After halting Lumena buyout, Shire’s liver disease drug flunks again

Shire’s ($SHPG) liver drug SHP625 has flubbed another trial just months after the company ditched its $260 million-plus deal with Lumena Pharmaceuticals.

Buried in its Q1 results posted this morning, the drugmaker released data from its Phase II Cameo non-comparative open-label trial for SHP625--a 14-week study in patients with primary sclerosing cholangitis (PSC). 

PSC is an uncommon chronic liver disease in which the bile ducts inside and outside the liver progressively decrease in size due to inflammation and scarring, which can lead to liver failure.

Shire said that the primary objective of the study was to evaluate the safety and tolerability of SHP625--and that these “were consistent with previous SHP625 studies”.

There were also “significant reductions” from baseline in serum bile acids and pruritus by ItchRO score--the magnitude of the effect being consistent with what has been observed in SHP625 studies of other patient populations, according to the company, and the primary endpoints of the study. 

But there was no significant reduction from baseline in serum alkaline phosphatase or other liver parameters, meaning it missed its secondary endpoints. 

A Shire spokesperson said it was too early on in the trial program to make a final assessment: “We don’t yet know if the dose was optimal or if the timing was right to see effects on liver enzymes,” the spokesperson said. “We have seen encouraging effects on sBAs and liver enzymes in subsets of both the PFIC and ALGS population, so there is the potential for a greater effect with higher doses in the pediatric and potentially the adult populations. Much more analysis is needed and we are committed to assessing the totality of data in this program.”

This comes exactly a year after Shire posted data from SHP625 (formerly known as LUM001) showing that it missed all of its objectives in the Phase II Imago study involving 20 children with the genetic disease Alagille syndrome (ALGS).

Shire said today that it: “Continues to analyze the totality of the SHP625 data to determine an appropriate path forward.”

The drug candidate had been tipped by some analysts as a potential future blockbuster and was the most advanced asset acquired as part of Shire's $260 million-plus purchase of Lumena Pharmaceuticals in 2014.

But the Irish big biotech reported late last year that it reached a deal to terminate its buyout package for Lumena investors with a $90 million payoff. It is however still working on trials for the candidate.

In fact, SHP625 is also being tested in studies involving patients with primary biliary cirrhosis (which is also being pursued by several other biotechs and Big Pharma companies) and progressive familial intrahepatic cholestasis.

A follow-up compound called SHP626/LUM002--a drug with the same mechanism of action--began phase Ib trials in non-alcoholic steatohepatitis (NASH) last year--a condition that has Gilead ($GILD), Intercept Pharmaceuticals ($ICPT) and others chasing what some analysts believe could eventually be a $40 billion market.

- check out Shire’s results