- On Friday, Gilead Sciences highlighted clinical data showing one of its candidates offered benefits across multiple liver diseases. Analysts, however, remain unconvinced the drug can stack up to rival therapies that work in a similar way.
- GS-9674 scored positive results in separate Phase 2 trials evaluating it as a treatment for advanced fibrosis due to nonalcoholic steatohepatitis (NASH) and primary sclerosing cholangitis (PSC). In the NASH study, around 30% of patients taking a high dose of the drug once daily for 24 weeks experienced at least a 30% reduction in liver fat, after correcting for placebo. And in the PSC study, patients on that same high dose had significant reductions in several liver enzyme levels after 12 weeks compared to placebo.
- Gilead's drug promotes a protein called farnesoid X receptor (FXR), which impairs bile acid synthesis. Intercept Pharmaceuticals has its own FXR agonist on the market, Ocaliva (obeticholic acid), for primary biliary cirrhosis (PBC), while a handful of others are in clinical testing. Novartis' tropifexor is one in particular that poses a competitive threat to GS-9674, according to analysts.
Though there remain unmet medical needs in PSC and PBC, the prized target among liver drugmakers in recent years has been NASH. The disease is thought to affect about 30 million Americans, a patient population that both large pharmas and smaller biotechs are keen to tap into.
Much of the attention surrounding GS-9674 has therefore been on its applications in NASH. Gilead is testing the drug in that indication as a monotherapy and in combination with GS-0976, an oral Acetyl-CoA carboxylase (ACC) inhibitor, and/or selonsertib, an apoptosis signal-regulating kinase 1 (ASK) inhibitor. A Phase 2 study of those combinations is expected to wrap up late next year.
Gilead executives are bullish on the data presented thus far. Speaking with BioPharma Dive, Rob Myers, the company's vice president of liver diseases clinical research, said Phase 2 results support pushing the drug into late-stage trials for NASH and PSC.
Analysts, however, have different takeaways.
After the American Association for the Study of Liver Diseases released abstracts ahead of its annual meeting, Raymond James analyst Steven Seedhouse concluded, "At a minimum, the data suggest [Intercept's] Ocaliva is almost certainly the better FXR agonist. In fact, the collective Phase 2 data ... suggest GS-9674 may not be worth pursuing further."
"We wouldn't be surprised if Gilead terminated the program at some point, pending outcome of the ongoing Phase 2 combination study," Seedhouse wrote.
He also explained in an investor note a couple weeks later the FXR agonist space has become increasingly crowded. On that front, he pointed out the reduction in gamma-glutamyl transferase and alanine aminotransferase (ALT), two liver enzymes, seen with GS-9674 treatments isn't as strong as that of Intercept's Ocaliva.
What's more, the Gilead drug isn't doing as well on itching rates as Novartis', which could be problematic for a disease like NASH that is largely asymptomatic.
"I think it's a dangerous business to compare, for example, changes in ALT across different studies and different patient populations at different time points," Gilead's Myers said in an interview, highlighting also that just one patient in the GS-9674 NASH discontinued due to itching.
"We know that, although ALT can be helpful if you see changes, it's correlation with histology is actually not fantastic," he added. "Really, I think to differentiate these molecules in the end, we're gonna need to see studies that include liver histology."
Meanwhile, Jefferies has talked with an expert in the field who the investment bank noted is "increasingly warming up to [Ocaliva] based on various new competitor datasets."
To that point, the expert was "slightly less positive" on Gilead's drug due to a more transient efficacy compared to Intercept's.