Trou­bled by deaths, FDA or­ders Mer­ck to slam the brakes on three Keytru­da stud­ies

Roger Perl­mut­ter, Mer­ck

A month af­ter Mer­ck flagged a high­er risk of death in two com­bo stud­ies us­ing its flag­ship drug Keytru­da, the FDA has fol­lowed up with a clin­i­cal hold that will slam the brakes on fur­ther treat­ment in three mul­ti­ple myelo­ma tri­als.

Mer­ck said a few weeks ago that it planned to con­tin­ue treat­ment in the two stud­ies – KEYNOTE 183 and KEYNOTE 185 – while paus­ing en­roll­ment of new pa­tients. Those mul­ti­ple myelo­ma tri­als matched Mer­ck’s block­buster ther­a­py with two drugs from Cel­gene, Po­m­a­lyst and its big drug Revlim­id.

The FDA, though, wants pa­tients tak­en off of Keytru­da in the two Phase III stud­ies and al­so or­dered Mer­ck to stop treat­ing pa­tients in KEYNOTE-023 Co­hort 1, match­ing Keytru­da in com­bi­na­tion with lenalido­mide and dex­am­etha­sone in pa­tients who re­ceived pri­or an­ti-mul­ti­ple myelo­ma treat­ment with an im­munomod­u­la­to­ry (IMiD) treat­ment (lenalido­mide, po­ma­lido­mide or thalido­mide).

The lat­est news com­pounds a new headache for Mer­ck just as it was putting some se­ri­ous dis­tance be­tween it­self and Bris­tol-My­ers Squibb’s trou­bled ri­val PD-1 drug Op­di­vo. The phar­ma gi­ant notes that these are the on­ly three tri­als – among dozens in the clin­ic – that are af­fect­ed by the agency’s de­ci­sion. Mer­ck has nev­er of­fered an ex­pla­na­tion, or the­o­ry, about the high­er risk of deaths in these com­bi­na­tion stud­ies.

Mer­ck shares were down about 1% in af­ter-mar­ket trad­ing.

The clin­i­cal hold al­so rais­es ques­tions about some of the oth­er com­bi­na­tion stud­ies in the clin­ic. Ever­core ISI’s Umer Raf­fat notes:

It will be very in­ter­est­ing to see the fate of BMY’s Check­mate-602 (ni­vo + pom/dex) as well as Cel­gene/AZN’s FU­SION­MM-03 of dur­va+dara+pom/dex in mul­ti­ple myelo­ma. Here’s what we know at present:  BMY tri­al was ini­ti­at­ed ~6 months af­ter MRK’s un­suc­cess­ful myelo­ma tri­als … and the Cel­gene/AZN tri­al was ini­ti­at­ed ~9 months af­ter MRK’s

“Pa­tient safe­ty is Mer­ck’s pri­ma­ry con­cern, and we are grate­ful to the study in­ves­ti­ga­tors and pa­tients in­volved in these stud­ies for their com­mit­ment to this im­por­tant re­search,” said Roger Perl­mut­ter, pres­i­dent, Mer­ck Re­search Lab­o­ra­to­ries. “Mer­ck’s de­vel­op­ment pro­gram for KEYTRU­DA, span­ning more than 30 dif­fer­ent tu­mor types, has one pri­or­i­ty: help­ing pa­tients suf­fer­ing from can­cer.”

Mi­no­ryx and Sper­o­genix ink an ex­clu­sive li­cense agree­ment to de­vel­op and com­mer­cial­ize lerigli­ta­zone in Chi­na

September 23, 2020 – Hong Kong, Beijing, Shanghai (China) and Mataró, Barcelona (Spain)  

Minoryx will receive an upfront and milestone payments of up to $78 million, as well as double digit royalties on annual net sales 

Sperogenix will receive exclusive rights to develop and commercialize leriglitazone for the treatment of X-linked adrenoleukodystrophy (X-ALD), a rare life-threatening neurological condition

President Trump walks past HHS secretary Alex Azar (Getty Images)

Azar falls in line un­der Trump again. Ex­perts say he's re­in­forc­ing a dark sig­nal sent to the FDA

In the latest incident where Alex Azar has steadfastly taken the side of President Donald Trump over that of the FDA, the HHS secretary was noncommittal this morning when asked if he supports the attempt by his subordinates at the FDA to strengthen guidelines for a vaccine EUA.

Appearing on NBC’s Today Show, the HHS secretary muddied the waters, stating that the guidance that matters is the one that is “actually already out there.”

Vas Narasimhan (AP Images)

UP­DAT­ED: Still held down by clin­i­cal hold, No­var­tis' Zol­gens­ma falls fur­ther be­hind Bio­gen and Roche as FDA asks for a new piv­otal study

Last October, the FDA slowed down Novartis’ quest to extend its gene therapy to older spinal muscular atrophy patients by slapping a partial hold on intrathecal administration. Almost a year later, the hold is still there, and regulators are adding another hurdle required for regulatory submission: a new pivotal confirmatory study.

The new requirement — which departs significantly from Novartis’ prior expectations — will likely stretch the path to registration beyond 2021, when analysts were expecting a BLA submission. That could mean more time for Biogen to reap Spinraza revenues and Roche to ramp up sales of Evrysdi in the absence of a rival.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 90,500+ biopharma pros reading Endpoints daily — and it's free.

New York governor Andrew Cuomo (AP Images)

An­drew Cuo­mo says New York will un­der­take its own vac­cine re­view process, and wouldn’t rec­om­mend trust­ing the fed­er­al gov­ern­ment

The concerns keep mounting over President Donald Trump’s politicization of the FDA and other federal agencies guiding the development of a safe and effective vaccine. And today, the telegenic New York governor Andrew Cuomo appeared to introduce even more politics into the matter — latest in an ongoing series of incidents that have cast the proudly independent FDA in starkly political terms.

During his daily press conference Cuomo said that the state will review any coronavirus vaccines approved by the federal government, citing a lack of trust of the Trump administration. The announcement comes one day after Trump accused the FDA of making an “extremely political” move in proposing stricter vaccine guidance.

Laura Shawver (Silverback Therapeutics)

Fol­low­ing a hefty Se­ries B, Sil­ver­back Ther­a­peu­tics quick­ly pulls in $85M for 'an im­por­tant growth phase'

Months after reeling in a $78 million Series B round, Silverback Therapeutics has hooked an even larger Series C.

The Seattle-based company announced Wednesday that it netted $85 million from a slate of new and previous investors. The quick boost could be a sign that an IPO is on the way.

In an email, Silverback CEO Laura Shawver told me she was “not able to provide any additional comments about Silverback” beyond what was shared in the company’s news release. In the prepared statement, she said the company is at “an important growth phase.”

PhII Alzheimer's fail­ure deals new blow to Roche, AC Im­mune — but the tau hy­poth­e­sis is far from dead

The leading anti-tau antibody has failed its first Phase II testing, casting a shadow on a popular target (just trailing amyloid beta) for Alzheimer’s disease.

Roche and AC Immune are quick to acknowledge disappointment in the topline readout, which suggested that semorinemab did not reduce cognitive decline among patients with early Alzheimer’s disease, who are either just starting to have symptoms or have mild manifestations.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 90,500+ biopharma pros reading Endpoints daily — and it's free.

Covid-19 roundup: Op­er­a­tion Warp Speed's 7th vac­cine is live at­ten­u­at­ed; Small biotech touts big suc­cess where gi­ants have failed

Operation Warp Speed is stacking its vaccine portfolio with a “TBD” new candidate: a live attenuated vaccine that can be administered in a single dose, potentially as an oral formulation rather than an injection.

Sound familiar?

That could be because the unannounced candidate appears to match the profile of an inoculation being developed by Merck, according to Bloomberg, which first reported the development based on a presentation by Moncef Slaoui.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 90,500+ biopharma pros reading Endpoints daily — and it's free.

On­ly five months af­ter a Se­ries A launch, Taysha goes pub­lic with $157M IPO

As has been the trend in 2020, Taysha Gene Therapies has become the latest biotech to make a quick ascent from a small, privately-funded company to enjoying its very own Nasdaq ticker.

The Dallas-based biotech raised $157 million for its IPO after pricing shares at $20 apiece Thursday, the high-point of its expected range. Initially pegging $100 million in financing, Taysha offered a little less than 8 million shares and will trade under the $TSHA symbol.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 90,500+ biopharma pros reading Endpoints daily — and it's free.

CDC’s Robert Redfield, NIAID’s Anthony Fauci, Admiral Brett Giroir at HHS, and FDA’s Stephen Hahn prepare to testify at a House hearing on June 23 (Getty)

'Ex­treme­ly po­lit­i­cal' — Trump neuters FDA's at­tempt to strength­en vac­cine EUA

Stephen Hahn went before a Senate committee Wednesday and declared he’s fighting. “Every one of the decisions we have reached has been made by career FDA scientists based on science and data, not politics,” he exclaimed, adding that “FDA will not permit any pressure from anyone to change that. I will fight for science.”

A few hours later, he was undermined by President Donald Trump when a reporter asked if he was okay with stricter vaccine guidelines that the FDA was said to be cooking up. “That has to be approved by the White House. We may or may not approve it. That sounds like a political move,” he decided.