Mirum Pharmaceuticals Announces Primary Endpoint Met in VISTAS Study of Volixibat in Patients with Primary Sclerosing Cholangitis

- Statistically significant and clinically meaningful 2.72 point reduction from baseline and 1.64 point placebo-adjusted (p=<0.0001) reduction in primary endpoint of cholestatic pruritus

- Pre-NDA meeting with the U.S. Food and Drug Administration (FDA) scheduled for summer 2026

- Full results to be presented in late-breaking oral presentation at the EASL International Liver Congress 2026

- Mirum to host conference call to discuss Mirum's recent clinical readouts, today, May 4 at 8:30 am ET

Mirum Pharmaceuticals, Inc. (NASDAQ:MIRM), a leading rare disease company, today announced the primary endpoint was met in the VISTAS Phase 2b study evaluating volixibat, an investigational oral ileal bile acid transporter (IBAT) inhibitor, in patients with primary sclerosing cholangitis (PSC).

The VISTAS Phase 2b study included 158 patients with PSC who were assigned to either a primary analysis cohort (moderate to severe itch; n=111) or a secondary analysis cohort (mild itch; n=47) based on itch severity at baseline, as measured by the Adult Itch Reported Outcome (ItchRO) scale. Patients in both cohorts were treated with volixibat 20 mg twice daily (BID) or placebo. Per the study protocol, the endpoint was evaluated in the primary analysis cohort.

The results of the VISTAS Phase 2b study support the potential for volixibat to become the first treatment for cholestatic pruritus in patients with PSC. In the primary analysis cohort, treatment with volixibat demonstrated a robust 2.72 point improvement in pruritus and a placebo-adjusted difference of 1.64 points in the primary endpoint (p<0.0001), as measured by the Adult ItchRO scale, reflecting change from baseline to the average of the last 12 weeks of treatment. Statistically significant improvements in pruritus were observed within two weeks of treatment and were also observed in the secondary cohort of patients with mild itch at baseline. Key efficacy data from the VISTAS Phase 2b study are presented below in the Change from Baseline (Primary Analysis Cohort) table.

Volixibat's safety profile was generally consistent with the known effects of IBAT inhibition, characterized primarily by gastrointestinal adverse events and elevations in liver laboratory parameters, including alanine aminotransferase (ALT) and bilirubin. Key safety data from the VISTAS Phase 2b study are presented below in the Safety Summary (Primary and Secondary Cohorts) table.

Mirum has a pre-New Drug Application (NDA) meeting for volixibat in PSC scheduled with the U.S. FDA in summer 2026, with a planned NDA submission in the second half of 2026.

"These results mark an important milestone for the PSC community, where there are currently no approved therapies," said Joanne Quan, M.D., Chief Medical Officer at Mirum. "In a disease that has been historically difficult to study and treat, VISTAS delivered a clear and compelling efficacy signal. The observed statistically significant and clinically meaningful reductions in pruritus demonstrate the potential for volixibat to address one of PSC's most burdensome and defining symptoms."

"Cholestatic pruritus is one of the most common symptoms in PSC, which remains a challenging disease to manage," said Kris Kowdley, M.D., Director, Liver Institute Northwest, Professor, Elson S. Floyd College of Medicine at Washington State University and an investigator for the VISTAS study. "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."

"After decades of commitment from patients, families and researchers participating in PSC studies, these results represent real hope for what could become the first approved treatment," said Ricky Safer, Founder and CEO of PSC Partners Seeking a Cure. "For many patients, the itch associated with PSC is constant and deeply disruptive – affecting sleep, daily activities and overall quality of life. Seeing meaningful progress in reducing this burden is incredibly encouraging for a community that has long had limited options."

The full results from the VISTAS Phase 2b study will be presented in a late-breaking oral presentation at the European Association for the Study of the Liver (EASL) International Liver Congress on May 30 at 2:15 p.m. CEST.

Mirum also now expects topline data from its VANTAGE Phase 2b study of volixibat in primary biliary cholangitis (PBC) in the first quarter of 2027.

Change from Baseline (Primary Analysis Cohort)

Safety Summary (Primary and Secondary Cohorts)

Conference Call to Discuss Mirum's Recent Clinical Readouts

Mirum will host a conference call today, Monday, May 4, at 8:30 am ET to discuss topline results from the VISTAS Phase 2b study, along with previously announced topline results from the Phase 2b portion of the AZURE-1 study of brelovitug in HDV. Join the call using the following details:

Conference Call Details:

US/Toll-Free: + 1 833 461 5787

International: +1 585 542 9983

Access Code: 151345102

You may also access the call via webcast by visiting the Investors section of Mirum's corporate website. The archived webcast will be available for replay.

About Volixibat

Volixibat is an oral, minimally absorbed agent designed to selectively inhibit the ileal bile acid transporter (IBAT). Volixibat may offer a novel approach in the treatment of adult cholestatic diseases by blocking the recycling of bile acids, through inhibition of IBAT, thereby reducing bile acids systemically and in the liver. Volixibat is currently being evaluated in phase 2b studies for primary sclerosing cholangitis (PSC) (VISTAS study) and primary biliary cholangitis (PBC) (VANTAGE study). In 2024, the Phase 2b VANTAGE study of volixibat in PBC met the primary endpoint. No new safety signals were observed, and the most common adverse event was diarrhea with all cases mild to moderate. Volixibat has been granted FDA Breakthrough Therapy designation for the treatment of PBC.

About the VISTAS Phase 2b Study

VISTAS is a global, randomized, double-blind, placebo-controlled Phase 2b study evaluating the efficacy and safety of volixibat in patients with cholestatic pruritus caused by primary sclerosing cholangitis (PSC). The primary endpoint of the study was mean change in weekly averaged daily itch score, as measured by the adult ItchRO scale (an 11-point scale where 0 = no itch and 10 = worst itch imaginable), from baseline to Week 28, defined as the average of the last 12 weeks of treatment.

About Primary Sclerosing Cholangitis (PSC)

PSC is a rare, chronic, progressive liver disease in which the bile ducts inside and outside the liver become inflamed, scarred, and narrowed over time. This bile duct damage often leads to bile accumulation, cholangitis, liver injury, and eventually liver failure. The disease impacts an estimated 30,000 patients in the United States. Patients with PSC experience a heavy symptom burden, with pruritus (itching), fatigue, and abdominal pain that may be debilitating and life-altering. Beyond symptom burden, PSC is associated with increased risk of bile duct cancer and need for liver transplantation. There are currently no approved therapies for PSC.

About Mirum Pharmaceuticals

Mirum Pharmaceuticals (NASDAQ:MIRM) is a leading rare disease company with a global footprint of approved products and a broad pipeline of investigational medicines. Purpose-built to bring forward breakthrough medicines for people with overlooked conditions, Mirum combines deep rare disease expertise with strong connections to patient communities.

The company's commercial portfolio includes LIVMARLI^® (maralixibat) for Alagille syndrome (ALGS) and progressive familial intrahepatic cholestasis (PFIC), CHOLBAM^® (cholic acid) for bile-acid synthesis disorders, and CTEXLI^® (chenodiol) for cerebrotendinous xanthomatosis (CTX).

Mirum's clinical-stage pipeline includes volixibat, an IBAT inhibitor in late-stage development for primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC), brelovitug, a fully human monoclonal antibody in late-stage development for chronic hepatitis delta virus (HDV) and MRM-3379, a PDE4D inhibitor being evaluated for Fragile X syndrome (FXS).

Mirum's success is driven by a team dedicated to advancing high impact medicines through strategic development, disciplined execution and purposeful collaboration across the rare disease ecosystem. Learn more at www.mirumpharma.com and follow Mirum on Facebook, LinkedIn, Instagram and X.

Forward-Looking Statements

Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include statements regarding, among other things, expected occurrence and timing of potential meetings with the FDA and NDA submission, the potential benefits of volixibat, the use of cholestatic pruritus as an important endpoint in PSC and the success or approval of any potential regulatory submission for volixibat. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as "anticipate," "expected," "will," "could," "would," "potential," "continue," "plans," "intended," "believe," and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Mirum's current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks and uncertainties that the FDA and other health authorities may not find Mirum's clinical data sufficient for approval; risks with the development of investigational medicines generally, including the failure of future studies to generate the same or similar data as prior studies; and the risk that potential estimated prevalences are materially inaccurate; the risks and uncertainties associated with Mirum's business in general, the impact of geopolitical and macroeconomic events, and the other risks described in Mirum's Annual Report for the year ended December 31, 2025, filed with the Securities and Exchange Commission on February 25, 2026, and subsequent filings with the Securities and Exchange Commission, which are available at www.sec.gov. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on management's assumptions and estimates as of such date. Mirum undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law.

Mirum, ItchRO and the Mirum logo are trademarks of Mirum Pharmaceuticals, Inc.

View source version on businesswire.com: https://www.businesswire.com/news/home/20260504069726/en/

Investor Contact:

Andrew McKibben

ir@mirumpharma.com

Media Contact:

Meredith Kiernan

media@mirumpharma.com