CymaBay scraps key NASH, PSC pro­grams af­ter lead drug trig­gers safe­ty alarms — share price im­plodes

When CymaBay Ther­a­peu­tics re­cent­ly ac­knowl­edged de­feat in a 12-week read­out of its Phase II tri­al of se­ladel­par, the biotech grasped at “sig­nif­i­cant im­prove­ments in bio­chem­i­cal mark­ers of liv­er in­jury” as a rea­son to re­main hope­ful about the 52-week biop­sy re­sults. But that hope is now dashed.

Not on­ly did the drug fail to re­duce liv­er fat, it al­so ap­peared to cause cell in­jury.

These “atyp­i­cal his­to­log­i­cal find­ings” — in­clud­ing cas­es of sus­pect­ed in­ter­face he­pati­tis — ob­served in pa­tients who re­spond­ed to their drug forced CymaBay to slam the brakes to its se­ladel­par clin­i­cal pro­gram, ter­mi­nat­ing the Phase IIb study in NASH in ques­tion and a Phase IIa in pri­ma­ry scle­ros­ing cholan­gi­tis (PSC) as well as putting all stud­ies in pri­ma­ry bil­iary cholan­gi­tis on hold.

“We are very dis­ap­point­ed in hav­ing to halt the de­vel­op­ment of se­ladel­par at this time but pa­tient safe­ty and care is para­mount,” CEO Su­jal Shah said in a state­ment.

Shares of the biotech $CBAY, which dipped in the wake of dis­ap­point­ing da­ta in June, are down a fur­ther 76.22% to $1.32 Mon­day morn­ing.

SVB Leerink an­a­lysts called it “a worst case sce­nario el­e­vat­ing safe­ty is­sues that are un­like­ly to be re­solved in the near fu­ture, in our opin­ion.”

“The risk/re­ward clear­ly fa­vors sig­nif­i­cant risk, even as we await ad­di­tion­al in­for­ma­tion and clar­i­ty from CBAY,” they wrote in a note. “Our mod­el is cur­rent­ly un­der re­view.”

But CymaBay’s good day turned out to be a good one for In­ter­cept, which has just clinched pri­or­i­ty re­view and a March 26, 2020 PDU­FA for their NASH drug obeti­cholic acid (OCA).

From Baird’s Bri­an Sko­r­ney:

This fol­lows a long his­to­ry of PPAR ag­o­nists blow­ing up (muragli­tazar, trogli­ta­zone) and high­lights what we be­lieve is an un­der­ap­pre­ci­a­tion of the risks of clin­i­cal de­vel­op­ment in the NASH space. OCA re­mains the on­ly med­ica­tion, to date, that has shown a fi­brot­ic ben­e­fit in a prospec­tive­ly de­fined con­trolled study, and its done it twice. We con­tin­ue to be­lieve OCA is like­ly to be the on­ly game in town for NASH for the fore­see­able fu­ture.

Safe­ty is­sues have pre­vi­ous­ly ben raised in the PPAR ag­o­nist class. This fam­i­ly of drugs ac­ti­vate pro­teins called per­ox­i­some pro­lif­er­a­tor-ac­ti­vat­ed re­cep­tors, which reg­u­late gene ex­pres­sion and are be­lieved to play a role in bile acid syn­the­sis, in­flam­ma­tion, fi­bro­sis and lipid me­tab­o­lism.

Back in 2007 Glax­o­SmithK­line aban­doned its own ef­fort in the field — a col­lab­o­ra­tion with Lig­and Phar­ma­ceu­ti­cals — af­ter their agent led to the for­ma­tion of tu­mors in an­i­mal tests. (The com­pound, GW501516, sub­se­quent­ly took on a sec­ond life as an il­le­gal per­for­mance-en­hanc­ing drug for ath­letes).

France’s Gen­fit and In­ven­ti­va are al­so work­ing on their own PPAR ag­o­nists for NASH. Gen­fit $GN­FT took a small­er toll on CymaBay’s ter­mi­na­tion news than it did fol­low­ing CymaBay’s ini­tial read­out, slid­ing 3.35% to $14.72. Al­most a year ago the drug­mak­er tout­ed that their elafi­bra­nor in­duced a sta­tis­ti­cal­ly sig­nif­i­cant de­crease in serum al­ka­line phos­phatase (ALP) lev­els for PBC pa­tients, and ear­li­er this year it won or­phan sta­tus for that in­di­ca­tion.

While the mar­ket ea­ger­ly awaits Phase III re­sults from Gen­fit, it has al­so se­cured a deal with Terns Phar­ma­ceu­ti­cals to bring the ther­a­py to Chi­na.

On CymaBay’s part, ex­ecs said they are in­ves­ti­gat­ing the sur­prise find­ings, which in­volved pa­tients who “demon­strat­ed on-study im­prove­ment or sta­bi­liza­tion of their bio­chem­i­cal mea­sures of in­flam­ma­tion and liv­er in­jury and no liv­er-re­lat­ed ad­verse events af­ter 52 weeks of treat­ment.”

Biotech in­vestors and CEOs see two paths to growth, but are they equal­ly vi­able?

The dynamic in the biotech market has been highly volatile in the last few years, from the high peaks immediately after the COVID vaccine in 2021, to the lowest downturns of the last 20 years in 2022. This uncertainty makes calling the exact timing of the market’s turn something of a fool’s errand, according to Dr. Chen Yu, Founder and Managing Partner of TCG Crossover (TCG X). He speaks with RBC’s Noël Brown, Head of US Biotechnology Investment Banking, about the market’s road ahead and two possible paths for growth.

Vlad Coric, Biohaven CEO

Vlad Coric charts course for 'New Bio­haven' with neu­ro­science push and Big Phar­ma vets on board

What’s Biohaven without its CGRP portfolio? That’s what CEO Vlad Coric is tasked with deciding as he maps out the “New Biohaven” post-Pfizer takeover.

Pfizer officially scooped up Biohaven’s CGRP assets on Monday, including blockbuster migraine drug Nurtec and the investigational zavegepant, for $11.6 billion. As a result, Coric spun the broader pipeline into an independent company on Tuesday — with the same R&D team behind Nurtec but about 1,000 fewer staffers and a renewed focus on neuroscience and rare disease.

In AstraZeneca's latest campaign, wild eosinophils called Phils personify the acting up often seen in uncontrolled asthma

As­traZeneca de­buts an­noy­ing pur­ple ‘Phil’ crea­tures, per­son­i­fied asth­ma eosinophils ‘be­hav­ing bad­ly’

There are some odd-looking purple creatures lurking around the halls of AstraZenca lately. The “Phil” character cutouts are purple, personified eosinophils with big buggy eyes and wide mouths, and they’re a part of AZ’s newest awareness effort to help people understand eosinophilic asthma.

The “Asthma Behaving Badly” characters aren’t only on the walls at AZ to show the new campaign to employees, however. The “Phils” are also showing up online on the campaign website, and in digital and social ads and posts on Facebook and Instagram.

Casey McPherson shows his daughters Rose (left) and Weston around Everlum Bio, a lab that he co-founded to spark a treatment for Rose and others with ultra-rare conditions. (Ilana Panich-Linsman)

Fa­ther starts lab af­ter in­tel­lec­tu­al prop­er­ty is­sues stymie rare dis­ease drug de­vel­op­ment

Under bright lab lights, Casey McPherson holds his 6-year-old daughter, Rose. His free hand directs Rose’s gaze toward a computer screen with potential clues in treating her one-of-a kind genetic condition.

Gray specks on the screen show her cells that scientists reprogrammed with the goal of zeroing in on a custom medicine. McPherson co-founded the lab, Everlum Bio, to spark a treatment for Rose — and others like her. A regarded singer-songwriter, McPherson never imagined going into drug development.

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Dave Marek, Myovant CEO

My­ovant board balks as ma­jor­i­ty own­er Sum­it­o­mo swoops in with a $2.5B deal to buy them out

Three years after Sumitomo scooped up Roivant’s 46% stake in the publicly traded Myovant $MYOV as part of a 5-company, $3 billion deal, they’re coming back for the whole thing.

But these other investors at Myovant want more than what the Japanese pharma company is currently offering to pay at this stage.

Sumitomo is bidding $22.75 a share for the outstanding stock, which now represents 48% of the company after Sumitomo bumped its ownership since the original deal with Roivant. Myovant, however, created a special committee on the board, and they’re shaking their heads over the offer.

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Ying Huang, Legend CEO

Lentivi­ral vec­tor ramp-up: J&J and Leg­end to in­vest $500M in New Jer­sey man­u­fac­tur­ing to sup­port Carvyk­ti

In response to a question on manufacturing scale at Legend Biotech’s R&D day yesterday, the company’s top exec said its partnership with Johnson & Johnson will be doubling its investment in its New Jersey manufacturing center and will be investing a total of $500 million.

With an eye on their BCMA-directed CAR-T therapy Carvykti (cilta-cel), approved in February as a fifth-line treatment for multiple myeloma, Legend CEO Ying Huang said that the ramp-up in production and the decision to manufacture its own lentiviral vectors — currently in shortage worldwide — means they won’t have to deal with that shortage.

Kite Phar­ma gets FDA to sign off on new Cal­i­for­nia-based vec­tor man­u­fac­tur­ing fa­cil­i­ty

Kite Pharma just got FDA approval to kick off operations at a new manufacturing campus.

The cancer-focused, CAR-T cell therapy player made the announcement Monday, saying that the federal regulatory agency gave the green light to Kite’s 100,000 square-foot, retroviral vector manufacturing facility in Oceanside, CA.

Kite’s global head of technical operations Chris McDonald tells Endpoints News that the facility has been in the works for about four years, after Kite teamed up with its parent company Gilead. Gilead acquired Kite Pharma for just shy of $12 billion in 2017.

Mar­ket­ingRx roundup: No­var­tis re­cruits NFL coach for Leqvio cam­paign; Pfiz­er pro­motes ‘Sci­ence’ merch on so­cial me­dia

Novartis is turning to a winning coach to talk about Leqvio and the struggles of high cholesterol — including his own. Bruce Arians, the retired NFL head coach of the Arizona Cardinals and Super Bowl-winning Tampa Bay Buccaneers, is partnering with the pharma for its “Coaching Cholesterol” digital, social and public relations effort.

In the campaign, Arians talks about the potential for “great comebacks” in football and heart health. Once nicknamed a “quarterback whisperer,” he is now retired from fulltime coaching (although still a front-office consultant for Tampa Bay), and did a round of media interviews for Novartis, including one with People and Forbes.

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Amy West, Novo Nordisk head of US digital innovation and transformation (Illustration: Assistant Editor Kathy Wong for Endpoints News)

Q&A: No­vo Nordisk dig­i­tal in­no­va­tion chief Amy West dis­cuss­es phar­ma pain points and a health­care 'easy but­ton’

Amy West joined Novo Nordisk more than a decade ago to oversee marketing strategies and campaigns for its US diabetes portfolio. However, her career path shifted into digital, and she hasn’t looked back. West went from leading Novo’s first digital health strategy in the US to now heading up digital innovation and transformation.

She’s currently leading the charge at Novo Nordisk to not only go beyond the pill with digital marketing and health tech, but also test, pilot and develop groundbreaking new strategies needed in today’s consumerized healthcare world.

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