In the bat­tle against kid­ney can­cer, Mer­ck­'s key­stone im­munother­a­py Keytru­da edges in front

Mer­ck $MRK may not just have a leg up over Bris­tol-My­ers Squibb $BMY in the lu­cra­tive field of lung can­cer. It looks like the com­pa­ny’s block­buster check­point in­hibitor Keytru­da — large­ly con­sid­ered the pre­em­i­nent im­munother­a­py — is on its way to es­tab­lish­ing its edge in re­nal can­cer. Ahead of the Gen­i­touri­nary (GU) Can­cers Sym­po­sium lat­er this week, an ab­stract de­tail­ing the re­sults of a piv­otal study test­ing a Keytru­da com­bi­na­tion in pre­vi­ous­ly un­treat­ed re­nal cell car­ci­no­ma (RCC) pa­tients ce­ment­ed the PD-1 drug’s lead­ing sta­tus.

Topline da­ta re­leased last Oc­to­ber showed a com­bi­na­tion of Keytru­da and Pfiz­er’s $PFE ty­ro­sine ki­nase in­hibitor (TKI) In­ly­ta in the KEYNOTE-426 tri­al im­proved over­all sur­vival, pro­gres­sion-free sur­vival and over­all re­sponse rates across risk groups and re­gard­less of PD-L1 sta­tus, com­pared to Pfiz­er’s Su­tent, in first-line RCC pa­tients. Mer­ck of­fered fur­ther de­tail on Mon­day, in­di­cat­ing the Keytru­da com­bo sig­nif­i­cant­ly im­proved OS, re­duc­ing the risk of death by near­ly half (HR 0.53), as well as PFS (HR 0.69).

An­a­lysts cheered the da­ta. Cowen an­a­lysts sug­gest­ed that a TKI/IO com­bo will emerge as the stan­dard of care in first line RCC, and that they an­tic­i­pate sim­i­lar re­sults to emerge from the on­go­ing Check­Mate 9ER tri­al, which is test­ing a com­bi­na­tion of Op­di­vo and Ex­elix­is’ $EX­EL TKI Cabome­tyx ver­sus Su­tent in RCC pa­tients.

Keytru­da+In­ly­ta showed im­pres­sive over­all re­sults and will like­ly gain ap­proval in 1L set­ting. While these da­ta may cause some volatil­i­ty in EX­EL stock…the on­go­ing Check­Mate 9ER tri­al should re­port sim­i­lar if not bet­ter re­sults…Cabo re­mains the pre­ferred TKI for RCC based on NC­CN guide­lines. Ad­di­tion­al­ly, we an­tic­i­pate that many physi­cians will view KEYNOTE-426 as a class ef­fect (strong syn­er­gy be­tween TKI and check­point in­hibitor), and this may even re­sult in an in­cre­men­tal in­crease in cabo use in the front­line set­ting with a check­point in­hibitor pri­or to Check­Mate 9ER re­sults and po­ten­tial la­bel ex­pan­sion.

Cred­it Su­isse’s Vi­mal Di­van said the Keytru­da com­bo’s OS haz­ard ra­tio sur­passed ex­pec­ta­tions, con­sid­er­ing in­vestors had an­tic­i­pat­ed a HR around the 0.60 thresh­old.

“Bris­tol-My­ers has been gain­ing share in the 1L RCC mar­ket with their Op­di­vo + Yer­voy com­bo but Mer­ck’s da­ta ap­pears su­pe­ri­or giv­en a low­er OS HR, a pos­i­tive im­pact on PFS and an im­pact be­ing seen across a broad­er pop­u­la­tion. Op­di­vo + Yer­voy showed an OS ben­e­fit (but not a PFS ben­e­fit) over Su­tent in the Check­Mate-214 tri­al but on­ly in in­ter­me­di­ate and high-risk pa­tients and the ben­e­fit, in our view, be­ing dri­ven by the re­spons­es seen in pa­tients that were PD-L1 pos­i­tive. Over time, the avail­abil­i­ty of a gener­ic ver­sion of In­ly­ta (we as­sume in 2025) could al­so pro­vide a cost ad­van­tage for the Keytru­da + In­ly­ta reg­i­men over Op­di­vo + Yer­voy,” Di­van said.

In its fourth-quar­ter earn­ings call, Mer­ck said it has al­ready sub­mit­ted an ap­pli­ca­tion to mar­ket Keytru­da to treat first line RCC pa­tients, but Pfiz­er and Mer­ck KGaA on Mon­day said the FDA had agreed to a speedy re­view for their ap­pli­ca­tion to mar­ket a com­bi­na­tion of their check­point in­hibitor Baven­cio and In­ly­ta in RCC pa­tients — the agency is ex­pect­ed to make its de­ci­sion by June.

“(The) Baven­cio com­bi­na­tion with In­ly­ta may get to mar­ket in the US first, hav­ing been grant­ed pri­or­i­ty re­view by the FDA…based on da­ta from JAVELIN Re­nal 101. How­ev­er, we view Keytru­da + In­ly­ta as like­ly to over­take Baven­cio + In­ly­ta as well giv­en greater physi­cian com­fort with Keytru­da over Baven­cio and the pos­i­tive OS da­ta that KEYNOTE-426 de­liv­ered at the first in­ter­im analy­sis (as com­pared to JAVELIN Re­nal 101 where we on­ly saw a PFS ben­e­fit at the in­ter­im analy­sis),” Di­van added.

UP­DAT­ED: Mer­ck pulls Keytru­da in SCLC af­ter ac­cel­er­at­ed nod. Is the FDA get­ting tough on drug­mak­ers that don't hit their marks?

In what could be an early shot in the battle against drugmakers that whiff on confirmatory studies to support accelerated approvals, the FDA ordered Bristol Myers Squibb late last year to give up Opdivo’s approval in SCLC. Now, Merck is next on the firing line — are we seeing the FDA buckling down on post-marketing offenders?

Merck has withdrawn its marketing approval for PD-(L)1 inhibitor Keytruda in metastatic small cell lung cancer as part of what it describes as an “industry-wide evaluation” by the FDA of drugs that do not meet the post-marketing checkpoints on which their accelerated nods were based, the company said Monday.

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Paul Sekhri

The next big biotech su­per­star? Paul Sekhri has some thoughts on that

It occasionally occurs to Paul Sekhri that if they pull this off, his company will be on the front page of the New York Times and a lead story in just about every major news outlet on the planet. He tries not to dwell on it, though.

“I just want to be laser-focused on getting to that point,” Sekhri says, before acknowledging, “Yes, it absolutely crossed my mind.”

Sekhri, a longtime biopharma executive with tenures at Sanofi and Novartis, is now entering year three as CEO of eGenesis, the biotech that George Church protégé Luhan Yang founded to genetically alter pigs so that they can be used for organ transplants. He led them through one megaround and has just closed another, raising $125 million from 17 different investors to push the first-ever (humanized) pig to human transplants into the clinic.

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Amit Munshi, Arena

One of Are­na's top drugs flops in a PhI­Ib study for IBS pain. But re­searchers tease out a pos­si­ble path for­ward as CEO ex­plores 's­trate­gic op­tion­s'

Four years ago, when Arena CEO Amit Munshi cut its ties to a troubled weight drug and doubled down on the pipeline, a cannabinoid receptor 2 agonist figured prominently in the biotech’s future. On Tuesday evening, however, Munshi’s high hopes for the drug took a nasty hit after it failed a Phase IIb study for patients with irritable bowel syndrome pain.

Put through a randomized pace with 273 patients, researchers said it flat failed the primary endpoint among the large group with abdominal pain. But they quickly went on to highlight subgroup data, always a tricky and controversial ploy, where they spotlighted a positive p value for patients with moderate to severe pain who received the high dose of the drug — one of 3 provided in the study.

Bob Nelsen (Photo by Michael Kovac/Getty Images)

With stars aligned and cash in re­serve, Bob Nelsen's Re­silience plans a makeover at 2 new fa­cil­i­ty ad­di­tions to its drug man­u­fac­tur­ing up­start

Bob Nelsen’s new, state-of-the-art drug manufacturing initiative is taking shape.

Just 3 months after gathering $800 million of launch money, a dream team board and a plan to shake up a field where he found too many bottlenecks and inefficiencies for the era of Covid-19, Resilience has snapped up a pair of facilities now in line for a retooling.

The company has acquired a 310,000-square-foot plant in Boston from Sanofi along with a 136,000-square-foot plant in Ontario to add to a network which CEO Rahul Singhvi says is just getting started on building his company’s operations up. The Sanofi deal comes with a contract to continue manufacturing one of its drugs.

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CEO Marco Taglietti (Scynexis)

'N­ev­er been more ur­gent:' Scynex­is looks to tack­le su­per­bug cri­sis with late-stage read­out for an­ti­fun­gal hope­ful

As the superbug crisis heats up around the world, Scynexis says it has new data from two interim analyses that prove its antifungal has the potential to treat a broad range of infections.

“The need for new anti-infectives capable of fighting the most resistant pathogens has never been more urgent as we confront the ongoing COVID-19 global pandemic,” CEO Marco Taglietti said in a statement.

A spot­light schiz­o­phre­nia drug in Neu­ro­crine's $2B Take­da deal flunks its first ma­jor test. But it's not giv­ing up yet

When Takeda spun out a pipeline of experimental psychiatry drugs to Neurocrine in a $2 billion deal amid a post-merger shakeout, R&D chief Andy Plump described the therapies as “very interesting but still difficult.”

On Tuesday, we got some idea of how difficult.

San Diego-based Neurocrine revealed that one of the three spotlight clinical programs they’d acquired failed the primary endpoint in a Phase II trial for schizophrenia, registering a negative outcome on the change from baseline in the positive and negative syndrome scale/negative symptom factor score (PANSS NSFS).

Af­ter bail­ing on Covid-19 vac­cines, Mer­ck will team up with J&J to pro­duce its shot as part of un­usu­al Big Phar­ma pact

Merck took a big gamble when it opted to jump into the Covid-19 vaccine race late, and made an equally momentous decision to back out in late January. Now, looking to chip in on the effort, Merck reportedly agreed to team up with one of the companies that has already crossed the finish line.

President Joe Biden on Tuesday is expected to announce a partnership between drugmakers Merck and Johnson & Johnson to jointly produce J&J’s recombinant protein Covid-19 vaccine that received the FDA’s emergency use authorization Saturday, the Washington Post reported.

Ab­b­Vie tees up a biotech buy­out af­ter siz­ing up their Parkin­son's drug spun out of Ke­van Shokat's lab

AbbVie has teed up a small but intriguing biotech buyout after looking over the preclinical work it’s been doing in Parkinson’s disease.

The company is called Mitokinin, a Bay Area biotech spun out of the lab of UCSF’s Kevan Shokat, whose scientific explorations have formed the academic basis of a slew of startups in the biotech hub. One of Shokat’s PhD students in the lab, Nicholas Hertz, co-founded Mitokinin using their lab work on PINK1 suggesting that amping up its activity could play an important role in regulating the mitochondrial dysfunction contributing to Parkinson’s disease pathogenesis and progression.

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Fi­bro­Gen shares skid low­er as a sur­prise ad­comm rais­es risks on roxa OK

FibroGen will likely have to delay its US rollout for roxadustat once again.

In an unexpected move, the FDA is convening its Cardiovascular and Renal Drugs Advisory Committee to review the NDA in an advisory committee meeting. The date is yet to be confirmed.

Just a few weeks ago, SVB Leerink analyst Geoffrey Porges predicted that the roxa approval could come ahead of the PDUFA date on March 20 — effusive despite already being let down once by the FDA’s extension of its review back in December. AstraZeneca, which is partnered with FibroGen on the chronic kidney disease-related anemia drug, disclosed regulators had requested further clarifying analyses of clinical data.