In the biopharmaceutical field, stories full of ups and downs often unfold, and Mike Grey’s rescue of Maralixibat is undoubtedly one of the most gripping chapters.
Mike Grey is a seasoned veteran in the pharmaceutical industry with 40 years of profound experience. He has held senior positions in multiple companies, such as President and CEO of SGX Pharmaceuticals (acquired by Eli Lilly in 2008), President and CEO of Trega Biosciences (acquired by Lion Bioscience in 2001), and President of Biochem Therapeutic. Between 2011 and 2014, he served as President and CEO of Lumena, an experience that laid the foundation for the later pipeline development of Maralixibat’s new owner, Mirum Pharmaceuticals.
In 2014, Shire (now acquired by Takeda) acquired Lumena Pharmaceuticals for $260 million, gaining Maralixibat (then codenamed LUM001). At that time, Shire had high hopes for Maralixibat to make a breakthrough in the treatment of rare liver diseases. However, subsequent R&D progress suffered a severe setback, and Maralixibat fell into a four-year “freeze” period.
In 2018, Mike Grey founded Mirum Pharmaceuticals. After giving up control of the drug for four years, leveraging new topline data, he successfully obtained the global exclusive license for Maralixibat from Shire and continued research. Mirum Pharmaceuticals thus embarked on a journey in rare disease drug development. With this success, the company raised $120 million in Series A financing, injecting strong momentum into its subsequent development.
Maralixibat, marketed as LIVMARLI, is an oral, once-daily ileal bile acid transporter (IBAT) inhibitor. Its mechanism of action is to block the enterohepatic circulation of bile acids, lowering bile acid levels in the liver and serum, thereby reducing bile acid-mediated liver damage and alleviating itching symptoms.
Regarding indications, Maralixibat is the first approved drug for treating cholestatic pruritus in patients with Alagille Syndrome (ALGS). In the U.S., it is approved for cholestatic pruritus in ALGS patients aged 3 months and older; in the EU for ALGS patients aged 2 months and older; in Canada for ALGS patients aged 1 to 18 years; and in China, Israel, and South Korea for ALGS patients aged 1 year and older. In China, it is commercialized by Beihai Kangcheng, in Israel by Neopharm, and in South Korea by GC Pharma.
Additionally, the FDA approved Maralixibat for treating cholestatic pruritus in progressive familial intrahepatic cholestasis (PFIC) patients aged 12 months and older, and it is also approved in the EU for PFIC patients aged 3 months and older.
The company is currently advancing Maralixibat for other indications. Through a Phase 3 clinical trial named EXPAND, it is exploring treatment of pruritus in rare cholestatic conditions beyond ALGS, PFIC, PSC, intrahepatic cholestasis of pregnancy, and PBC, with recruitment expected to complete in 2026.
Another Mirum Pharmaceuticals approved product, CTEXLI (chenodiol) tablets, also called chenodeoxycholic acid (CDCA), is a naturally occurring bile acid initially approved for treating radiopaque gallstones. Mirum Pharmaceuticals discovered its potential in treating cerebrotendinous xanthomatosis (CTX).
Its mechanism is to supplement the bile acid deficient in patients, helping clear toxic cholesterol metabolite deposits and effectively alleviating CTX-related clinical symptoms. CTX is an extremely rare genetic metabolic disease caused by mutations in the CYP27A1 gene, leading to a deficiency in a key enzyme for fat breakdown. Without timely and effective treatment, patients suffer from chronic diarrhea, juvenile bilateral cataracts, tendon xanthomas, and neurological deterioration.
In June 2024, Mirum Pharmaceuticals submitted an NDA to the FDA for chenodiol to treat CTX patients. The submission was mainly based on results from the Phase 3 RESTORE clinical trial, which evaluated chenodiol in adult CTX patients. The study met its primary endpoint, showing a highly statistically significant reduction in cholestanol levels (p<0.0001); at the end of the randomized double-blind withdrawal period, the cholestanol difference between placebo and chenodiol groups was 20-fold; RESTORE also demonstrated significant improvements in patients’ serum cholestanol levels.
On February 21, 2025, the FDA officially approved chenodiol for marketing to treat adult CTX, bringing new hope to CTX patients and marking another major breakthrough for the company in rare disease treatment.
Another product, CHOLBAM (cholic acid capsules), was initially developed by Asklepion Pharmaceuticals and approved in March 2015. In 2015, Retrophin acquired Cholbam from Asklepion Pharmaceuticals. Later, Mirum Pharmaceuticals acquired the bile acid product portfolio, including Cholbam, from Retrophin.
Cholbam is mainly used to treat children and adults with bile acid synthesis disorders caused by single enzyme defects and can also serve as adjunct therapy for peroxisomal disorders (including PBD-ZSD) patients. It works by supplementing the bile acid deficiency in patients, regulating bile acid metabolism balance, and thereby improving related symptoms.
Currently, Cholbam is stably marketed, providing effective treatment options for related rare disease patients, holding a certain market share in bile acid synthesis disorders and peroxisomal disorder treatment fields, and generating a steady revenue stream for the company.
Volixibat is an oral, minimally absorbed drug that also aims to inhibit IBAT, with a mechanism similar to LIVMARLI but with different drug properties, potentially providing more suitable treatment options for different patient populations. It is currently being evaluated in two Phase 2b clinical trials: the VISTAS trial for primary sclerosing cholangitis (PSC) and the VANTAGE trial for primary biliary cholangitis (PBC).
PSC is a serious idiopathic chronic cholestatic liver disease characterized by progressive inflammation and destruction of bile ducts, which can lead to life-threatening complications. Up to 65% of PSC patients experience pruritus during the disease course.
The VISTAS trial is an adaptive, randomized study designed to assess the effects of Volixibat on pruritus, serum bile acids (sBA), and fibrosis markers in PSC patients with pruritus. Enrollment is expected to complete in Q3 2025, with topline data anticipated in Q2 2026.
PBC is a chronic, rare cholestatic liver disease characterized by immune-mediated destruction of intrahepatic bile ducts, causing progressive hepatobiliary flow obstruction. This results in increased bile acid concentration in the liver, triggering local inflammation, progressing to liver fibrosis, cirrhosis, and liver function decompensation. Enrollment in the VANTAGE study is expected to complete in 2026.
MRM-3379 is a selective PDE4D inhibitor advancing for the treatment of Fragile X Syndrome (FXS).
FXS is a genetic disorder caused by abnormalities in the FMR1 gene, mainly due to abnormal expansion of CGG repeats in the 5' untranslated region of the FMR1 gene, resulting in gene silencing and lack of the fragile X mental retardation protein, which affects normal development and function of neurons, causing a range of cognitive, behavioral, and neurodevelopmental symptoms.
PDE4D is highly active in brain regions important for learning, memory, and mood regulation, breaking down cyclic AMP (cAMP), a key signaling molecule between neurons. FXS patients have lower cAMP levels than normal. MRM-3379 selectively inhibits PDE4D activity, increasing brain cAMP levels, helping restore neuronal communication networks disrupted by the disease, potentially alleviating FXS symptoms.
The Phase 2 clinical trial for MRM-3379 is expected to start this year.
On May 7, Maralixibat’s owner Mirum Pharmaceuticals reported its Q1 revenue for 2025. As of March 31, 2025, the company had unrestricted cash, cash equivalents, and investments totaling $298.6 million. The market cap before publication was approximately $2.2 billion.
The company’s global product net sales for Q1 2025 were $111.6 million, compared with $68.9 million in the same period last year. Maralixibat net sales reached $73.2 million, and bile acid drug product net sales were $28.4 million. Total operating expenses were $126.8 million, up from $95.7 million the previous year.
According to last year’s data, 2024 full-year product net sales were $336.4 million, compared with $178.9 million the previous year. Maralixibat net sales totaled $213.3 million in 2024, with bile acid drug product net sales at $123.1 million. Total operating expenses for 2024 were $424.5 million, including $79.4 million of non-cash stock compensation, amortization, and other non-cash expenses.
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