Robert Davis, Merck CEO

Al­most three years af­ter whiff­ing in a con­fir­ma­to­ry study, Mer­ck touts new da­ta for Keytru­da in HCC

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.

M&A: a crit­i­cal dri­ver for sus­tain­able top-line growth in health­care

2021 saw a record $600B in healthcare M&A activity. In 2022, there is an anticipated slowdown in activity, however, M&A prospects remain strong in the medium to long-term. What are future growth drivers for the healthcare sector? Where might we see innovations that drive M&A? RBC’s Andrew Callaway, Global Head, Healthcare Investment Banking discusses with Vito Sperduto, Global Co-Head, M&A.

15 LGBTQ lead­ers in bio­phar­ma; Paul Stof­fels’ Gala­pa­gos re­vamp; As­traZeneca catch­es up in AT­TR; 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.

A return to in-person conferences also marks a return to on-the-ground reporting. My colleagues Beth Synder Bulik and Nicole DeFeudis were on-site at Cannes Lions, bringing live coverage of pharma’s presence at the ad festival — accompanied by photos from Clara Bui, our virtual producer, that bring you right to the scene. You can find a recap (and links to all the stories) below.

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David Loew (Ipsen)

Ipsen snags an ap­proved can­cer drug in $247M M&A deal as an­oth­er bat­tered biotech sells cheap

You can add Paris-based Ipsen to the list of discount buyers patrolling the penny stock pack for a cheap M&A deal.

The French biotech, which has had plenty of its own problems to grapple with, has swooped in to buy Epizyme $EPZM for $247 million in cash and a CVR with milestones attached to it. Epizyme shareholders, who had to suffer through a painfully soft launch of their EZH2a inhibitor cancer drug Tazverik, will get $1.45 per share along with a $1 CVR tied to achieving $250 million in sales from the drug over four consecutive quarters as well as an OK for second-line follicular lymphoma by 1 Jan. 2028.

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AstraZeneca's new Evusheld direct to consumer campaign aims to reach more immunocompromised patients.

As­traZeneca de­buts first con­sumer cam­paign for its Covid-19 pro­phy­lac­tic Evusheld — and a first for EUA drugs

AstraZeneca’s first consumer ad for Evusheld is also a first for drugs that have been granted emergency use authorizations during the pandemic.

The first DTC ad for a medicine under emergency approval, the Evusheld campaign launching this week aims to raise awareness among immunocompromised patients — and spur more use.

Evusheld nabbed emergency authorization in December, however, despite millions of immunocompromised people looking for a solution and now more widespread availability of the drug.

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Joe Wiley, Amryt Pharma CEO

Am­ryt Phar­ma sub­mits a for­mal dis­pute res­o­lu­tion to the FDA over re­ject­ed skin dis­ease drug

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.

Sen. Thom Tillis (R-NC) (J. Scott Applewhite/AP Images)

Phar­ma-friend­ly sen­a­tor calls on FDA for a third time to show patent pro­tec­tions should­n't be blamed for high drug prices

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.”

EMA signs off on 3 drugs re­cent­ly re­ject­ed by FDA, in­clud­ing Bio­Mar­in's new he­mo­phil­ia gene ther­a­py

The EMA’s human medicines committee on Friday recommended three new drugs for approval or conditional approval, even as their US counterparts have rejected these three for various reasons.

In a major move, CHMP offered a thumbs-up to a conditional marketing authorization for the first gene therapy to treat severe hemophilia A, although the agency cautioned that it’s so far unknown how long the effects of infusion will last.

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Alarmed by side ef­fect, FDA slaps clin­i­cal hold on Sarep­ta's next-gen Duchenne drug

Sarepta Therapeutics’ next-gen Duchenne muscular dystrophy drug has been hit with a clinical hold after investigators flagged a serious case of low magnesium levels in one patient’s blood.

Screening and dosing will be halted in what is known as Part B of the Phase II MOMENTUM study, which has enrolled about half of the planned patients. Sarepta said it will be submitting information on all cases of the condition, known as hypomagnesemia, per the FDA’s request and proposing some changes to the risk mitigation and safety monitoring plan.

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When will the FDA re­scind a break­through des­ig­na­tion? New draft guid­ance spells out the com­pli­cat­ed de­tails

Although it’s exceedingly rare for the FDA to rescind a breakthrough designation once it’s granted, there has been a recent uptick — as in 2020 and 2021 combined, the agency rescinded 17 BTDs, compared to just 18 rescinded from 2015 to 2019 combined.

Protagonist Therapeutics saw this reality up close and personal in April after a clinical hold lifted on its experimental blood cancer drug, as the company revealed that the FDA sought to revoke the BTD. The decision, Protagonist says, stems from “observed malignancies” related to the hold, initially imposed in September 2021.

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