Novartis | Tropifexor and licogliflozin

Novartis headquarters
Novartis has two NASH prospects in phase 2: SGLT1/2 inhibitor licogliflozin and FXR agonist tropifexor. (Novartis)

Company: Novartis 
Drug names: Tropifexor and licogliflozin 
Mechanisms: FXR agonist and SGLT1/2 inhibitor 
Stage: Phase 2 and phase 2a 
Next steps: Testing both prospects in combination with drugs that work through different mechanisms to figure out where each will fit in the treatment of NASH 

Novartis reported 12-week data for two NASH prospects at this year’s meeting of the American Association for the Study of Liver Diseases (AASLD). The first, tropifexor, is one of a crowd of FXR agonists that may turn out to be better than Intercept’s obeticholic acid (OCA). The second, licogliflozin, is an SGLT1/2 inhibitor, a mechanism familiar to diabetes that could make a dent in NASH. It works by blocking the absorption of glucose in the gut and reabsorption of glucose from the kidney. 

Like Intercept’s OCA and Gilead’s cilofexor, tropifexor works by modulating FXR, a nuclear receptor that regulates bile acid levels in the liver. Earlier data showed that lower doses of tropifexor, 60 μg and 90 μg, tamped down inflammation and fat buildup in the liver. The data presented at AASLD showed that higher doses, 140 μg and 200 μg, had “robust and dose-dependent decreases” in liver enzyme levels, body weight and liver fat after 12 weeks, researchers said. Like other FXR agonists, tropifexor patients also saw “mild pruritis,” or skin itching, and “minor dose-related" increases in LDL, or “bad,” cholesterol. 

Novartis expects to complete the study in April 2020, according to ClinicalTrials.gov. The effect of the drug on NASH as measured by liver biopsy, along with trials of tropifexor in combination with other drugs that work differently, will “define future therapeutic options in fibrotic NASH,” the investigators wrote in the study. 

As for licogliflozin, the phase 2a study compared two doses of the drug to placebo in 110 patients with NASH. After 12 weeks of treatment, patients on both doses—30 mg and 150 mg—saw their liver enzyme levels, liver fat and body weight decrease, with patients on the higher dose doing better on each metric. 

“Studies of longer duration and in combination with drugs that have different mechanisms of action are needed to define the role of licogliflozin as a therapeutic option for NASH,” the researchers wrote.

Novartis | Tropifexor and licogliflozin

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