Mirum Pharmaceuticals (MIRM) Study Result summary

Interim study results and design

• Interim analyses for VISTAS (PSC) and VANTAGE (PBC) phase II-B studies of volixibat showed positive efficacy and safety outcomes, meeting prespecified thresholds for continuation at the 20 mg b.i.d. dose.

• VISTAS is a 28-week, double-blind, placebo-controlled, adaptive study; VANTAGE mirrors this design but had an open interim analysis and plans to enroll up to 200 patients for confirmatory analysis.

• Both studies target rare cholestatic liver diseases with significant unmet need: ~230,000 PBC and ~54,000 PSC patients in the US and Europe, most experiencing pruritus.

• Enrollment for VISTAS is expected to complete in H2 2025; VANTAGE will expand to 100 sites in 14 countries, with enrollment completion expected in 2026.

• Baseline characteristics in VANTAGE were well balanced, with mean ages in the 50s-60s and high female representation.

Efficacy and safety findings

• Volixibat demonstrated rapid and significant pruritus reduction, with effects observed as early as week one and LS mean change in Adult ItchRO score of -3.84 for 20mg and -3.79 for 80mg, both p<0.0001 vs baseline.

• Both doses in VANTAGE showed similar efficacy and safety, leading to selection of 20 mg b.i.d. for further study.

• Improvements were also seen in fatigue and reductions in serum bile acids, with 75% of patients achieving >50% reduction; no significant changes in liver enzymes or alkaline phosphatase were observed.

• The most common adverse event was mild to moderate, transient diarrhea (77% incidence), with one discontinuation due to diarrhea.

• Four serious adverse events occurred, including one on placebo; no new safety signals were identified.

Regulatory and strategic implications

• Both studies incorporated regulatory feedback, and if final results confirm interim findings, they could support NDA filings for volixibat in both indications.

• Pruritus is accepted as a registrational endpoint by the FDA for both PSC and PBC, supporting broad potential label and use across disease stages.

• The safety database and study sizes align with FDA guidance for full approval, not accelerated approval.

• Volixibat's nonclinical safety profile is favorable, with minimal systemic exposure.

• The program aims to position volixibat as a treatment option for both first- and second-line PBC patients, with broad eligibility regardless of baseline alkaline phosphatase.