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First potential therapy for primary sclerosing cholangitis clears Phase 2b

First potential therapy for primary sclerosing cholangitis clears Phase 2b

New Capabilities
By Newzino Staff |

Mirum's volixibat sets up an FDA filing later this year for a liver disease with no approved drugs

August 31st, 2026: Pre-NDA meeting with FDA expected

Overview

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, that drought moved closer to ending: Mirum Pharmaceuticals reported that its experimental pill volixibat hit the primary endpoint of its Phase 2b VISTAS trial, cutting the relentless itch that defines the disease by a wide margin over placebo.

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.

Key Indicators

0
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.

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People Involved

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

Organizations Involved

Mirum Pharmaceuticals
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
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

  1. Pre-NDA meeting with FDA expected

    Regulatory

    Mirum has a pre-NDA meeting scheduled with the FDA for summer 2026 to confirm the contents of its filing package.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

Scenarios

1

FDA approves volixibat in 2027 as first PSC therapy

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.

2

FDA requires a confirmatory Phase 3 before approval

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.

3

Liver enzyme signal forces a narrower label

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

Maralixibat approval for Alagille syndrome (2021)

September 2021

What Happened

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.

Outcome

Short Term

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

Long Term

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 It's Relevant Today

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.

Elafibranor approval for primary biliary cholangitis (2024)

June 2024

What Happened

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.

Outcome

Short Term

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

Long Term

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 It's Relevant Today

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.

Simtuzumab failure in PSC (2017)

2017

What Happened

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.

Outcome

Short Term

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

Long Term

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 It's Relevant Today

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.

Sources

(9)
+3
Business Wire U.S. Securities and Exchange Commission StockTitan HCPLive Drugs (PubMed Central) Ipsen Gastroenterology (PubMed) NCBI Bookshelf PSC Partners Registry