First potential therapy for primary sclerosing cholangitis clears Phase 2b

Overview

Updated May 31

For the roughly 30,000 Americans living with primary sclerosing cholangitis (PSC), the U.S. Food and Drug Administration has never approved a single drug. On May 4, 2026, Mirum Pharmaceuticals reported that its experimental pill volixibat hit the primary endpoint of its Phase 2b VISTAS trial, reducing the relentless itch far more than placebo.

PSC is a chronic disease that scars the bile ducts and leads to liver transplant in many patients. Its most disabling symptom is pruritus, a deep and intractable itch caused by bile acids backing up into the bloodstream. With the VISTAS data, Mirum says it will meet with the FDA this summer and file a New Drug Application (NDA) in the second half of 2026, putting a first PSC therapy within reach of approval by 2027.

Why it matters

If volixibat wins FDA approval, tens of thousands of PSC patients gain the first drug ever targeted at their disease, after decades of failed trials.

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Key Indicators

FDA-approved PSC therapies

No drug has ever cleared the FDA for primary sclerosing cholangitis; ursodeoxycholic acid is used off-label without changing the disease course.

p<0.0001

VISTAS primary endpoint

Volixibat produced a 1.64-point placebo-adjusted reduction on the Adult ItchRO scale in moderate-to-severe pruritus.

55.6%

Volixibat itch responders

Share of treated patients hitting a clinically meaningful 2-point itch drop, versus 26.3% on placebo.

111

Primary cohort patients

Number of moderate-to-severe pruritus patients in the registrational analysis cohort; another 47 had mild itch.

~17%

Share of global liver transplants

Proportion of liver transplants attributable to PSC despite a US prevalence of only 6–16 per 100,000 people.

2H 2026

Planned NDA submission

Mirum's target window for filing volixibat with the FDA, after a pre-NDA meeting scheduled for summer 2026.

Voices

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People Involved

Chris Peetz

Co-founder and Chief Executive Officer, Mirum Pharmaceuticals

Leading Mirum's push to file volixibat with the FDA in late 2026

Organizations Involved

Mirum Pharmaceuticals

Biopharmaceutical company

Sponsor of volixibat; targeting NDA filing in 2H 2026

A Foster City, California biotech focused on rare cholestatic liver diseases.

U.S. Food and Drug Administration

Federal regulatory agency

Pre-NDA meeting with Mirum scheduled for summer 2026

The federal agency that approves human drugs in the United States.

Timeline

April 2018 August 2026

7 events Latest: August 31st, 2026 · 1 week ago

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August 2026
Pre-NDA meeting with FDA expected
Latest Regulatory

Mirum has a pre-NDA meeting scheduled with the FDA for summer 2026 to confirm the contents of its filing package.
August 31st, 2026
May 2026
Volixibat hits primary endpoint in VISTAS
Clinical Trial

Mirum reports a 1.64-point placebo-adjusted reduction on the Adult ItchRO scale (p<0.0001) in moderate-to-severe pruritus, with 55.6% of treated patients hitting a clinically meaningful response versus 26.3% on placebo.
May 4th, 2026 • 07:00 ET
September 2025
VISTAS completes enrollment
Clinical Trial

Mirum finishes enrolling 158 PSC patients in the Phase 2b VISTAS study, splitting them into moderate-to-severe and mild pruritus cohorts.
September 1st, 2025
June 2024
Iqirvo approved as first new PBC drug in a decade
Regulatory

FDA grants accelerated approval to Ipsen's elafibranor for primary biliary cholangitis, signaling a broader regulatory thaw for cholestatic liver diseases.
June 10th, 2024
March 2024
Livmarli wins second indication in PFIC
Regulatory

FDA expands maralixibat's label to progressive familial intrahepatic cholestasis based on the Phase 3 MARCH trial, the largest randomized study ever run in PFIC.
March 13th, 2024
September 2021
FDA approves maralixibat for Alagille syndrome
Regulatory

Mirum's first IBAT inhibitor (Livmarli) becomes the first FDA-approved drug for cholestatic pruritus in Alagille syndrome, validating the drug class.
September 29th, 2021
April 2018
Mirum founded around Shire's cholestatic disease portfolio
Corporate

Mirum Pharmaceuticals incorporates and licenses maralixibat and volixibat — two IBAT inhibitors that Shire had shelved — to pursue rare liver diseases.
April 15th, 2018

Scenarios

FDA approves volixibat in 2027 as first PSC therapy

Likely

Discussed by: Mirum management; sell-side analysts at H.C. Wainwright and Stifel

Mirum files its NDA in late 2026, the FDA accepts symptomatic pruritus relief as the basis for accelerated approval — as it did for elafibranor in PBC — and volixibat clears review in 2027. PSC patients gain access to the first drug ever indicated for their disease, and Mirum extends its IBAT franchise from pediatric rare diseases into a much larger adult market.

FDA requires a confirmatory Phase 3 before approval

Possible

Discussed by: Hepatology specialists writing in HCPLive; cautious sell-side analysts

The agency accepts the VISTAS data as supportive but asks for a larger Phase 3 trial confirming durability of the itch benefit and clarifying the gastrointestinal and liver enzyme safety signals seen with IBAT inhibition. Approval slides to 2029 or later, and Mirum's PSC revenue is pushed out by years.

Liver enzyme signal forces a narrower label

Possible

Discussed by: Clinicians flagging ALT and bilirubin elevations in HCPLive coverage

FDA reviewers approve volixibat but restrict it to patients with the most severe pruritus, mandate boxed warnings on hepatotoxicity, or require frequent monitoring. The drug reaches market but the addressable population shrinks materially from the ~30,000 US PSC patients many investors are modeling.

Historical Context

3 moments from history that rhyme with this story — and how they unfolded.

2017

Simtuzumab failure in PSC (2017)

Gilead's simtuzumab, an antibody targeting fibrosis-driving enzyme LOXL2, failed a 234-patient Phase 2b trial in PSC. Neither dose reduced fibrosis stage, slowed progression to cirrhosis, or cut clinical events versus placebo.

Then

Gilead discontinued the program. The trial reinforced PSC's reputation as a graveyard for hepatology drug development.

Now

Repeated failures of fibrosis- and bile-acid-modifying drugs (simtuzumab, vancomycin, obeticholic acid) pushed companies and the FDA toward symptom-based endpoints — the framework volixibat is now using.

Why this matters now

Simtuzumab is a reminder that PSC has broken many drugs before, and that volixibat's win is significant precisely because the prior list of failures is so long. It also explains why Mirum chose pruritus rather than fibrosis or transplant-free survival as the primary endpoint.

September 2021

Maralixibat approval for Alagille syndrome (2021)

The FDA approved Mirum's maralixibat (Livmarli) as the first-ever therapy for cholestatic pruritus in Alagille syndrome, a rare pediatric liver disease. Approval was based on the ICONIC study in 86 patients, using patient-reported itch as the registrational endpoint.

Then

Mirum, then a three-year-old company, secured its first commercial product and validated the IBAT inhibitor mechanism. Livmarli generated meaningful revenue almost immediately.

Now

The approval established a regulatory precedent for using symptomatic itch relief as the basis for approval in rare cholestatic liver diseases — the same path Mirum is now walking with volixibat in PSC.

Why this matters now

Volixibat is from the same drug class as maralixibat and is being filed under a similar itch-based regulatory framework. The Alagille approval is the closest analog for what Mirum is asking the FDA to do again in PSC.

June 2024

Elafibranor approval for primary biliary cholangitis (2024)

Ipsen's Iqirvo (elafibranor) won FDA accelerated approval as the first new drug for primary biliary cholangitis (PBC) in nearly a decade, based on biochemical improvements in the Phase 3 ELATIVE trial. PBC, like PSC, is a chronic cholestatic liver disease that often progresses to transplant.

Then

Ipsen launched Iqirvo into a starved market and the FDA signaled a willingness to clear cholestatic disease drugs on surrogate or symptomatic endpoints.

Now

Elafibranor's approval ended a long stretch in which cholestatic liver diseases were considered regulatory dead ends and reopened biotech investment in the category.

Why this matters now

Iqirvo is the most recent regulatory comparator for what Mirum is attempting: an accelerated approval in a rare cholestatic liver disease with no good options. Its precedent makes the FDA path for volixibat substantially more credible than it would have been five years ago.