#AS­CO21: Mer­ck tacks on ar­mor in ear­ly-line can­cer fight with 2 Keytru­da wins set­ting the tone

With more and more PD-(L)1 check­point in­hibitors flood­ing the mar­ket, there has been a long-run­ning war over which of those drugs can se­cure a lead in ear­ly-line pa­tients. With Keytru­da on top of the world, Mer­ck is well-po­si­tioned to take the lead — and it’s rolling out a pair of stud­ies tar­get­ed di­rect­ly at that front.

As part of a broad plan of at­tack to bring I-O won­der drug Keytru­da in­to ear­li­er lines of metasta­t­ic can­cer, Mer­ck will un­veil win­ning re­sults at this year’s AS­CO from Phase II and Phase III tests as part of com­bi­na­tion ther­a­pies top­ping stan­dard of care in non-small cell lung and gas­tric can­cers.

First, a com­bi­na­tion ther­a­py of Keytru­da and stan­dard-of-care Her­ceptin plus chemother­a­py post­ed a con­firmed over­all re­sponse rate of 74% com­pared with 52% for place­bo+SOC in first-line pa­tients with HER2-pos­i­tive gas­tric or gas­troe­sophageal can­cer, ac­cord­ing to da­ta from the Phase III KEYNOTE-811 study.

It’s the first con­fer­ence pre­sen­ta­tion for KEYNOTE-811, worth point­ing out as the FDA al­ready grant­ed the com­bi­na­tion an ac­cel­er­at­ed ap­proval ear­li­er this month. The com­plete re­sponse rate for the com­bo was 11.3% com­pared with 3.1% with a me­di­an du­ra­tion of re­sponse of 10.3 months com­pared with 9.6 months, re­spec­tive­ly. Mean­while, the com­bo’s safe­ty re­sults were com­pa­ra­ble with stan­dard of care with no new safe­ty flags.

Roy Baynes

The da­ta are a bit af­ter the fact with the ap­proval in hand, but Mer­ck Re­search Labs CMO Roy Baynes told End­points News the re­sults are part of an es­ca­lat­ing bat­tle among drug­mak­ers to bring I-O med­i­cines in­to ear­li­er and ear­li­er lines of ther­a­py. For Mer­ck, that strat­e­gy hinges around the use of com­bi­na­tion ther­a­pies for Keytru­da, which have shown a lot more promise than sub­sti­tut­ing monother­a­py for es­tab­lished stan­dard of care in terms of tu­mor re­sponse.

“What you’re see­ing is of­ten­times in the com­bi­na­to­r­i­al set­ting, the bio­mark­er be­comes less im­por­tant, re­sponse rates are of­ten­times quite a lot high­er, and we’re of­ten able to ad­dress pop­u­la­tions that gen­er­al­ly were not nec­es­sar­i­ly ben­e­fit­ing max­i­mal­ly from monother­a­py,” he said.

At AS­CO, Mer­ck will al­so present da­ta from KEYNOTE-799, a Phase II study of Keytru­da plus plat­inum-based chemother­a­py and ra­dio­ther­a­py in first-line, lo­cal­ly ad­vanced stage III non-small cell lung can­cer pa­tients whose tu­mors can’t be sur­gi­cal­ly re­moved.

The cur­rent stan­dard of care in that set­ting is chemora­di­a­tion fol­lowed by a “con­sol­i­da­tion reg­i­men” of As­traZeneca’s Imfinzi. Up to 30% of those pa­tients can­not com­plete the Imfinzi reg­i­men, of­fer­ing a big un­met clin­i­cal need.

Ac­cord­ing to ear­ly re­sults, the Keytru­da com­bo post­ed a over­all re­sponse rate around 70% across two co­horts of pa­tients with ei­ther squa­mous or non-squa­mous NSCLC re­ceiv­ing two sep­a­rate chemora­di­a­tion reg­i­men plus Keytru­da or Keytru­da alone. The com­bined com­plete and par­tial re­spons­es in Co­hort A were 79 and 72 in Co­hort B. The du­ra­tion of re­sponse rate af­ter 12 months was 80% and 76%, re­spec­tive­ly.

Most im­por­tant­ly on the safe­ty front, the com­bi­na­tion of chemora­di­a­tion and Keytru­da didn’t spur a high rate of pneu­moni­tis — or lung in­flam­ma­tion — in the pa­tient pop­u­la­tion, Baynes said. Both ther­a­pies tak­en alone have been tied to pneu­moni­tis, and in­ves­ti­ga­tors close­ly mon­i­tored pa­tients to see how that safe­ty flag would progress.

With proof-of-con­cept se­cured, Mer­ck is al­so chas­ing a Phase III study for Keytru­da on top of chemora­di­a­tion fol­lowed by ei­ther Keytru­da alone or in com­bi­na­tion with PARP in­hibitor Lyn­parza as part of the KEY­LYNK-012 study.

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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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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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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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