Interview – Overnight sensation Intercept settles down for hard yards

Ask Intercept Pharmaceuticals chief executive Mark Pruzanski whether he expected his company to become the poster child of the biotech bull market, and he will say it took him off guard.

“It took 12 years to have an overnight success,” Mr Pruzanski tells EP Vantage of the day his essentially one-product company quadrupled in value and became a market cap-peer of groups like Shire and Forest Laboratories. “We were absolutely caught by surprise.”

Intercept has in its hands what it and many observers believe might be an important advance in the treatment of the advanced liver diseases primary biliary cirrhosis (PBC) and non-alcoholic steatohepatitis (NASH). Its $5bn market value is largely based on the early cessation of the National Institutes of Health-led Flint trial because of a clear improvement of NASH symptoms (Boom! Trial halt turns Intercept into an improbable midcap company, January 10, 2014).

Mr Pruzanski says he believes the Flint findings came at a time when the hepatology field began to see that innovation in a previous area of focus had peaked.

“A lot of people think hep C has been solved,” he says. “NASH is the next tsunami. (The Flint findings) happened at exactly the right time.”

First in two decades

The product is obeticholic acid (OCA). The current treatment for PBC, ursodeoxycholic acid, known variously as UDCA or ursodiol, is a bile acid that displaces toxic concentrations of other bile acids, although its efficacy in preventing mortality or liver transplantation has been challenged.

OCA is an analogue that, like the natural bile acid chenodeoxycholic acid, is a ligand to the farnesoid X receptor. That receptor aids in bile acid homeostasis, and thus may protect the liver from the damage of bile accumulation in the liver once the ducts have been damaged.

The EASL International Liver Congress last week was an opportunity to present late breaking data from the Poise trial in PBC beyond the topline readout released last month. OCA in patients who were intolerant to ursodiol resulted in significant reductions in multiple liver enzyme measurements, with 46% reaching a primary endpoint of liver enzyme reductions, when compared to placebo.

Dropouts due to itchiness, itself a side effect of PBC, remain a concern – 7 patients of 73 (10%) in a group assigned to take 10mg OCA pills. Only one patient in 70 (1%) dropped out because of itchiness in a group that took 5mg for six months and then moved up to 10mg.

Neither the lead investigator, Frederik Nevens of the University of Leuven in Belgium, nor Intercept were shy about referring to Poise as the first phase III trial in PBC in two decades. It is no doubt because of this fact that Intercept believes the data on biochemical markers are sufficient to file for approval in the US and Europe by the end of 2014, which if accepted would put it on a timetable for approval sometime in 2015.

Intercept’s shares have slid 45% from their mid-March high, helped along by the biotech bubble’s deflation, some cardiovascular concerns and a fundraising earlier this month (Investors find it hard to see the good in Intercept as gloom triumphs, March 18, 2014).

Mr Pruzanski says he believes investors should take the fundraising as a sign of its commitment to building the company up sufficiently “to mount a robust international NASH programme.” The $183m fundraising is sufficient to fund the company through the end of 2016, providing sufficient funding to accelerate the NASH phase III studies and hire a commercial team.

In the PBC indication, he said he believes 30 sales representatives in US and Europe each would be sufficient to market to the hepatologists and gastroenterologists who typically would deal with this advanced group of patients. Significantly, it would provide useful pre-marketing for expanded approval.

“It’s the same group of prescribers who are seeing more NASH patients,” he says.

Bridging to NASH

As for NASH, the plan is to design a large trial aimed at showing OCA can improve outcomes. With interim analyses on surrogate endpoints being planned, the drug might be ready for regulatory review before those outcomes are measured. The acceptability of endpoints was certainly a concern when the Flint results were disclosed, as NASH currently has no pharmaceutical treatments – improving diet and exercise is the main intervention.

As NASH results from a buildup of fat in the liver, the belief is that growing prevalence of obesity will result in corresponding rise in NASH cases – thus Mr Pruzanski’s “tsunami” statement. Some analysts have put multi-billion dollar peak sales estimates in both NASH and PBC.

Getting to that first approval in PBC would be a significant de-risking event for NASH, and no doubt would improve the comfort of big pharma partners or buyers - provided those partners believe the opportunity is as significant as Intercept and its investors do. For all of Mr Pruzanski’s insistence about building a commercial force, a takeout cannot be far from his or his shareholders’ minds.

And if that were to happen based on success in upcoming catalysts, it would be worthy of a curtain call.

To contact the writer of this story email Jonathan Gardner in London at [email protected] or follow @JonEPVantage on Twitter