FDA lifts hold on CymaBay’s NASH drug, but the com­pa­ny may still leave the ail­ing field

Eight months af­ter a sin­gle tri­al read­out blew up their NASH pro­gram, their stock price and put de­vel­op­ment around their lead com­pound on in­def­i­nite hold, CymaBay has been cleared to get back to work.

The FDA has lift­ed the clin­i­cal hold it placed on the com­pa­ny and their ex­per­i­men­tal se­ladel­par last year af­ter planned biop­sies for their NASH tri­al re­vealed “atyp­i­cal his­to­log­i­cal find­ings” — a phrase that here means the drug, rather than re­duc­ing pa­tients’ liv­er fat, ap­peared to lead to liv­er dam­age. The Phase IIb tri­al was ter­mi­nat­ed, along with a Phase IIa for pri­ma­ry scle­ros­ing cholan­gi­tis (PSC). Stud­ies on pri­ma­ry bil­iary cholan­gi­tis were put on hold. SVB Leerink called it “a worst case sce­nario” and the stock fell from $5.55 to $1.89.

CymaBay said that an ex­pert pan­el they con­vened af­ter the tri­al read­out found “no clin­i­cal, bio­chem­i­cal, or his­to­log­i­cal ev­i­dence” that se­ladel­par was in­jur­ing pa­tients and “unan­i­mous­ly sup­port­ed” re-ini­ti­at­ing the tri­als. The FDA lift­ing the hold al­lows the com­pa­ny to pro­ceed with 3 tri­als test­ing the drug in NASH, pri­ma­ry bil­iary cholan­gi­tis and pri­ma­ry scle­ros­ing cholan­gi­tis.

Su­jal Shah

It doesn’t ap­pear that they will pro­ceed with all of them, though. Even if the drug wasn’t harm­ing NASH pa­tients in that tri­al, the com­pa­ny is still left with the fact that the drug didn’t ap­pear to be help­ing ei­ther. CymaBay didn’t say they were aban­don­ing NASH, but the in­di­ca­tion — a po­ten­tial block­buster mar­ket that once float­ed CymaBay’s stock – was con­spic­u­ous­ly ab­sent from CEO Su­jal Shah’s re­marks.

“This is a piv­otal event for se­ladel­par, which had gar­nered a high de­gree of pa­tient in­ter­est based on its promis­ing po­ten­tial for an­ti-cholesta­t­ic, an­ti-in­flam­ma­to­ry and re­duced symp­tom bur­den in pa­tients with PBC,” he said. “We are grat­i­fied and en­er­gized to be able to once again ad­vance se­ladel­par in­to a reg­is­tra­tional pro­gram to con­firm its ben­e­fit. It is our un­wa­ver­ing goal to one day make it avail­able to pa­tients with PBC, and po­ten­tial­ly for oth­er chron­ic, in­flam­ma­to­ry liv­er dis­eases.”

CymaBay’s stock rose 32% on the news, from $3.51 to $4.66.

SVB Leerink’s Thomas Smith said the de­ci­sion to start with PBC was no sur­prise, giv­en they’ve al­ready gen­er­at­ed blind­ed Phase III da­ta and the fact that the re­main­ing clin­i­cal work for PBC like­ly re­quires fol­low­ing sev­er­al hun­dred pa­tients for a year, as op­posed to thou­sands of pa­tients over mul­ti­ple years for NASH.

“Im­por­tant­ly, this reg­u­la­to­ry up­date re­moves a key reg­u­la­to­ry over­hang, and should al­le­vi­ate some in­vestor con­cerns re­gard­ing both the tim­ing and na­ture of the FDA’s re­sponse to the in­de­pen­dent pan­el find­ings,” he wrote in a note to in­vestors. “This is a crit­i­cal step for­ward in re­sum­ing se­ladel­par clin­i­cal de­vel­op­ment, and we ex­pect strength in CBAY shares this morn­ing.”

Pri­or to the hold, CymaBay had been run­ning a Phase III tri­al in PBC, a chron­ic dis­ease that slow­ly de­stroys bile ducts in the liv­er. That tri­al will now pro­ceed. A Phase II tri­al read­out last year showed 5 mg and 10 mg dos­es of the drug led to a 36% and 43% re­duc­tion in al­ka­line phos­phatase, a chem­i­cal bio­mark­er for the dis­ease.

In an email, Shah said that al­though they’re be­gin­ning with PBC, the com­pa­ny con­tin­ues to see po­ten­tial in NASH. “NASH is a com­plex, het­ero­ge­neous dis­ease and while we are en­cour­aged by the ef­fects of se­ladel­par in NASH, par­tic­u­lar­ly on fi­bro­sis, there is more work to be done around the right de­vel­op­ment strat­e­gy (e.g. com­bi­na­tions) that should be ex­plored,” he said.

As re­cent­ly as the win­ter of 2019, the field was con­sid­ered to be one of the next block­buster mar­kets for phar­ma, but a se­ries of big tri­al fail­ures, in­clud­ing CymaBay’s, have crip­pled ex­pec­ta­tions. Gen­fit, once one of the lead­ing NASH biotechs, an­nounced yes­ter­day they were ter­mi­nat­ing the pro­gram af­ter a Phase III fail­ure.

M&A: a crit­i­cal dri­ver for sus­tain­able top-line growth in health­care

2021 saw a record $600B in healthcare M&A activity. In 2022, there is an anticipated slowdown in activity, however, M&A prospects remain strong in the medium to long-term. What are future growth drivers for the healthcare sector? Where might we see innovations that drive M&A? RBC’s Andrew Callaway, Global Head, Healthcare Investment Banking discusses with Vito Sperduto, Global Co-Head, M&A.

15 LGBTQ lead­ers in bio­phar­ma; Paul Stof­fels’ Gala­pa­gos re­vamp; As­traZeneca catch­es up in AT­TR; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

A return to in-person conferences also marks a return to on-the-ground reporting. My colleagues Beth Synder Bulik and Nicole DeFeudis were on-site at Cannes Lions, bringing live coverage of pharma’s presence at the ad festival — accompanied by photos from Clara Bui, our virtual producer, that bring you right to the scene. You can find a recap (and links to all the stories) below.

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Abortion-rights protesters regroup and protest following Supreme Court's decision to overturn Roe v. Wade. (AP Photo/Gemunu Amarasinghe)

Fol­low­ing SCO­TUS de­ci­sion to over­turn abor­tion pro­tec­tions, AG Gar­land says states can't ban the abor­tion pill

Following the Supreme Court’s historic decision on Friday to overturn Americans’ constitutional right to an abortion after almost 50 years, Attorney General Merrick Garland sought to somewhat reassure women that states will not be able to ban the prescription drug sometimes used for abortions.

Following the decision, the New England Journal of Medicine also published an editorial strongly condemning the reversal, saying it “serves American families poorly, putting their health, safety, finances, and futures at risk.”

AstraZeneca's new Evusheld direct to consumer campaign aims to reach more immunocompromised patients.

As­traZeneca de­buts first con­sumer cam­paign for its Covid-19 pro­phy­lac­tic Evusheld — and a first for EUA drugs

AstraZeneca’s first consumer ad for Evusheld is also a first for drugs that have been granted emergency use authorizations during the pandemic.

The first DTC ad for a medicine under emergency approval, the Evusheld campaign launching this week aims to raise awareness among immunocompromised patients — and spur more use.

Evusheld nabbed emergency authorization in December, however, despite millions of immunocompromised people looking for a solution and now more widespread availability of the drug.

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GSK says its drug for chron­ic hep B could ‘lead to a func­tion­al cure’ — but will it be alone or in com­bi­na­tion?

GSK, newly branded and soon-to-be demerged, shared interim results from its Phase II trial on its chronic hepatitis B treatment, one that it says has the “potential to lead to a functional cure.”

At a presentation at the EASL International Liver Congress, GSK shared that in around 450 patients who received its hep B drug bepirovirsen for 24 weeks, just under 30% had hepatitis B surface antigen and viral DNA levels that were too low to detect.

Joe Wiley, Amryt Pharma CEO

Am­ryt Phar­ma sub­mits a for­mal dis­pute res­o­lu­tion to the FDA over re­ject­ed skin dis­ease drug

The story of Amryt Pharma’s candidate for the genetic skin condition epidermolysis bullosa, or EB, will soon enter another chapter.

After the Irish drugmaker’s candidate, dubbed Oleogel-S10 and marketed as Filsuvez, was handed a CRL earlier this year, the company announced in a press release that it plans to submit a formal dispute resolution request for the company’s NDA for Oleogel-S10.

Sen. Thom Tillis (R-NC) (J. Scott Applewhite/AP Images)

Phar­ma-friend­ly sen­a­tor calls on FDA for a third time to show patent pro­tec­tions should­n't be blamed for high drug prices

North Carolina Republican Sen. Thom Tillis made a name for himself in the 2020 election cycle as the darling of the pharma industry, accepting hundreds of thousands in campaign contributions, even from the likes of Pfizer CEO Albert Bourla.

Those contributions have led Tillis to attempt to re-write patent laws in pharma’s favor, a move which failed to gain steam in 2019, and request for a third time since January that the FDA should help stop “the false narrative that patent protections are to blame for high drug prices.”

EMA signs off on 3 drugs re­cent­ly re­ject­ed by FDA, in­clud­ing Bio­Mar­in's new he­mo­phil­ia gene ther­a­py

The EMA’s human medicines committee on Friday recommended three new drugs for approval or conditional approval, even as their US counterparts have rejected these three for various reasons.

In a major move, CHMP offered a thumbs-up to a conditional marketing authorization for the first gene therapy to treat severe hemophilia A, although the agency cautioned that it’s so far unknown how long the effects of infusion will last.

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Sanofi, GSK tout 72% Omi­cron ef­fi­ca­cy in PhI­II tri­al of next-gen, bi­va­lent shot — with an eye to year-end roll­out

Sometimes, being late can give you an advantage.

That’s what Sanofi and GSK are trying to say as the Big Pharma partners report positive results from a late-stage trial of their next-gen bivalent Covid-19 vaccine, which was designed to protect against both the original strain of the SARS-CoV-2 virus and the Beta variant. Specifically, against Omicron, they note, the vaccine delivered 72% efficacy in all adults and 93.2% in those previously infected.