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.

Steve Holtzman was awoken by a 1 a.m. call from a doctor at Duke University asking if he could put some pigs on a plane and fly them from Ohio to North Carolina that day. A motorcyclist had gotten into a horrific crash, the doctor explained. He believed the pigs’ livers, sutured onto the patient’s skin like an external filter, might be able to tide the young man over until a donor liver became available.

David Livingston, the Dana-Farber/Harvard Med scientist who helped shine a light on some of the key molecular drivers of breast and ovarian cancer, died unexpectedly last Sunday.

One of the senior leaders at Dana-Farber during his nearly half century of work there, Livingston was credited with shedding light on the genes that regulate cell growth, with insights into inherited BRCA1 and BRCA2 mutations that helped lay the scientific foundation for targeted therapies and earlier detection that have transformed the field.

Pfizer will present its case to the FDA’s vaccine adcomm next week, seeking authorization for a lower-dose version of its Covid-19 vaccine for kids ages 5 through 12, which the Biden administration said will likely begin rolling out early next month.

Two primary doses of the 10 µg vaccine (the dose for those ages 12 and up is 30 μg) given 3 weeks apart in this group of children “have shown a favorable safety and tolerability profile, robust immune responses against all variants of concern including Delta, and vaccine efficacy of 90.7% against laboratory-confirmed symptomatic COVID-19,” the company said in briefing documents ahead of next Tuesday’s meeting of the FDA’s Vaccines and Related Biological Products Advisory Committee.