Novartis and Allergan have agreed to carry out a Phase IIb study combining one of Novartis’ farnesoid X receptor (FXR) agonist candidates with Allergan’s late-stage C-C chemokine receptor types 2 and 5 (CCR2/5) blocker cenicriviroc (CVC) for treating nonalcoholic steatohepatitis (NASH). No financial details of the deal were disclosed.
“Our clinical collaboration with Allergan expands our development programs for NASH, bringing together science and expertise to investigate a potential new combination therapy in an effort to make a positive change for people living with this condition,” said Vas Narasimhan, M.D., global head, drug development, and CMO at Novartis. “We believe that collaboration is key to developing the best possible treatments that are urgently needed for NASH patients.”
CVC is a once-daily, Phase III-ready oral immunomodulator, which Allergan acquired through its $1.695 billion acquisition of NASH therapeutics specialist Tobira in September 2016. A previous Phase IIb study, CENTAUR, showed that CVC treatment led to clinically meaningful improvements in fibrosis of at least one stage, without worsening NASH after 1 year of treatment. Allergan says this is one of only two approvable Phase III NASH study endpoints. CVC has been granted fast track designation by the FDA for the NASH and liver fibrosis indications. Allergan’s acquisition of Tobira also gave it the oral dipeptidyl peptidase-4 (DPP-4) inhibitor evogliptin, which is undergoing Phase I safety, tolerability, and pharmacokinetic testing alone and in combination with CVC.
Within 24 hours of its Tobira acquisition, Allergan announced it was buying another NASH therapeutics firm, Akarna, for $50 million upfront, to acquire a complementary preclinical-stage FXR agonist pipeline, including lead compound AKN-083.
Novartis is developing its FXR agonist program for treating chronic liver diseases, including NASH. The most advanced, non-bile acid FXR agonist candidate is in Phase II development and has also been granted fast track designation by the U.S. regulator for the NASH liver cirrhosis indication.
In December, Novartis and Conatus Pharmaceuticals inked a $50 million up-front global option, collaboration, and license agreement to develop the latter’s oral pan-caspase inhibitor emricasan for NASH fibrosis and cirrhosis. At the time, Novartis said emricasan may also be cominbed with its own FXR agonists.