Keytru­da’s ac­cel­er­at­ed ap­proval in a com­mon form of liv­er can­cer looked shaky af­ter the drug failed on two sur­vival mea­sures in a con­fir­ma­to­ry study al­most three years ago. Now Mer­ck’s tout­ing what could be a con­fir­ma­to­ry win — but will three pa­tient deaths mar its chances?

A reg­i­men of Keytru­da plus best sup­port­ive care re­duced pa­tients’ risk of death by 21% com­pared to place­bo plus sup­port­ive care (p=0.0180), meet­ing the pri­ma­ry end­point in the Phase III KEYNOTE-394 study, Mer­ck an­nounced on Tues­day. The tri­al en­rolled 453 Asian pa­tients with ad­vanced he­pa­to­cel­lu­lar car­ci­no­ma (HCC), who had pre­vi­ous­ly been treat­ed with so­rafenib or ox­ali­platin-based chemother­a­py.

Pa­tients in the Keytru­da arm saw an over­all sur­vival of 14.6 months com­pared to 13 months in the place­bo arm, and 34.3% of Keytru­da pa­tients were still alive at the two-year mark com­pared to 24.9% of place­bo pa­tients.

How­ev­er, there were three deaths in the Keytru­da arm “re­lat­ed to the study in­ter­ven­tion,” Mer­ck said, caused by gas­troin­testi­nal he­m­or­rhage, au­toim­mune he­pati­tis and soft tis­sue in­fec­tion. Pa­tients in the Keytru­da arm al­so saw high­er rates of treat­ment-emer­gent side ef­fects, in­clud­ing im­mune-me­di­at­ed ad­verse events, ac­cord­ing to Mer­ck.

That could give Op­di­vo and Yer­voy a leg up in this set­ting, where the drug com­bo post­ed one treat­ment-re­lat­ed death in the open-la­bel Check­Mate-040 tri­al (due to pneu­moni­tis). How­ev­er, Bris­tol My­ers Squibb vol­un­tar­i­ly pulled Op­di­vo from the mar­ket as a so­lo ther­a­py for HCC back in Ju­ly, as the FDA’s On­co­log­ic Drugs Ad­vi­so­ry Com­mit­tee held an in­dus­try-wide eval­u­a­tion of ac­cel­er­at­ed ap­provals for check­point in­hibitors that have not met their post-mar­ket­ing re­quire­ments to show con­fir­ma­to­ry ben­e­fit.

Keytru­da won ac­cel­er­at­ed ap­proval in HCC back in 2018 based on some ear­li­er mid-stage da­ta. But when the drug failed the KEYNOTE-240 study a few months lat­er, its fu­ture looked murky. That tri­al missed the mark on both over­all sur­vival as well as pro­gres­sion-free sur­vival.

ODAC vot­ed unan­i­mous­ly for keep­ing Keytru­da on the mar­ket last April, as the ad­comm con­tin­ued its re­view of so-called “dan­gling ap­provals.” Mer­ck had as­sert­ed the Keytru­da reg­i­men was still nec­es­sary for sec­ond-line pa­tients de­spite a re­cent ap­proval for a Tecen­triq-Avastin com­bo in first-line HCC. Richard Finn, a pro­fes­sor of med­i­cine at UCLA and paid con­sul­tant for Mer­ck, said at the time that pulling the HCC ap­proval didn’t make sense giv­en more da­ta were com­ing in just a few months.

Mer­ck says it’s dis­cussing the KEYNOTE-394 da­ta with reg­u­la­tors around the world, and the tri­al will be eval­u­at­ed as a po­ten­tial con­fir­ma­to­ry study in the US.

Scot Ebbing­haus

“Pa­tients with ad­vanced HCC still have a high un­met med­ical need with low sur­vival rates, re­in­forc­ing the need for treat­ment op­tions that can im­prove over­all sur­vival,” Scot Ebbing­haus, VP of clin­i­cal re­search at Mer­ck Re­search Lab­o­ra­to­ries, said in a state­ment on Tues­day. “We are pleased to share these new da­ta from KEYNOTE-394 and are com­mit­ted to ad­vanc­ing re­search for pa­tients with this dif­fi­cult-to-treat can­cer through our broad glob­al pro­gram in HCC.”

Mer­ck didn’t get so lucky with all of its Keytru­da in­di­ca­tions, as ODAC rec­om­mend­ed against keep­ing Keytru­da’s ac­cel­er­at­ed OK in third-line stom­ach can­cer. The phar­ma gi­ant sub­se­quent­ly pulled the drug in Ju­ly.

Cor­rec­tion: Pa­tients in KEYNOTE-394 re­ceived Keytru­da along with best sup­port­ive care, not best stan­dard-of-care.

The story of Amryt Pharma’s candidate for the genetic skin condition epidermolysis bullosa, or EB, will soon enter another chapter.

After the Irish drugmaker’s candidate, dubbed Oleogel-S10 and marketed as Filsuvez, was handed a CRL earlier this year, the company announced in a press release that it plans to submit a formal dispute resolution request for the company’s NDA for Oleogel-S10.

North Carolina Republican Sen. Thom Tillis made a name for himself in the 2020 election cycle as the darling of the pharma industry, accepting hundreds of thousands in campaign contributions, even from the likes of Pfizer CEO Albert Bourla.

Those contributions have led Tillis to attempt to re-write patent laws in pharma’s favor, a move which failed to gain steam in 2019, and request for a third time since January that the FDA should help stop “the false narrative that patent protections are to blame for high drug prices.”