- Allergan plc's drug cenicriviroc (CVC) never met the primary endpoint of a mid-stage study testing it as a treatment for nonalcoholic steatohepatitis (NASH). It did, however, show some benefit for improving fibrosis. On Friday, the drugmaker unveiled new follow-on data reinforcing that benefit.
- The design of the CENTAUR study put half of the participants on cenicriviroc and half on placebo. After one year, the experimental arm continued receiving the drug while the control arm split in two, with one piece switching to cenicriviroc. After a second year of treatment, 20% patients who switched experienced fibrosis reduction by at least one stage and no NASH worsening, whereas 13% of the patients remaining on placebo had similar outcomes.
- Allergan is currently recruiting patients for the Phase 3 AURORA investigation, a placebo-controlled trial that will evaluate the drug's safety and efficacy as a treatment for liver fibrosis in adults with NASH.
Allergan did a deep dive into NASH candidates last year with its $1.7 billion acquisition of Tobira Therapeutics Inc. and $50 million takeover of privately held Akarna Therapeutics. At the time, the Dublin-based drugmaker expected the NASH market would grow as large as $8 billion annually and treat roughly 5 million patients.
The Tobira deal was especially important to any dreams Allergan had for securing its spot at the top of the space, as it provided the company with two investigational therapies, CVC and evogliptin.
CVC, however, had failed the CENTAUR study just two months before it came under Allergan's control. Tobira tried to spin the negative readout, in which CVC didn't improve inflammation or liver cell damage in NASH patients, by touting the drug's efficacy in reducing fibrosis.
Following an end-of-Phase 2 meeting with the Food and Drug Administration — wherein the agency agreed to a Phase 3 study provided the primary endpoint was fibrosis reduction — Allergan announced plans to do just that and initiate late-stage testing in mid-2017.
The follow-on data from CENTAUR now reinforces that decision. While patients who switched from placebo to CVC did show fibrosis benefit, Evercore ISI analyst Umer Raffat noted during a Sept. 22 webcast that Allergan didn't release the p-value — which determines statistical significance — for that outcome.
"This was a failed study, we have to acknowledge that," EvercoreISI analyst Umer Raffat said during the webcast.
Perhaps underscoring the mixed results, patients who started and remained on CVC treatment over two years showed no significant difference in fibrosis reduction by at least one stage with no worsening of NASH versus those taking placebo, according to the new data from Allergan.
"Would you really expect a dramatic turnaround at two years?" Raffat said.
Importantly, Allergan has a deal with Novartis AG pairing CVC with the Swiss pharma's LJN452 in a Phase 2 study for NASH, and that's where investors should be paying attention, according to Raffat.
"The whole idea was to do combinations, so you have to think of this drug [in combination]," he said.
"These data confirm the safety profile and anti-fibrotic effect of CVC after one year of treatment. Allergan is committed to advancing our portfolio of NASH treatment programs," the company's head of R&D, David Nicholson, said in a Sept. 22 statement. "We have gained important insights from this analysis which will further support our progress with CVC. The CENTAUR trial is a first of its kind with three biopsies in patients with NASH disease and liver fibrosis."
Allergan shares were up a little more than 1% to $204.95 apiece in mid-morning trading on Friday.