Allergan injects Tobira candidate into Novartis NASH combo trial

Allergan has wasted little time in testing out its new fatty liver candidate that it got in the potentially $1.7 billion buyout of Tobira last year as it pens a new deal to wed cenicriviroc (CVC) to Novartis’ lead FXR agonist in a midstage test.

The pair will combine in a phase 2b safety and efficacy test in nonalcoholic steatohepatitis (NASH), aka fatty liver disease, a condition that affects millions of Americans but does not yet have a drug therapy on the market.

Allergan and Novartis are among a host of biopharmas, including Gilead, Intercept Pharmaceuticals, Genfit and Shire, all hoping to be the first to get an approval in what could be a major blockbuster market.

The FDA fast-tracked CVC is a once-daily, oral, phase 3-ready immunomodulator that blocks two chemokine receptors, CCR2 and CCR5, which are involved in inflammatory and fibrogenic pathways. Novartis’ med, meanwhile, is its farnesoid X receptor (FXR) agonist, which is also being used by several other companies in the race to market.

Allergan got hold of the drug late last year with its acquisition of Tobira, which could be worth up to $1.7 billion in biobucks. For its money, Allergan also got the phase 1 oral DPP-4 evogliptin, also targeting NASH.

But the drug has not had the best history: Back in July, before the buyout, Tobira fell by about half in premarket trading on news that its phase 2b trial to treat NASH using CVC failed to meet its primary endpoint.

The South San Francisco, CA-based company said it would push on, however, by shifting a secondary endpoint that it did meet in phase 2b into the new primary endpoint for phase 3, with a trial start slated for this year.

Novartis and Allergan hope a combined approach will boost efficacy in fatty liver disease patients and produce better results than CVC was getting on its own. Financial details of the deal were not made public.

“Our clinical collaboration with Novartis brings together our collective scientific and development expertise in NASH to focus on multi-therapy treatment, which is expected to be the most likely approach based on the multi-factorial aspects of this disease,” said David Nicholson, chief research and development officer at Allergan.

Allergan is working on AGN-242266 as well, which should enter the clinic this year, and also works as an FXR agonist that is “expected to be highly complementary to CVC and evogliptin.”

Novartis is also looking for other combos, and late last year gave Conatus a $50 million licensing/collaboration deal for its NASH med emricasan, a first-in-class, oral, pan-caspase inhibitor that is also set for phase 2b trials with Novartis’ FXR candidate. 

Analysts at Bernstein said the “deal partially validates Allergan’s acquisition of CVC,” and also “make us suspect NVS may have been the other bidder.”

It noted that CVC is positioned as a potential third entrant (around 2020) with a differentiated mechanism vs. the first two entrants, which are likely to come from Intercept and Genfit.  

“The profile of the drug in phase 2 was decent (not great) and assuming approval, Allergan will need to develop the market (certainly if Genfit and Intercept remain independent). We do not see this as an important commercial asset until at least 2024.”

It added that it sees sales for the NASH market at around $7 billion by 2025 if all goes to plan, although it says there are still many issues, such as creating less invasive disease markers and diagnosis (done now via liver biopsy), and measuring just how well these drugs work in the real world.