- Danish drugmaker Novo Nordisk said Wednesday that one of its marketed diabetes medications seems to work in another widespread disease, a liver condition known as NASH.
- Tucked into Novo's newest earnings report were topline results from a mid-stage clinical trial that showed the drug, semaglutide, was better than placebo at resolving NASH, or nonalcholic steatohepatitis, without worsening its characteristic liver scarring. The study tested three doses of semaglutide over the course of 72 weeks and found that each was significantly more effective than placebo.
- With positive results in hand, Novo said it is now assessing the next clinical development steps for semaglutide in NASH. The drug secured U.S. approval in 2017 as an injectable treatment for Type 2 diabetes, after which it was sold under the brand name Ozempic. A pill form, marketed as Rybelsus, was approved in 2019.
Semaglutide is one member in a class of drugs called GLP-1 agonists, which regulate blood sugar levels by stimulating insulin production. While their effect has obvious applications to diabetes care, these drugs have also attracted much attention as potential treatments for NASH, a disease thought to affect millions of people in the U.S. alone.
Though there are currently no approved drugs for NASH, analysts at SVB Leerink wrote in a December report that treatment will likely involve combinations of drugs, with GLP-1s serving as a backbone on which to build those combinations.
The analysts also noted a "sense of excitement" around semaglutide for many of the top NASH doctors and researchers to whom they had spoken. As such, Novo's medicine had become "an early favorite among potential drugs in development for NASH," according to SVB Leerink.
The excitement, though, may be tempered by hurdles that lay ahead, as well as by more mixed data on a key secondary measure in Novo's study.
On the research end, it looks as though NASH can develop in multiple ways. That makes finding a drug that works for a wide variety of patients difficult, as shown by the fact that only one company, Intercept Pharmaceuticals, has been able achieve positive results in a late-stage NASH study. Even then, less than a quarter of patients given Intercept's drug achieved the study's main goal.
Should semaglutide ultimately gain approval in NASH, there would likely be commercial challenges as well. Insurers have felt burned by high-priced medicines for other liver diseases, and the expectation is they won't hesitate to push back against expensive NASH drugs, particularly if they offer only incremental benefits.
In Novo's case, the Phase 2 data released Wednesday show 59% of patients who received the highest of three semaglutide doses experienced NASH resolution without their liver fibrosis getting worse. In the medium and lower dose groups, 36% and 40% of patients hit that same endpoint, as did 17% of patients in the placebo arm.
Novo said safety data was consistent with what's been seen with semaglutide in other trials. The more common side effects from Ozempic include nausea, vomiting and diarrhea, while the drug's label also warns about the potential for serious side effects such as thyroid tumors.
Though Novo's drug hit on NASH resolution, analysts at SVB Leerink and Baird highlighted how it appears to have missed a crucial secondary endpoint in the trial, showing no statistically significant benefit in reducing fibrosis. Novo management did note, however, that there was a "trend" toward improvement among patients who received the highest drug dose, Leerink analyst Thomas Smith wrote in a note to clients.
While the Food and Drug Administration has signaled that NASH drugs could gain approval after showing positive effects on either NASH resolution or fibrosis, patients with the most severe forms of the disease typically need antifibrotic medications to avoid progressing toward cirrhosis.
Should Intercept's drug gain approval, the company plans on targeting the roughly half a million patients who it estimates have advanced fibrosis and are under specialist care.