- Gilead Sciences and Novo Nordisk announced Friday a collaboration in non-alcoholic steatohepatitis, or NASH. Gilead will contribute two Phase 2 projects to combine with Novo's semaglutide, which is approved in an injectable form as Ozempic and is under review as an oral formulation.
- The announcement comes a day after Gilead revealed early Phase 2 data for a combination of its two experimental drugs that showed promising signs of liver fat and enzyme reductions.
- The two companies are trying to play catch-up to Intercept Pharmaceuticals, which appears poised to win approval of Ocaliva as the first drug specifically targeting NASH.
Intercept has established a big lead in developing a treatment for a medically underserved NASH field. This is a condition in which an accumulation of fat in the liver leads to fibrosis and, eventually, cirrhosis, and is believed to be growing in prevalence thanks to rising obesity rates in Western countries.
However, Intercept's drug, Ocaliva (obeticholic acid), comes with potentially troublesome levels of side effects, most notably cholesterol elevations and itching that requires additional clinical management. This has encouraged competitors to try to at least match Ocaliva on effectiveness and beat it on side effect profile.
Gilead was seen as a close competitor to Intercept, but those hopes took a hit when the biotech's lead NASH drug selonsertib failed to improve fibrosis in a Phase 3 trial — a major clinical misstep.
Fortunately, the California-based biotech had some projects on the bench, including cilofexor and firsocostat, which had early Phase 2 data on liver fat and enzymes at the European Association for the Study of the Liver (EASL) congress in Vienna, Austria. Cilofexor is a farnesoid X receptor (FXR) agonist and fisocostat is an acetyl-CoA carboxylase (ACC) inhibitor.
"The takeaway from EASL so far is some drugs [like Ocaliva] will work but ultimately various combinations could emerge down the road to further improve efficacy," Jefferies analyst Michael Yee wrote in a note to clients.
Novo has been nibbling at the edges of NASH science for some time. Liraglutide, the active ingredient in the injectable diabetes drug Victoza, has been shown to perform significantly better than placebo in achieving NASH resolution and arresting fibrosis progression in a small trial.
Semaglutide is a similar GLP-1 agonist agent that has a longer half life and has proven suitable for oral dosing, and thus makes a better potential candidate to join Gilead's combination.
"The mechanism of action of both FXR (bile acid metabolism) and ACC (fatty acid metabolism) are different to those observed with semaglutide in preclinical models," Marcus Schindler, Novo's senior vice president for global drug discovery, wrote to BioPharma Dive in an email.
"Therefore, it is expected that the mechanisms will offer complementary effects when combined and deliver a better efficacy profile for the patients with NASH."
Analysts added that the collaboration suggests Gilead may not turn to acquisitions to beef up its NASH pipeline in the wake of the selonsertib setback.
Both Gilead and Novo are companies in need of some good news in the clinical development department. Gilead's waning hepatitis C franchise left a big hole to be filled, and the company has stumbled when venturing outside its usual core antiviral business.
Novo's strength has been in diabetes and metabolic medicine, increasingly challenging and expensive areas. The Danish drugmaker is further limited by a decision more than 10 years ago to exit small-molecule drug development and focus on protein-based therapies, restricting the types of disorders it can treat.