No­var­tis punts a late-stage PI3K drug with a wor­ry­ing safe­ty pro­file to one of Chi­na’s up­start biotechs

Just months af­ter a group of re­searchers warned against the fur­ther de­vel­op­ment of a wor­ry­ing PI3K in­hibitor project No­var­tis had been work­ing on, the phar­ma gi­ant li­censed out the glob­al rights to a new­ly ac­tive Chi­nese biotech. 

No­var­tis is the lat­est in a long string of Big Phar­ma play­ers who have de­cid­ed to bow out of a trou­ble­some PI3K de­vel­op­ment pro­gram. But in­stead of drop­ping the drug the Swiss com­pa­ny hand­ed world­wide com­mer­cial rights to the late-stage bu­parlis­ib to one of Chi­na’s new up­start biotechs — rais­ing some thorny is­sues about how ques­tion­able drug as­sets may be passed to new play­ers for a com­mer­cial roll­out.

An­ge­lo Di Leo

Late last year a group of sci­en­tists pub­lished a re­port in The Lancet — fund­ed by No­var­tis — that con­clud­ed the drug’s safe­ty pro­file “does not sup­port its fur­ther de­vel­op­ment” in breast can­cer. The group was led by An­ge­lo Di Leo of Nuo­vo Os­pedale di Pra­to San­to Ste­fano in Pra­to, Italy.

The Chi­nese com­pa­ny is Ad­lai Nortye, based in Hangzhou. There’s no word on the terms here, but there has been a con­sid­er­able amount of mar­gin­al ef­fi­ca­cy and wor­ry­ing safe­ty da­ta on dis­play. 

In a study called Belle-3 which com­bined bu­parlis­ib with ful­ves­trant, re­searchers found that there was a pos­i­tive ben­e­fit in pro­gres­sion-free sur­vival: 3.9 months com­pared to 1.8 months for a mar­gin­al but sig­nif­i­cant ad­van­tage for pa­tients.

Grade 3/4 ad­verse events were re­port­ed in close to two out of three pa­tients in the drug arm, com­pared to 34% in the con­trol group. Se­ri­ous ad­verse events, though, were re­port­ed in 22% of the drug arm, com­pared to 16% in the con­trol group, with one treat­ment-re­lat­ed death to re­port in each arm. There were al­so three sui­cide at­tempts in the bu­parlis­ib group, rais­ing con­cerns about sui­ci­dal ideation among pa­tients ex­posed to the drug. Ruth O’Re­gan of the Uni­ver­si­ty of Wis­con­sin-Madi­son has raised con­cerns about the sui­cide at­tempts, not­ing that  “transam­i­nase el­e­va­tions and mood dis­or­ders in pa­tients on this drug may rep­re­sent a clin­i­cal­ly rel­e­vant chal­lenge.”

Ruth O’Re­gan

The re­searchers al­so not­ed in The Lancet that the work may have warned them off the drug for this set­ting, but con­clud­ed that “PI3K in­hibitors plus en­docrine ther­a­py in pa­tients with PIK3CA mu­ta­tions” is a promis­ing area of re­search.

The PI3K field has been plagued by safe­ty con­cerns and weak ef­fi­ca­cy. Roche dumped taselis­ib a few weeks ago at the end of a dis­ap­point­ing Phase III. Gilead’s pi­o­neer­ing Zy­delig got slapped with a black box warn­ing on se­ri­ous and some­times fa­tal tox­i­c­i­ties, forc­ing an end to its quest to com­plete front­line tri­als. Bay­er’s Aliqopa (co­pan­lis­ib) was ap­proved last fall for fol­lic­u­lar lym­phoma pa­tients, crowd­ing a field that Ve­rastem hopes to join with du­velis­ib, a PI3K dropped by In­fin­i­ty Phar­ma­ceu­ti­cals af­ter Ab­b­Vie walked away af­ter get­ting a glimpse of unim­pres­sive — but still ap­prov­able — re­sults. And now not­ed can­cer re­searcher Sid­dhartha Mukher­jee is be­gin­ning a hu­man study to de­ter­mine if a ke­to­genic di­et can close a feed­back loop that de­feats these drugs’ abil­i­ty to fight can­cer.

In its re­lease, Ad­lai Nortye doesn’t men­tion the breast can­cer study, or what kind of com­mer­cial prospects it has in an al­ready well de­vel­oped field. The com­pa­ny did, though, high­light “promis­ing ef­fi­ca­cy in com­bi­na­tion with pa­cli­tax­el in head and neck squa­mous cell car­ci­no­ma” and the fact that the drug “has re­ceived a Fast-Track des­ig­na­tion from the FDA.”

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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Michael Shpigelmacher

Khosla joins bet on un­con­ven­tion­al start­up look­ing to send drug de­liv­er­ing ro­bots in­to the brain

When Michael Shpigelmacher started the project, he knew he’d have to fund it himself. Every other effort of its kind was academic, rejected as too risky by investors.

Shpigelmacher, a robotics geek and entrepeneur who had drifted into consulting for pharma, wanted to build the real-life equivalent of technology from the 1960s film Fantastic Voyage, the one where a submarine crew is shrunk to “about the size of a microbe” and sent on a mission to repair a scientist’s brain. He scanned the literature, found the lab that was working on the most advanced project — at the Max Planck Institute in Germany, it turned out — and started funding them with money from his own account, along with some seed cash from friends and family.

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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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.