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

Health­care Dis­par­i­ties and Sick­le Cell Dis­ease

In the complicated U.S. healthcare system, navigating a serious illness such as cancer or heart disease can be remarkably challenging for patients and caregivers. When that illness is classified as a rare disease, those challenges can become even more acute. And when that rare disease occurs in a population that experiences health disparities, such as people with sickle cell disease (SCD) who are primarily Black and Latino, challenges can become almost insurmountable.

Jacob Van Naarden (Eli Lilly)

Ex­clu­sives: Eli Lil­ly out to crash the megablock­buster PD-(L)1 par­ty with 'dis­rup­tive' pric­ing; re­veals can­cer biotech buy­out

It’s taken 7 years, but Eli Lilly is promising to finally start hammering the small and affluent PD-(L)1 club with a “disruptive” pricing strategy for their checkpoint therapy allied with China’s Innovent.

Lilly in-licensed global rights to sintilimab a year ago, building on the China alliance they have with Innovent. That cost the pharma giant $200 million in cash upfront, which they plan to capitalize on now with a long-awaited plan to bust up the high-price market in lung cancer and other cancers that have created a market worth tens of billions of dollars.

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So what hap­pened with No­var­tis' gene ther­a­py group? Here's your an­swer

Over the last couple of days it’s become clear that the gene therapy division at Novartis has quietly undergone a major reorganization. We learned on Monday that Dave Lennon, who had pursued a high-profile role as president of the unit with 1,500 people, had left the pharma giant to take over as CEO of a startup.

Like a lot of the majors, Novartis is an open highway for head hunters, or anyone looking to staff a startup. So that was news but not completely unexpected.

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Who are the women su­per­charg­ing bio­phar­ma R&D? Nom­i­nate them for this year's spe­cial re­port

The biotech industry has faced repeated calls to diversify its workforce — and in the last year, those calls got a lot louder. Though women account for just under half of all biotech employees around the world, they occupy very few places in C-suites, and even fewer make it to the helm.

Some companies are listening, according to a recent BIO survey which showed that this year’s companies were 2.5 times more likely to have a diversity and inclusion program compared to last year’s sample. But we still have a long way to go. Women represent just 31% of biotech executives, BIO reported. And those numbers are even more stark for women of color.

David Meek, new Mirati CEO (Marlene Awaad/Bloomberg via Getty Images)

Fresh off Fer­Gene's melt­down, David Meek takes over at Mi­rati with lead KRAS drug rac­ing to an ap­proval

In the insular world of biotech, a spectacular failure can sometimes stay on any executive’s record for a long time. But for David Meek, the man at the helm of FerGene’s recent implosion, two questionable exits made way for what could be an excellent rebound.

Meek, most recently FerGene’s CEO and a past head at Ipsen, has become CEO at Mirati Therapeutics, taking the reins from founding CEO Charles Baum, who will step over into the role of president and head of R&D, according to a release.

Volker Wagner (L) and Jeff Legos

As Bay­er, No­var­tis stack up their ra­dio­phar­ma­ceu­ti­cal da­ta at #ES­MO21, a key de­bate takes shape

Ten years ago, a small Norwegian biotech by the name of Algeta showed up at ESMO — then the European Multidisciplinary Cancer Conference 2011 — and declared that its Bayer-partnered targeted radionuclide therapy, radium-223 chloride, boosted the overall survival of castration-resistant prostate cancer patients with symptomatic bone metastases.

In a Phase III study dubbed ALSYMPCA, patients who were treated with radium-223 chloride lived a median of 14 months compared to 11.2 months. The FDA would stamp an approval on it based on those data two years later, after Bayer snapped up Algeta and christened the drug Xofigo.

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Mi­rati tri­umphs again in KRAS-mu­tat­ed lung can­cer with a close­ly watched FDA fil­ing now in the cards

After a busy weekend at #ESMO21, which included a big readout for its KRAS drug adagrasib in colon cancer, Mirati Therapeutics is ready to keep the pressure on competitor Amgen with lung cancer data that will undergird an upcoming filing.

In topline results from a Phase II cohort of its KRYSTAL-1 study, adagrasib posted a response rate of 43% in second-line-or-later patients with metastatic non-small cell lung cancer containing a KRAS-G12C mutation, Mirati said Monday.

When ef­fi­ca­cy is bor­der­line: FDA needs to get more con­sis­tent on close-call drug ap­provals, agency-fund­ed re­search finds

In the exceedingly rare instances in which clinical efficacy is the only barrier to a new drug’s approval, new FDA-funded research from FDA and Stanford found that the agency does not have a consistent standard for defining “substantial evidence” when flexible criteria are used for an approval.

The research comes as the FDA is at a crossroads with its expedited-review pathways. The accelerated approval pathway is under fire as the agency recently signed off on a controversial new Alzheimer’s drug, with little precedent to explain its decision. Meanwhile, top officials like Rick Pazdur have called for a major push to simplify and clarify all of the various expedited pathways, which have grown to be must-haves for sponsors of nearly every newly approved drug.

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Ted White, Verrica CEO

Ver­ri­ca hits an­oth­er bump in the road with CMO re­lat­ed let­ter from FDA

The FDA has rejected Verrica’s new drug application for VP-102 again, with the company pinning the CRL on problems at a CMO that it was partnered with, the company announced Monday.

The FDA didn’t raise issues that directly relate to the manufacturing of VP-102, the company said, but raised “general quality issues” at the CMO’s facility. There were also no clinical concerns, it said, or need to collect more data.