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.

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.

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.