Rare Daily Staff
Mirum Pharmaceuticals has launched with $120 million in series A financing to support development of its lead drug candidate maralixibat for rare cholestatic liver diseases. Mirum will use the capital to initiate phase 3 confirmatory studies in patients with ALGS and PFIC in 2019.
The launch also comes with an agreement with Shire for exclusive global rights to develop and market maralixibat, for which Shire will receive an upfront payment, an equity position in Mirum, and potential future milestone payments and royalties. Mirum also acquired exclusive global rights to develop and market volixibat, another investigational therapeutic in the same class as maralixibat.
Maralixibat, an oral inhibitor of the apical sodium dependent bile acid transporter (ASBT), is being developed for Alagille syndrome (ALGS) and progressive familial intrahepatic cholestasis (PFIC). Alagille syndrome is a rare genetic disorder that can affect the liver, heart, skeleton, eyes and kidneys. Symptoms and severity of disease can vary greatly from one person to another; some individuals may have mild forms of the disorder, while others may have more serious forms. Common symptoms, which often develop during the first three months of life, include blockage of the flow of bile from the liver (cholestasis), jaundice, poor weight gain and growth, severe itching, and pale, loose stools.
Progressive familial intrahepatic cholestasis (PFIC) causes progressive liver disease, which typically leads to liver failure. In people with PFIC, liver cells are less able to secrete bile. The buildup of bile in liver cells causes liver disease in affected individuals. Signs and symptoms of PFIC typically begin in infancy. Patients experience severe itching, jaundice, failure to gain weight and grow at the expected rate, high blood pressure in the vein that supplies blood to the liver, and an enlarged liver and spleen.
Maralixibat is being tested to evaluate its ability to prevent accumulation of excess bile acids and control extreme itching associated with cholestatic liver diseases such as ALGS and PFIC. While Mirum plans to initially focus its efforts in these two pediatric indications, there is also potential to develop it for additional pediatric and adult cholestatic liver disease indications. Maralixibat has been administered to more than 230 cholestatic patients to date, providing an extensive safety data set.
“The interim data we are announcing today from the phase 2b ICONIC study in ALGS conducted by Shire underscores my continued confidence in maralixibat and its potential to help patients with these severely debilitating liver diseases,” said Mike Grey, chairman and CEO of Mirum. “The study leveraged an improved trial design and in its interim analysis, patients taking maralixibat had reductions in bile acids and pruritus compared to placebo. Additionally, in a single-arm, open-label phase 2 study, a subset of patients with PFIC2 responded to maralixibat, with a sustained (greater than 2 years for some) reduction or normalization of serum bile acids and reduction of pruritus. These results led to the FDA’s Breakthrough Therapy designation for patients with PFIC2. These clinical studies demonstrate the potential of maralixibat to significantly impact patients’ lives.”
Mike Grey has great faith in the maralixibat’s potential. The investigational drug was Lumena’s lead compound when the biotech was acquired by Shire in 2104 for $260 million. But it failed to live up to its potential in two mid-stage trials conducted by Shire. It took four years to get the trial design right, leading to the new interim analysis.
Mr. Grey has assembled an expert leadership team at Mirum with experience in drug development in the liver disease space from former companies Lumena and Tobira, and a stellar syndicate of investors. The financing was led by New Enterprise Associates with participation from Deerfield Management, Frazier Healthcare Partners, Novo Holdings, Pappas Capital, RiverVest Venture Partners, and Rock Springs Capital.
November 7, 2018
Photo: Mike Grey, chairman and CEO of Mirum