Take­da earns win for its TKI in­hibitor in tiny lung can­cer group — but GI side ef­fects could be an ear­ly red flag

Japan­ese drug­mak­er Take­da has made a big push in re­cent years to build a hand in on­col­o­gy, par­tic­u­lar­ly in the next-gen can­cer space. One of those can­di­dates, ty­ro­sine ki­nase in­hibitor (TKI) mobo­cer­tinib, re­cent­ly earned the FDA’s in­ter­est in a small sec­tion of un­treat­ed lung can­cer pa­tients, but will se­vere GI side ef­fects be a road­block?

Take­da’s oral mobo­cer­tinib post­ed clin­i­cal­ly sig­nif­i­cant ob­jec­tive re­sponse rates in a Phase I/II adap­tive tri­al drug­ging metasta­t­ic non-small cell lung can­cer pa­tients with EGFR ex­on 20 gene mu­ta­tions who had pre­vi­ous­ly un­der­gone plat­inum-based chemother­a­py, ac­cord­ing to da­ta pre­sent­ed Thurs­day at the vir­tu­al World Con­fer­ence on Lung Can­cer.

Pa­tients re­ceiv­ing mobo­cer­tinib hit an ORR of 35% as judged by the tri­al’s in­ves­ti­ga­tors and 28% from an in­de­pen­dent da­ta re­view com­mit­tee. The drug al­so showed a me­di­an du­ra­tion of re­sponse of 17.5 months — both in­ves­ti­ga­tors and the DRC agreed on that fig­ure — and pro­gres­sion-free sur­vival of 7.3 months.

Chris Arendt

Ac­cord­ing to Chris Arendt, Take­da’s head of on­col­o­gy, the pooled re­sults show promise for ex­on 20-pos­i­tive pa­tients, who make up about 10% of the to­tal EGFR NSCLC pop­u­la­tion and have a par­tic­u­lar­ly poor prog­no­sis. De­spite the sin­gle-fig­ure gap be­tween in­ves­ti­ga­tors’ and the com­mit­tee’s find­ings, Arendt told End­points News his team didn’t view the dif­fer­ence as mean­ing­ful giv­en “a bit of a wob­ble” in terms of judg­ing re­sponse.

It’s a small pop­u­la­tion but one with a high un­met clin­i­cal need. Mobo­cer­tinib earned the FDA’s break­through des­ig­na­tion tag back in April for sec­ond-line use af­ter plat­inum-based chemo and is look­ing to bring the drug in­to the first-line use in fur­ther tri­als.

But it wasn’t all ros­es for Take­da’s drug. In­ves­ti­ga­tors not­ed a high rate of se­vere di­ar­rhea in tri­al pa­tients — enough so that they in­sti­tut­ed a di­ar­rhea man­age­ment pro­to­col for pa­tients in the Phase I por­tion of the tri­al and con­tin­ued in the Phase II ex­pan­sion. In all, di­ar­rhea was re­port­ed in 90% of all pa­tients with se­vere side ef­fects, fol­lowed by rash at 45%. Nine­teen per­cent of the study’s 114 pa­tients dropped out, with di­ar­rhea and nau­sea tagged as the most com­mon cause.

See­ing those GI side ef­fects ear­ly, Take­da’s in­ves­ti­ga­tors in­sti­tut­ed a di­ar­rhea pro­to­col that Arendt de­clined to out­line. He said the drug­mak­er would use those guide­lines in fu­ture tri­als and would like­ly file for reg­u­la­to­ry ap­proval to in­clude the pro­to­col on mobo­cer­tinib’s po­ten­tial la­bel. Even with the guide­lines in place, the vast ma­jor­i­ty of pa­tients with se­vere side ef­fects re­port­ed di­ar­rhea, like­ly in­di­cat­ing an even high­er rate of di­ar­rhea in pa­tients who didn’t re­ceive the pro­to­col.

When asked to clar­i­fy the rate of di­ar­rhea in pa­tients pri­or to those guide­lines be­ing put in place, Arendt “cau­tion(ed) a lit­tle bit in terms of over-in­ter­pret­ing” and said the pro­to­col was de­signed to be “avail­able to pa­tients and not oner­ous.” The drug­mak­er plans to present fur­ther de­tails on those guide­lines at a lat­er date, Arendt said, and not­ed that se­vere di­ar­rhea was com­mon in ex­on 20-pos­i­tive pa­tients af­ter chemo.

With Phase II da­ta in hand, Take­da is work­ing on fil­ing mobo­cer­tinib’s ap­pli­ca­tion with the FDA for sec­ond-line use and is al­so gun­ning for ear­li­er use in ex­on 20-pos­i­tive pa­tients, Arendt said. The drug­mak­er is look­ing to con­firm its Phase II find­ings on the glob­al lev­el and has earned a break­through tag in Chi­na to speed de­vel­op­ment there.

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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