-OR), who is investigating the way pharma companies are using subsidiaries in low- or zero-tax countries to lower their tax bills.

Like its peers Merck, AbbVie and Bristol Myers Squibb, Wyden notes how Amgen uses its Puerto Rico operations to consistently pay tax rates that are substantially lower than the U.S. corporate tax rate of 21%, with an effective tax rate of 10.7% in 2020 and 12.1% in 2021.

FDA ap­proves sec­ond in­di­ca­tion for As­traZeneca and Dai­ichi's En­her­tu in less than a week

AstraZeneca and Daiichi Sankyo’s antibody-drug conjugate Enhertu scored its second approval in less than a week, this time for a subset of lung cancer patients.

Enhertu received accelerated approval on Thursday to treat adults with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations, and who have already received a prior systemic therapy.

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J&J to re­move talc prod­ucts from shelves world­wide, re­plac­ing with corn­starch-based port­fo­lio

After controversially spinning out its talc liabilities and filing for bankruptcy in an attempt to settle 38,000 lawsuits, Johnson & Johnson is now changing up the formula for its baby powder products.

J&J is beginning the transition to an all cornstarch-based baby powder portfolio, the pharma giant announced on Thursday — just months after a federal judge ruled in favor of its “Texas two-step” bankruptcy to settle allegations that its talc products contained asbestos and caused cancer. An appeals court has since agreed to revisit that case.

CSL is gathering its four business units under a unified brand identity strategy (Credit: CSL company site)

CSL brings Se­qirus, Vi­for un­der par­ent um­brel­la brand in iden­ti­ty re­vamp

CSL is gathering its brands under the family name umbrella, renaming its vaccine and newly acquired nephrology specialty businesses with the parent initials.

CSL Seqirus and CSL Vifor join CSL Plasma and CSL Behring as the four now uniformly branded business units of the global biopharma. The Seqirus vaccine division was formed in 2015 with the combination of bioCSL and its purchase of Novartis’ flu vaccine business. CSL picked up Vifor Pharma late last year in an $11.7 billion deal for the nephrology, iron deficiency and cardio-renal drug developer.

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