Shire’s fast-track NASH drug abruptly stopped in phase 2

Shire has quietly cut the trial of an FDA fast-tracked fatty liver disease drug, although it’s not giving much away about what happened.

Buried within its second-quarter financials this morning, Shire said it was curtains for SHP626 (volixibat), its phase 2 experimental drug for steatohepatitis (NASH) with liver fibrosis.

It was being worked as a once-a-day, oral inhibitor of the apical sodium dependent bile acid transporter (ASBT), a protein which is primarily responsible for recycling bile acids from the intestine to the liver.

There’s not much to go on from Shire, accept to say that: "In June 2018, Shire announced that the phase 2 clinical study of SHP626 has been discontinued. Shire is evaluating other options for the program."

Shire has previously noted that "The most common adverse events occurring in phase 1 trials of SHP626 were gastrointestinal in nature, predominantly diarrhea. While this occurred in most patients, it was not considered serious. There was one serious adverse event reported that was considered related to SHP626, alanine aminotransferase elevation, that led to discontinuation of drug."

Almost exactly two years ago, the biopharma was given an FDA fast track for the drug, which can help speed up its pathway to approval, based on the phase 1 as well as preclinical data.

Its phase 2 for SHP626 was a randomized, placebo-controlled, double-blind study to seek out safety, tolerability and efficacy of three doses of volixibat over 48 weeks in adult patients with NASH. The test was carried out in the U.S., Canada and the U.K.

NASH is set to be a multibillion-dollar market with a number of biopharmas, including Shire, Bristol-Myers Squibb, GenFit, Intercept and others trying to break into this therapy area.

Many have suffered setbacks in these efforts, however, with a number of different MOAs being used to try and attack the fatty buildup that can occur in the liver in obese patients, which can in turn lead to scarring and potentially liver disease and failure.

The drug was originally licensed from Lumena Pharmaceuticals. This is the second drug to hit trouble from that deal, with Shire’s other liver drug, SHP625, also beset with issues.

Back in 2016, the phase 2 "Cameo" trial, a 14-week study in patients with primary sclerosing cholangitis (PSC), an uncommon chronic liver disease, missed its secondary endpoints.

That came exactly a year after Shire posted data from SHP625 (formerly known as LUM001) that showed it missed all of its objectives in the phase 2 Imago study involving 20 children with the genetic disease Alagille syndrome (ALGS).

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