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.”

A new era of treat­ment: How bio­mark­ers are chang­ing the way we think about can­cer

AJ Patel was recovering from a complicated brain surgery when his oncologist burst into the hospital room yelling, “I’ve got some really great news for you!”

For two years, Patel had been going from doctor to doctor trying to diagnose his wheezing, only to be dealt the devastating news that he had stage IV lung cancer and only six months to live. And then they found the brain tumors.

“What are you talking about?” Patel asked. He had never seen an oncologist so happy.

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ProFound Therapeutics founding team

Flag­ship's lat­est biotech could turn some of the thou­sands of new pro­teins it dis­cov­ered in­to ther­a­pies — and it has $75M to start

Flagship Pioneering, the incubator of Moderna and dozens of other biotechs, says it has landed upon tens of thousands of previously undiscovered human proteins. The VC shop wants to potentially turn them into therapeutics.

Like other drug developers that have turned proteins into therapeutics (think insulin for diabetes), Flagship’s latest creation, ProFound Therapeutics, wants to tap into this new trove of proteins as part of its mission to treat indications ranging from rare diseases to cancer to immunological diseases.

Richard Silverman, Akava Therapeutics founder and Northwestern professor

This time around, Lyri­ca's in­ven­tor is de­vel­op­ing his North­west­ern dis­cov­er­ies at his own biotech

Richard Silverman was left in the dark for the last five years of clinical development of the drug he discovered. The Northwestern University professor found out about the first approval of Lyrica, in the last few days of 2004, like most other people: in the newspaper.

What became one of Pfizer’s top-selling meds, at $5 billion in 2017 global sales before losing patent protection in 2019, started slipping out of his hands when Northwestern licensed it out to Parke-Davis, one of two biotechs that showed interest in developing the drug in the pre-email days, when the university’s two-person tech transfer team had to ship out letters to garner industry appetite.

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Michael Corbo, Pfizer CDO of inflammation & immunology

UP­DAT­ED: Plan­ning ahead for crowd­ed ul­cer­a­tive col­i­tis mar­ket, Pfiz­er spells out PhI­II da­ta on $6.7B Are­na drug

Pfizer has laid out the detailed results behind its boast that etrasimod — the S1P receptor modulator at the center of its $6.7 billion buyout of Arena Pharma — is the winner of the class, potentially leapfrogging an earlier entrant from Bristol Myers Squibb.

Pivotal data from the ELEVATE program in ulcerative colitis — which consists of two Phase III trials, one lasting 52 weeks and the other just 12 weeks — illustrate an “encouraging balance of efficacy and safety,” according to Michael Corbo, chief development officer of inflammation & immunology at Pfizer. The company is presenting the results as a late breaker at Digestive Disease Week.

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David Ricks, Eli Lilly CEO (David Paul Morris/Bloomberg via Getty Images)

Eli Lil­ly set to in­vest $2.1B in home state man­u­fac­tur­ing boost

Eli Lilly is looking to expand its footprint in its home Hoosier State by making a major investment in manufacturing.

The pharma is investing $2.1 billion in two new manufacturing sites at Indiana’s LEAP Lebanon Innovation and Research District in Boone County, northwest of Lilly’s headquarters in Indianapolis.

The two new facilities will expand Lilly’s manufacturing network for active ingredients and new therapeutic modalities, including genetic medicines, according to a press release.

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Up­dat­ed: US sees spike in Paxlovid us­age as Mer­ck­'s mol­nupi­ravir and As­traZeneca's Evusheld are slow­er off the shelf

New data from HHS show that more than 162,000 courses of Pfizer’s Covid-19 antiviral Paxlovid were administered across the US over the past week, continuing a streak of increased usage of the pill, and signaling not only rising case numbers but more awareness of how to access it.

In comparison to this week, about 670,000 courses of the Pfizer pill have been administered across the first five months since Paxlovid has been on the US market, averaging about 33,000 courses administered per week in that time.

Almirall is tapping artificial intelligence on behalf of its sales force for insights and efficiencies. (via Shutterstock)

Almi­rall rolls out sales rep ar­ti­fi­cial in­tel­li­gence sys­tem, cut­ting pre-call prep and 'wind­shield time'

Dermatology specialty pharma Almirall is making its sales reps smarter. Not with extra training or educational courses, but instead with artificial intelligence tools.

It began a soft launch of a sales rep AI and machine learning platform it calls Polaris last August in one of its 7 US coverage regions. The platform from Aktana gathers information from across Almirall internal sources and external ones – such as claims and prescribing data – to generate insights for reps. Now, instead of spending hours prepping for a sales call, Polaris can generate details about a physician’s preferences, past behaviors and prescription habits for reps in minutes, said Almirall head of commercial operations Vincent Cerio.

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Pfiz­er and CD­MOs ramp up Paxlovid man­u­fac­tur­ing with Kala­ma­zoo plant ex­pan­sion lead­ing the way

As the Covid-19 pandemic continues to evolve, pharma companies and manufacturers are exploring how to step up production on antivirals.

Pfizer is planning to expand its Kalamazoo-area facility to increase manufacturing capabilities for the oral Covid-19 antiviral Paxlovid, according to a report from Michigan-based news site MLive. The expansion of the facility, which serves as Pfizer’s largest manufacturing location, is expected to create hundreds of “high-skilled” STEM jobs, MLive reported. No details about the project’s cost and timeline have been released, but according to MLive, Pfizer will announce the details of the expansion at some point in early June.

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FDA spells out the rules and re­stric­tions for states seek­ing to im­port drugs from Cana­da

The FDA is offering more of an explanation of the guardrails around its program that may soon allow states to import prescription drugs in some select circumstances from Canada, but only if such imports will result in significant cost reductions for consumers.

While the agency has yet to sign off on any of the 5 state plans in the works so far, and PhRMA’s suit to block the Trump-era rule allowing such imports is stalled, the new Q&A guidance spells out the various restrictions that states will have to abide by, potentially signaling that a state approval is coming.