NASH con­tender CymaBay runs in­to trou­ble as mid-stage da­ta dis­ap­point

A snap­shot of neg­a­tive da­ta from an on­go­ing 52-week mid-stage NASH study eval­u­at­ing CymaBay Ther­a­peu­tics’ lead drug has trig­gered alarm, af­ter the ex­per­i­men­tal liv­er drug, se­ladel­par, per­formed worse than a place­bo at a three-month read­out.

Sur­prised and aghast, in­vestors of the San Fran­cis­co-based biotech wast­ed lit­tle time in reg­is­ter­ing their dis­ap­point­ment. The com­pa­ny’s shares $CBAY plum­met­ed about 44.5% to $6.16 in ear­ly Tues­day trad­ing.

In the 181-pa­tient tri­al, pa­tients were ei­ther giv­en place­bo, se­ladel­par 10 mg, 20 mg, or 50 mg once dai­ly. The main goal at the end of 12 weeks was to in­duce a sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment in liv­er fat con­tent. Pa­tients giv­en the place­bo saw a re­duc­tion of 20.8% in liv­er fat, while those giv­en the three es­ca­lat­ing dos­es of se­ladel­par ex­pe­ri­enced small­er im­prove­ments: 10 mg (9.8%), 20 mg (14.2%) and 50 mg (13%).

Cymabay has pre­vi­ous­ly said it ex­pect­ed to see a 20-30% rel­a­tive — place­bo-ad­just­ed — change in liv­er fat at 12 weeks.

Pol Boudes Linkedin

“While the re­duc­tions in liv­er fat were min­i­mal, we re­main en­cour­aged by the sig­nif­i­cant im­prove­ments in bio­chem­i­cal mark­ers of liv­er in­jury…” Pol Boudes, CymaBay’s chief med­ical of­fi­cer, said in a state­ment.

The ex­per­i­men­tal drug’s 52-week biop­sy read­out is ex­pect­ed in mid-2020. Se­ladel­par be­longs to a fam­i­ly of drugs that ac­ti­vate pro­teins called per­ox­i­some pro­lif­er­a­tor-ac­ti­vat­ed re­cep­tors (PPARs), which reg­u­late gene ex­pres­sion. Ex­ist­ing ev­i­dence sug­gests that in the liv­er, PPAR ag­o­nists play a role in bile acid syn­the­sis, in­flam­ma­tion, fi­bro­sis and lipid me­tab­o­lism.

“While there is still a 52-week fol­low-up, we be­lieve that these 12-week re­sults sig­nif­i­cant­ly lessen the com­pet­i­tive threat of se­ladel­par in NASH. Hence, by less­en­ing the com­pet­i­tive threat, we be­lieve these re­sults should ben­e­fit In­ter­cept, as OCA re­mains the on­ly med­ica­tion to show a ben­e­fit on fi­bro­sis in a Phase 3 tri­al. While OCA has some is­sues of its own, we think it is no­table that one of those is NOT a failed ran­dom­ized, place­bo con­trolled study,” Baird’s Bri­an Sko­r­ney wrote in a note.

Akin to CymaBay, French drug de­vel­op­ers Gen­fit (set to re­port piv­otal da­ta in 2019) and In­ven­ti­va are work­ing on their own PPAR ag­o­nists for NASH.

On Tues­day morn­ing, shares of Gen­fit $GN­FT — that re­cent­ly made its Nas­daq de­but — were al­so down about 15% at $20.37. The move­ment like­ly re­flects in­vestors tak­ing the CymaBay da­ta as ev­i­dence against the ef­fi­ca­cy of Gen­fit’s elafi­bra­nor, Sko­r­ney not­ed. “We think this move is some­what un­jus­ti­fied…the two med­ica­tions were thought to have dif­fer­en­ti­at­ed mech­a­nisms of ac­tion, it seems that this may not be the case, as se­ladel­par’s da­ta sug­gest that the med­ica­tion does not re­duce liv­er fat, which is sim­i­lar to what we have seen from ear­li­er tri­als of elafi­bra­nor.”

How­ev­er, as a con­se­quence of the new CymaBay da­ta, the two PPAR ag­o­nists now look more sim­i­lar than dif­fer­ent, he said. “CymaBay may be at a sig­nif­i­cant dis­ad­van­tage mov­ing for­ward as we be­lieve that even if PPAR ag­o­nism is suc­cess­ful in Gen­fit’s Phase 3 tri­al, with­out any clear signs of dif­fer­en­ti­a­tion, CymaBay may have an up­hill bat­tle as they work to catch up to Gen­fit in NASH. If elafi­bra­nor fails in NASH, it would prob­a­bly be pre­dic­tive of the out­come of se­ladel­par in NASH. Ei­ther way, we think this makes the PPAR class, as a whole, look like a less sig­nif­i­cant com­pet­i­tive threat to OCA.”

Oth­er ma­jor NASH con­tenders — Gilead $GILD (fail in Phase III) and In­ter­cept $ICPT (mixed win in Phase III) — have dis­closed the top line num­bers of their late-stage tri­als. In­ter­cept is poised to sub­mit its mar­ket­ing ap­pli­ca­tion lat­er this year.

Im­age: Shut­ter­stock

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.