Just a month be­fore hand­ing In­ter­cept Phar­ma­ceu­ti­cals a CRL for Ocali­va in NASH, the FDA be­gan eval­u­at­ing the drug for a po­ten­tial risk of liv­er dis­or­der in pri­ma­ry bil­iary cholan­gi­tis (PBC) pa­tients. The probe, which launched in May, was dis­closed by the com­pa­ny deep down in their lat­est quar­ter­ly re­port filed with the SEC, and had not oth­er­wise been com­mu­ni­cat­ed pub­licly by In­ter­cept un­til re­ports sur­faced this week.

The FDA has no­ti­fied us that in the course of its rou­tine safe­ty sur­veil­lance, in May 2020 the FDA be­gan to eval­u­ate a new­ly iden­ti­fied safe­ty sig­nal re­gard­ing liv­er dis­or­der for Ocali­va which the FDA clas­si­fied as a po­ten­tial risk.

Ocali­va was ap­proved in 2016 to treat PBC, a chron­ic dis­ease that af­fects the liv­er’s bile ducts. In­ter­cept spokesman Christo­pher Frates said the biotech is work­ing with the FDA on what will like­ly be a 12-month eval­u­a­tion.

An FDA spokesper­son de­clined to of­fer any ad­di­tion­al in­for­ma­tion aside from what was post­ed in FAERS, the agency’s ad­verse event re­port­ing sys­tem, which states they are “eval­u­at­ing the need for reg­u­la­to­ry ac­tion.”

The probe is the lat­est blow to In­ter­cept in the last few months. In June, the FDA re­ject­ed its NDA for obeti­cholic acid, the ac­tive in­gre­di­ent in Ocali­va, for the treat­ment of NASH. In­ter­cept said reg­u­la­tors want­ed longer term da­ta from their Phase III tri­al to back the sur­ro­gate end­point, re­duc­tion in liv­er fi­bro­sis. Com­pa­ny ex­ec­u­tives ar­gued then that they were blind­sided.

CEO Mark Pruzan­s­ki had said in a state­ment:

At no point dur­ing the re­view did the FDA com­mu­ni­cate that OCA was not ap­prov­able on an ac­cel­er­at­ed ba­sis, and we strong­ly be­lieve that the to­tal­i­ty of da­ta sub­mit­ted to date both meet the re­quire­ments of the Agency’s own guid­ance and clear­ly sup­port the pos­i­tive ben­e­fit-risk pro­file of OCA.

In a Sep­tem­ber SEC fil­ing, In­ter­cept an­nounced that 170 jobs were on the chop­ping block, equal to rough­ly 25% of its staff, in or­der to save cash for its con­tin­ued pur­suit of NASH ap­proval. In­ter­cept shares were down 8% yes­ter­day when news of the FDA probe be­came wide­ly known. An in­vestor on Twit­ter first no­ticed the buried dis­clo­sure.

Back in 2018, the FDA slapped Ocali­va with a black box warn­ing, due to the drug be­ing “in­cor­rect­ly dosed” dai­ly in­stead of week­ly. “To en­sure cor­rect dos­ing and re­duce the risk of liv­er prob­lems, we are clar­i­fy­ing the cur­rent rec­om­men­da­tions for screen­ing, dos­ing, mon­i­tor­ing, and man­ag­ing PBC pa­tients with mod­er­ate to se­vere liv­er dis­ease tak­ing Ocali­va,” it an­nounced.

A little less than two years after completing its $42 million Series B round, InCarda has returned to the venture well.

The San Francisco-based biotech announced the first portion of its Series C on Wednesday, pulling in $30 million in new funding. Most of the money will give enough runway for InCarda’s InRhythm program, an inhaled therapeutic aiming to treat sudden episodes of irregular heartbeats, through its Phase II trials and prepare it for Phase III.

Prothena’s prasinezumab may not have met the primary endpoint in Phase II, but its partners at Roche are seeing enough to move it into a late-stage trial for Parkinson’s disease.

The Phase IIb will build on the Phase II PASADENA study, adding a subgroup of early Parkinson’s patients on stable levodopa therapy to the population.

It’s a significant milestone for a $600 million deal that dates back to 2013, as dosing of the first patient — expected next year — will trigger a $60 million milestone payment to Prothena.

CARB-X, a global partnership looking to spur the development of new antibacterial drugs, is awarding Cellics Therapeutics $3.94 million to do what president and CMO Steve Chen calls “looking at traditional drug development upside down.”

Instead of going after a target directly — in this case bacterial toxins and inflammatory cytokines that cause sepsis — Cellics researchers “flip it around” to examine the host cells being attacked. The UC San Diego spinout then creates what it calls “nanosponges” — nanoparticles cloaked in the fragments of macrophage cell membranes. Chen says the “sponges” are designed to trap the sepsis-causing endotoxins and cytokines on their cell membranes, neutralizing them.