Mirum Pharmaceuticals is prepping for a new FDA approval application after its small molecule volixibat successfully alleviated itching in patients with a rare liver disease.
In 182 patients with primary sclerosing cholangitis (PSC), a chronic disease characterized by inflammation of the bile ducts that causes liver damage and an interminable full-body itch, those given twice-daily volixibat saw their itch severity reduced by 2.72 on an 11-point scale. This significantly topped the 1.08-point improvement in the placebo arm, Mirum announced May 4, hitting the phase 2 trial’s primary endpoint.
“We believe this is an outstanding treatment effect,” Mirum’s Chief Medical Officer Joanne Quan, M.D., said in a May 4 call with investors. “The magnitude of improvement is consistent with what we have observed in other cholestatic indications and reflects a meaningful benefit for patients.”
The Bay Area biotech has a meeting on the books with the FDA this summer to discuss a new drug application for volixibat, according to the release, with submission planned for the second half of the year.
Mirum’s stock jumped about 10% on the news, from $96.53 per share at Friday’s close to $105.20 at 10:00 a.m. ET on Monday.
Extreme itchiness, formally known as pruritus, is thought to occur in PSC because of compounds from liver bile that build up throughout the body. The itchiness can be so intense that it leads to suicidal thoughts, and constant scratching can cause sores and open wounds.
“Cholestatic pruritus is one of the most common symptoms in PSC, which remains a challenging disease to manage,” Kris Kowdley, M.D., director of Liver Institute Northwest and a professor at Washington State University, who was one of the trial’s investigators, said in the release. “In clinical practice, we have very limited options to effectively address this symptom. Results like these are encouraging, as they suggest the potential for a targeted approach that could represent a meaningful advance for PSC patients.”
Discontinuations in the volixibat arm were relatively high, with 9.1% of patients dropping out due to treatment-related adverse events, compared with 2.5% in the placebo arm. One patient in the placebo arm died. Volixibat treatment was associated with elevated levels of liver enzymes and bilirubin, which are biomarkers of damage to the organ.
“These patients don't have a normal liver,” Quan said during the investor call. Because PSC by itself “can be associated with fluctuations in some of the biochemical abnormalities,” she added, Mirum is now working with an independent team to sort out the full safety profile.
Volixibat is an inhibitor of a protein called the ileal bile acid transporter (IBAT), which regulates bile movement in the liver. Mirum already has extensive experience with this class of medicines; the company’s lead product is an IBAT inhibitor called Livmarli, which is approved for pruritus caused by other liver diseases.
There are currently no FDA-approved drugs to treat PSC. Mirum is also testing volixibat’s potential in another liver disease, primary biliary cholangitis (PBC), with topline data from a registrational phase 2b trial expected in the first quarter of next year.
In PBC, Mirum faces competition from GSK’s recently approved Lynavoy, which the British Big Pharma licensed to Italian outfit Alfasigma just before the FDA nod in a deal worth up to $690 million.