Liv­er tox cas­es force Dai­ichi Sankyo to cur­tail re­cruit­ment for PhI­II tri­al of a ‘break­through’ drug

Mah­moud Ghazzi

Two cas­es of se­ri­ous liv­er tox­i­c­i­ty forced in­ves­ti­ga­tors to sus­pend en­roll­ment on Dai­ichi Sankyo’s Phase III pro­gram for its “break­through” drug pex­i­dar­tinib (PLX3397). But both cas­es were non-fa­tal, a com­pa­ny spokesper­son tells End­points News, and the tri­al is head­ed to com­ple­tion af­ter the com­pa­ny de­cid­ed to wrap en­roll­ment a few sub­jects short of their goal.

Dai­ichi Sankyo is test­ing the drug on rare cas­es of tenosyn­ovial gi­ant cell tu­mor (TGCT) among pa­tients who couldn’t qual­i­fy for sur­gi­cal re­moval of the tu­mor. By the time the liv­er tox is­sues ap­peared, the com­pa­ny had al­ready en­rolled 121 of the planned 126 pa­tients and the da­ta mon­i­tor­ing com­mit­tee sug­gest­ed cut­ting en­roll­ment short and tak­ing mea­sures so they could pre­serve the study as a dou­ble-blind­ed test.

“As a re­sult,” Dai­ichi said in a state­ment to End­points, “EN­LIV­EN will con­tin­ue to com­ple­tion in or­der to eval­u­ate its ef­fi­ca­cy and safe­ty end­points. These mea­sures were re­viewed and agreed on by the U.S. Food and Drug Ad­min­is­tra­tion (FDA), and all reg­u­la­to­ry au­thor­i­ties in­volved in the EN­LIV­EN study have been no­ti­fied. All pa­tients cur­rent­ly en­rolled in EN­LIV­EN are in the process of be­ing in­formed about this up­dat­ed safe­ty in­for­ma­tion and will un­der­go re-con­sent for con­tin­ued par­tic­i­pa­tion in the study.”

Dai­ichi Sankyo won the FDA’s break­through ther­a­py des­ig­na­tion for the oral CSF-1R in­hibitor based on its Phase I re­sults post­ed last sum­mer. The same tri­al per­suad­ed the Japan­ese phar­ma com­pa­ny to move straight in­to Phase III. That’s an in­creas­ing­ly com­mon clin­i­cal tri­al strat­e­gy.

“Surgery is the pri­ma­ry treat­ment for TGCT, but for pa­tients with a dif­fuse form of the con­di­tion, the tu­mor is more dif­fi­cult to re­move and has a high rate of re­cur­rence, re­sult­ing in mul­ti­ple com­pli­cat­ed surg­eries and even am­pu­ta­tion in some pa­tients,” not­ed Mah­moud Ghazzi, Dai­ichi Sankyo’s for­mer R&D chief, last sum­mer. Ghazzi left the com­pa­ny last month.

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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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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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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Pascal Soriot, AstraZeneca CEO (AP Images)

Pas­cal So­ri­ot cash­es in As­traZeneca’s chips on Mod­er­na for $1.2B cash in­jec­tion

While still working to prove its own Covid-19 vaccine, AstraZeneca has reportedly capitalized on the success of another.

The company has sold off its 7.7% stake in Moderna and turned it into $1.2 billion in cash, according to the Times, beefing up the reserves just as Pascal Soriot is wrapping up his $39 billion acquisition of Alexion and its rare disease pipeline.

AstraZeneca’s stock sale follows a similar move by Merck in December. But like its pharma brethren, the British giant is keeping its R&D collaborations with Moderna.

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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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