Weeks af­ter Keytru­da CRL in high-risk TNBC, Mer­ck claims a win af­ter da­ta ma­ture. How soon will it re­turn to FDA?

There’s been much afoot re­gard­ing Mer­ck’s at­tempts to ex­pand its block­buster Keytru­da drug in­to high-risk, ear­ly-stage triple-neg­a­tive breast can­cer so far in 2021.

In ear­ly Feb­ru­ary, well af­ter Mer­ck had sub­mit­ted its sup­ple­men­tal BLA for the in­di­ca­tion, the FDA’s ODAC unan­i­mous­ly re­buked the phar­ma’s pitch, say­ing the da­ta were too im­ma­ture to be con­clu­sive. FDA can­cer czar Richard Paz­dur took the ex­tra­or­di­nary step of ad­mon­ish­ing Mer­ck dur­ing the meet­ing, say­ing the com­pa­ny should not have as­sumed or hoped for a pos­i­tive re­sult be­fore the piv­otal study read out. A few weeks lat­er, reg­u­la­tors un­sur­pris­ing­ly hand­ed Mer­ck a com­plete re­sponse let­ter.

Now, though, the study has reached the in­ter­im analy­sis check­point. And Mer­ck says it’s a win­ner.

The KEYNOTE-522 study — the same tri­al un­der the mi­cro­scope in Feb­ru­ary’s ad­comm — met its dual pri­ma­ry end­point of event-free sur­vival, Mer­ck an­nounced Thurs­day morn­ing, demon­strat­ing a sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment in EFS com­pared to the con­trol. Its oth­er pri­ma­ry end­point, patho­log­i­cal com­plete re­sponse, had pre­vi­ous­ly been met.

Roy Baynes

“Now that we are see­ing the da­ta ma­ture af­ter four years to in­clude a sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment in event-free sur­vival, we look for­ward to work­ing with the FDA and oth­er glob­al au­thor­i­ties,” Roy Baynes, CMO of Mer­ck Re­search Lab­o­ra­to­ries, said in a state­ment.

Mer­ck has been look­ing to ex­pand Keytru­da in­to this TNBC pop­u­la­tion as both a pre-op­er­a­tive (with chemo) and post-op (with­out chemo) treat­ment. The ear­ly da­ta pre­sent­ed at Feb­ru­ary’s ad­comm proved a re­al stick­ing point, with even some pa­tient ad­vo­cates won­der­ing what the rush was all about.

At the time of the last check-in, re­searchers had seen just 53% of tar­get­ed EFS events and 32% of over­all sur­vival events.

It’s not yet clear whether or not the new re­sults will change the agency’s mind re­gard­ing this in­di­ca­tion, giv­en Mer­ck says the EFS da­ta are now good to go. OS is a sec­ondary end­point in this study, and Mer­ck did not dis­close any re­lat­ed in­for­ma­tion in Thurs­day’s an­nounce­ment.

At least one an­a­lyst thinks Thurs­day’s an­nounce­ment will ul­ti­mate­ly set up Mer­ck for a re­bound at the FDA. Bar­clays’ Carter Gould wrote to in­vestors that al­though there were no quan­ti­ta­tive da­ta re­leased, Mer­ck could see a po­ten­tial ap­proval as ear­ly as next year.

“These da­ta should di­rect­ly ad­dress the pan­el’s re­cent con­cern over the lack of ma­ture EFS da­ta, and we would ex­pect Mer­ck to re­file based on these da­ta,” Gould wrote. “This shouldn’t be sur­pris­ing as Mer­ck it­self high­light­ed dur­ing the Ad­Com that the study had 75-95%+ chance of demon­strat­ing a sta­tis­ti­cal­ly sig­nif­i­cant ben­e­fit based on its mod­el­ing as­sump­tions at the time.”

Even though Keytru­da has be­come one of the best-sell­ing drugs on the plan­et, bring­ing in al­most $3.9 bil­lion in this year’s first quar­ter, high-risk TNBC has proven a rare stum­bling block for Mer­ck. Be­fore the ad­comm re­buff, Keytru­da had al­ready come up short to Roche’s ri­val Tecen­triq in pa­tients with PD-L1-ex­press­ing TNBC that have un­re­sectable and lo­cal­ly re­cur­rent or metasta­t­ic tu­mors. Mer­ck even­tu­al­ly gained the thumbs up here last No­vem­ber.

But Tecen­triq pre­vi­ous­ly failed a con­fir­ma­to­ry study for the first-line treat­ment of the PD-L1 group, which may end up putting its ac­cel­er­at­ed ap­proval in jeop­ardy. ODAC vot­ed 7 to 2 in April to main­tain its OK, how­ev­er, as part of the FDA’s broad­er re­view of ac­cel­er­at­ed ap­provals that missed their pri­ma­ry end­points in the con­fir­ma­to­ry fol­low-ups.

So­cial: Va­leriya Zankovych/Shut­ter­stock

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

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Cy­to­ki­net­ics’ ALS drug fails PhI­II, leav­ing the biotech with a sin­gle late-stage prospect

Cytokinetics’ candidate for the muscle disease amyotrophic lateral sclerosis, or ALS, failed a Phase III trial, the Bay Area biotech announced Friday morning.

At a second interim analysis of the trial, an independent review committee recommended that Cytokinetics discontinue its COURAGE-ALS trial for reldesemtiv, as it “found no evidence of effect” compared to placebo on the primary or key secondary endpoints.

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CHMP gives thumbs-up for We­govy use in ado­les­cents, along with nine new drug rec­om­men­da­tions

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) recommended nine drugs for approval this week while also giving thumbs up for six expanded indications, including Novo Nordisk’s approved obesity medication Wegovy for younger people. Wegovy is already approved as an obesity treatment in the EU for adults, and the new indication would allow prescriptions for adolescents aged 12 and older.

Austin biotech Mol­e­c­u­lar Tem­plates lays off more than 100 staffers as pipeline nar­rows

Molecular Templates is ridding itself of a Phase I HER2 asset and fine-tuning its pipeline to focus on three programs and a preclinical Bristol Myers Squibb collaboration. With the narrowed scope on its so-called engineered toxin bodies, the Austin, TX biotech is laying off about half of its staff.

That’s a little more than 100 employees, per an SEC filing. Molecular’s layoffs, approved by its board Wednesday, add to the dozens of pullbacks in the industry in the first three months of 2023.

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Mathai Mammen, FogPharma's next CEO

Math­ai Mam­men hands in J&J's R&D keys to lead Greg Ver­dine’s Fog­Phar­ma 

In the early 1990s, Mathai Mammen was a teaching assistant in Greg Verdine’s Science B46 course at Harvard. In June, the former R&D head at Johnson & Johnson will succeed Verdine as CEO, president and chair of FogPharma, the same month the seven-year-old biotech kickstarts its first clinical trial.

After leading R&D at one of the largest drugmakers in the world, taking the company through more than half a dozen drug approvals in the past few years, not to mention a Covid-19 vaccine race, Mammen departed J&J last month and will take the helm of a Cambridge, MA biotech attempting to go after what Verdine calls the “true emperor of all oncogenes” — beta-catenin.

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Green­Light re­ceives buy­out of­fer; Apol­lomics com­pletes SPAC merg­er

RNA biotech GreenLight Biosciences has been handed an offer for potential acquisition.

GreenLight said in a release that it has received a non-binding “indication of interest” from Fall Line Endurance Fund to acquire GreenLight’s capital stock for $0.60 per share in cash. The release said any potential agreement between the two parties would depend on certain conditions.

Through a special committee, the biotech will evaluate the offer but added there’s no certainty a deal will go forward. GreenLight will also not make any more announcements until a deal comes through or “otherwise determines” a statement is necessary.

TScan Therapeutics' departing CEO David Southwell and CSO/COO Gavin MacBeath

TCR up­start an­nounces CEO ex­it, with CSO now act­ing re­place­ment

A public T cell biotech’s chief executive has decided to leave the company.

TScan Therapeutics said Friday morning that CEO David Southwell stepped down earlier this week, leaving both his chief executive and board member roles. Filling in is Gavin MacBeath, the company’s CSO and COO. He became the acting CEO on Tuesday, and will continue to remain CSO and COO, TScan’s announcement read.

Aptinyx eval­u­ates fu­ture of the com­pa­ny fol­low­ing two failed tri­als, 60% lay­offs

This year has been tough for Aptinyx — two failed trials, a 60% cut in its workforce, and now the company has brought on a firm to help evaluate the future of the company.

The press release noted it’s working with the firm Ladenburg Thalmann as its financial advisor to assist in exploring and evaluating “strategic alternatives” — a process that a growing group of struggling biotechs has embarked on, sometimes ending in a merger, asset sale or wind-down.

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Sar­to­rius to ac­quire French man­u­fac­tur­er for $2.6B+ in cell and gene ther­a­py play

The German life science group Sartorius will be picking up French contract manufacturer Polyplus for the price of €2.4 billion, or $2.6 billion.

On Friday, Sartorius announced the acquisition through its French subgroup, Sartorius Stedim Biotech, which will be acquiring Polyplus from private investors ARCHIMED and WP GG Holdings IV. Polyplus has 270 employees and produces materials and components that go into making viral vectors that are used in cell and gene therapies. This includes DNA/RNA reagents as well as plasmid DNA. Polyplus has locations in France, Belgium, China and the US.