Roy Baynes, Merck Research Laboratories CMO (file photo)

With at least one gas­tric can­cer ap­proval on the line, Mer­ck­'s Keytru­da scores nod for ear­ly pa­tients in chemo com­bo

Big drug­mak­ers such as Mer­ck and Bris­tol My­ers Squibb are on the fir­ing line with the FDA over ac­cel­er­at­ed on­col­o­gy ap­provals that don’t ace their con­fir­ma­to­ry tri­als. While Keytru­da is in the FDA’s sights for third-line gas­tric can­cer pa­tients, it will add a new ap­proval in com­bi­na­tion with chemo for ear­li­er use.

The FDA ap­proved Mer­ck’s Keytru­da as a com­bi­na­tion ther­a­py with plat­inum- and flu­o­ropy­rim­i­dine-based chemother­a­py to treat first-line pa­tients with metasta­t­ic esophageal can­cer or gas­troe­sophageal junc­tion car­ci­no­ma whose tu­mors can’t be re­moved and aren’t suit­able for ra­di­a­tion, the New Jer­sey phar­ma said Mon­day.

The agency based its re­view on da­ta from the Phase III KEYNOTE-590 tri­al, which found that a com­bi­na­tion of Keytru­da, flu­o­rouracil and cis­platin topped flu­o­rouracil and cis­platin alone in terms of ex­tend­ing pa­tients’ lives.

The Ketyru­da com­bo cut the risk of death by 27% over the chemo con­trol arm and sliced the risk of dis­ease pro­gres­sion or death by 35%. The com­bo post­ed an ORR of 45% com­pared with 29% in the con­trol arm. Those find­ings were con­sis­tent re­gard­less of pa­tients’ tu­mor his­tol­ogy or PD-(L)1 ex­pres­sion.

Esophageal can­cer is the sixth-lead­ing cause of can­cer death in the US with rough­ly 19,000 new cas­es re­port­ed each year, Mer­ck said.

Tak­ing a first-line win in esophageal can­cer and GEJ is a big win giv­en the “few ad­vances in im­prov­ing sur­vival out­comes” in that set­ting over the past few decades, Mer­ck Re­search Lab­o­ra­to­ries’ CMO Roy Baynes said in a state­ment. But the ap­proval will cast an even brighter spot­light on Keytru­da’s ac­cel­er­at­ed nod in gas­tric can­cer and GEJ in third-line or lat­er pa­tients.

In April, the FDA’s On­col­o­gy Cen­ter of Ex­cel­lence will hold a three-day re­view of tar­get­ed ac­cel­er­at­ed ap­provals, in­clud­ing a snap ap­proval grant­ed back in Sep­tem­ber 2017 for Keytru­da in pa­tients who pre­vi­ous­ly re­ceived two rounds of plat­inum- or flu­o­ropy­rim­i­dine-based chemo. That ap­proval was based on re­sults from the KEYNOTE-059 study, part of Mer­ck’s ex­pan­sive gas­tric can­cer pro­gram for Keytru­da to snare a suite of ear­ly- and lat­er-line in­di­ca­tions for the check­point in­hibitor.

The FDA has launched what it’s call­ing an “in­dus­try-wide eval­u­a­tion” of its ac­cel­er­at­ed ap­proval path­way af­ter a se­ries of drug­mak­ers flopped the con­fir­ma­to­ry tri­als for OS and PFS on which the ear­ly de­ci­sions were based. Keytru­da fell vic­tim there in Feb­ru­ary, with Mer­ck pulling its mar­ket­ing ap­proval to treat pa­tients with metasta­t­ic small cell lung can­cer with dis­ease pro­gres­sion on or af­ter plat­inum-based chemother­a­py and at least one oth­er pri­or line of ther­a­py. Both Bris­tol My­ers Squibb with Op­di­vo and As­traZeneca with Imfinzi have faced the FDA’s ire as well.

With that re­view ap­proach­ing, Mer­ck is look­ing to steady the boat for as many Keytru­da de­ci­sions as it can. Last week, the drug­mak­er tout­ed new da­ta show­ing a Keytru­da-Lenvi­ma com­bo nailed its pri­ma­ry pro­gres­sion-free sur­vival and OS end­points in an open-la­bel Phase III study in ad­vanced, metasta­t­ic or re­cur­rent en­dome­tri­al can­cer pa­tients af­ter chemo. The con­fir­ma­to­ry KEYNOTE-775 study broke pa­tients down in­to two main sub­groups based on their mis­match re­pair sta­tus, a key bio­mark­er in de­ter­min­ing whether a spe­cif­ic case of en­dome­tri­al can­cer is hered­i­tary.

Forge Bi­o­log­ics’ cGMP Com­pli­ant and Com­mer­cial­ly Vi­able Be­spoke Affin­i­ty Chro­matog­ra­phy Plat­form

Forge Biologics has developed a bespoke affinity chromatography platform approach that factors in unique vector combinations to streamline development timelines and assist our clients in efficiently entering the clinic. By leveraging our experience with natural and novel serotypes and transgene conformations, we are able to accelerate affinity chromatography development by nearly 3-fold. Many downstream purification models are serotype-dependent, demanding unique and time-consuming development strategies for each AAV gene therapy product1. With the increasing demand to propel AAV gene therapies to market, platform purification methods that support commercial-scale manufacturing of high-quality vectors with excellent safety and efficacy profiles are essential.

Who’s spend­ing and who’s cut­ting from Big Phar­ma’s $127B R&D bud­get? Here are the top 15 play­ers

A couple of the Big 15 biopharma companies in R&D hit the gas on research spending last year. Merck and Sanofi still have lots to prove in the pipeline, and they’re willing to gamble large sums to make a better future for themselves.

Doing nothing would be infinitely worse.

But collectively, the top players rang up a modest 2.4% increase in spending in 2022, which didn’t cover inflationary pressures. And that set the tone for an extraordinarily cautious year for the industry — even as it laid out about $127 billion to advance new drugs or up the ante on approved therapies.

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Jeff Bluestone (R), Sonoma Biotherapeutics CEO

Jef­frey Blue­stone brings his start­up haul to $400M+, join­ing forces with Re­gen­eron on cell ther­a­pies

These days, when Jeffrey Bluestone gets together with his contemporaries in science, the conversation often turns to retirement plans.

But a little more than three years ago, Bluestone reached a momentous turning point in his career, exiting a prestigious post at UCSF, where he had spent decades in the scientific pursuit of new therapies. And it had nothing to do with retirement anytime in the near future.

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Sally Susman, Pfizer EVP and chief corporate affairs officer

Q&A: Pfiz­er cor­po­rate com­mu­ni­ca­tions chief Sal­ly Sus­man dis­cuss­es book craft­ed in pan­dem­ic and per­son­al lessons

From the political arena to the finance and beauty industries to pharmaceuticals, Pfizer’s Sally Susman has broken barriers, stereotypes and conventions. And now the chief communicator is “Breaking Through,” the title of her first book about effective and innovative communications launching today. The full official title is “Breaking Through: Communicating to Open Minds, Move Hearts, and Change the World.”

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Gun­ning for 2023 ap­proval, GSK de­tails PhI­II da­ta for Jem­per­li in front­line en­dome­tri­al can­cer

GSK has a new slate of data to offer on its PD-1 inhibitor, Jemperli — data that the pharma giant hopes will cement one of the four drug approvals it’s expecting this year.

While Jemperli (dostarlimab) is already approved for a subset of patients with second-line endometrial cancer, GSK set out in the Phase III RUBY trial to test it as an earlier line of treatment while also enrolling a broader group of patients. In an interim analysis, Jemperli was shown to extend progression-free survival for both the subset and the overall trial population when added to chemotherapy.

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Es­pe­ri­on sues Dai­ichi Sankyo, de­mand­ing pay­ment of $300M mile­stone for car­dio drug

Esperion is suing its business partner Daiichi Sankyo, saying the Japanese drugmaker is improperly refusing to pay a $300 million milestone that the biotech company will be owed after reporting positive data from a large trial of its cardiovascular drug Nexletol.

The 2019 deal between the companies had Daiichi Sankyo pay $150 million upfront plus another $150 million after the first sales of the drug. But another major payout was tied to an outcomes study reported this month, known as CLEAR. Esperion, in its suit against Daiichi, argues that the drug’s more than 20% reduction of heart attack risk is enough to trigger a $300 million payout from Daiichi once it’s added to the drug’s label.

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Robert Califf, FDA commissioner (Photo by Drew Angerer/Getty Images)

House com­mit­tee to in­ves­ti­gate FDA's re­sponse to on­go­ing drug short­ages

Republican leaders of the House Committee on Energy & Commerce sent a five-page letter yesterday announcing an investigation into the ongoing drug shortages that have rankled the US during the pandemic and the FDA’s response to it.

The letter, signed by Chair Cathy McMorris Rodgers (R-WA), explains how shortages have become more common over the past decade, while pointing to a report from the National Academies of Science, Engineering and Medicine finding that drug shortages have been “on the rise” over the past several decades and are lasting longer, with new drug shortages in the US seeing a 30% increase from 2021 to 2022.

Eli Lil­ly to in­crease in­vest­ment to $1B in­to new Irish man­u­fac­tur­ing fa­cil­i­ty — re­port

The US pharma giant Eli Lilly will be increasing its financial commitment to a manufacturing site in Ireland.

According to a release from Ireland’s Industrial Development Agency (IDA) on Monday, Lilly will be investing another $500 million in its manufacturing facility in Limerick, Ireland — bringing the total investment into the facility to approximately $1 billion.

In January of last year, Lilly announced it was placing a $446 million investment into the site to expand active pharmaceutical ingredient and monoclonal antibody production.

Uğur Şahin, BioNTech CEO (Andreas Arnold/picture-alliance/dpa/AP Images)

BioN­Tech read­ies for plunge in Covid sales, will boost mR­NA and on­col­o­gy pipelines

BioNTech is estimating €5 billion (nearly $5.4 billion) in Covid-19 vaccine sales this year, a marked drop from €17.1 billion ($18.5 billion) in 2022 — and way off analysts’ expectations of around €8 billion ($8.6 billion).

In BioNTech’s year-end earnings call on Monday, it reported a total of €17.3 billion ($18.7 billion) in 2022 revenue, almost all from vaccine sales, which include those via its Pfizer deal and direct sales.

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