FOSTER CITY, Calif. — Mirum Pharmaceuticals, Inc. (Nasdaq: MIRM), a leading rare disease company, today announced topline results from the Phase 3 EXPAND study evaluating LIVMARLI® (maralixibat) for the treatment of cholestatic pruritus in patients aged 6 months or older with ultra-rare cholestatic liver diseases, including biliary atresia. The study met its primary endpoint and achieved statistical significance across all five prespecified secondary endpoints, including the three endpoints in patients with biliary atresia and a native liver.
The Phase 3 EXPAND study enrolled 52 patients, including 46 pediatric and six adult patients, who were randomized during the 20-week double-blind period to treatment with maralixibat 285 µg/kg twice daily (BID) or placebo.
Treatment with maralixibat demonstrated a statistically significant improvement in pruritus compared with placebo in the primary analysis population of pediatric patients. Maralixibat resulted in a mean 1.81-point improvement from baseline in average worst-daily ItchRO(Obs) severity score during Weeks 13-20 compared with a 0.83-point improvement for placebo, corresponding to a placebo-adjusted treatment difference of 0.98 points (p=0.0004). Maralixibat also resulted in a 70.1% reduction from baseline in serum bile acids (sBA), compared with 3.5% for placebo, corresponding to a 69.0% treatment effect versus placebo (p<0.0001). Key efficacy data from the Phase 3 EXPAND study are presented below in the Efficacy Results table.
Safety findings in EXPAND were consistent with prior clinical experience with maralixibat and no new safety signals were observed. Key safety data from the Phase 3 EXPAND study are presented below in the Safety Summary table.
“These results are especially important because patients with ultra-rare cholestatic liver diseases continue to face a significant burden from pruritus,” said Rob Myers, M.D., Chief Medical Officer at Mirum Pharmaceuticals. “The improvements in pruritus and reductions in serum bile acids observed in EXPAND reinforce the potential for maralixibat to address this unmet need and benefit a broader population of patients living with ultra-rare cholestatic liver diseases.”
“Cholestatic pruritus can be relentless and profoundly disruptive for people living with ultra-rare cholestatic liver diseases, yet treatment options remain limited,” said Jennifer Vittorio, M.D., FAASLD, Associate Professor of Pediatrics and Medical Director, Pediatric Liver Transplantation, NYU Langone Health. “The magnitude and consistency of improvements in pruritus and serum bile acid levels observed in EXPAND are compelling, including for patients with biliary atresia.”
“For families living with ultra-rare cholestatic liver diseases, the possibility of new treatment options brings tremendous hope,” said Jen Lau, MPH, Co-Founder and Executive Director of BARE, Inc. (Biliary Atresia Research and Education). “These results are meaningful for the biliary atresia community, where children and families continue to face significant challenges due to cholestatic pruritus. We are deeply grateful to the patients and families who participated in EXPAND and helped move this research forward.”
Mirum plans to submit a supplemental New Drug Application (sNDA) in the United States in the first half of 2027 based on EXPAND results.
Efficacy Results – Primary and Secondary Endpoints
|
|
Maralixibat 285 µg/kg BID |
Placebo |
Treatment Effect (MRX-PBO) |
p-value |
|
OVERALL STUDY ANALYSES |
||||
|
Primary Endpoint: Change in ItchRO(Obs) severity score (SE)b |
-1.81 (0.18)a |
-0.83 (0.18)a |
-0.98 |
0.0004 |
|
All Pediatric Population |
n=22 |
n=24
|
||
|
Percentage of days with pruritus improvement |
86.0% |
49.1% |
36.9% |
0.0008 |
|
All Pediatric Population |
n=22 |
n=24
|
||
|
Relative % change from baseline in total sBA |
-70.1% |
-3.5% |
-69.0%c |
<0.0001 |
|
Overall Population |
n=25 |
n=27
|
||
|
BILIARY ATRESIA (BA) WITH NATIVE LIVER SUBGROUP |
||||
|
Change in ItchRO(Obs) severity score (SE)b
|
-2.16 (0.21)a
n=11
|
-1.01 (0.18)a
n=14
|
-1.15 |
0.0002 |
|
Percentage of days with pruritus improvement
|
96.4%
n=11
|
52.2%
n=14
|
44.1% |
0.0045 |
|
Relative % change from baseline in total sBA
|
-75.5%
n=11
|
-9.0%
n=14
|
-73.1%c |
<0.0001 |
|
a LS means (SE). LS mean, SE, and p-values are from MMRM model. |
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bItchRO(Obs) = Itch Reported Outcome (Observer) is a Worst Itch 0-4 numerical rating scale. |
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csBA treatment effects were estimated using log-transformed values and back-transformed to the original scale; therefore, they are not calculated as the arithmetic difference between treatment groups. |
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The primary endpoint represents change from baseline to the average of Weeks 13-20. Serum bile acid (sBA) endpoints represent change from baseline to the average of Weeks 12 and 20. Pruritus improvement was defined over Weeks 13-20 as a worst-daily ItchRO(Obs) score ≤1 or a decrease of ≥1 point from baseline. The All Pediatric Population included randomized participants aged 18 years or younger who received at least one dose of study drug and had at least one ItchRO(Obs) score. |
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Safety Summary – 20-Week Double-Blind Period
The Safety Population includes all randomized participants who received at least one dose of maralixibat or placebo; participants were analyzed according to the treatment received.
|
Participants with, n (%) |
Maralixibat 285 µg/kg BID (n=25) |
Placebo (n=27) |
|
Any treatment-emergent adverse event (TEAE) |
24 (96.0) |
26 (96.3) |
|
Grade 3 or higher TEAEs |
6 (24.0) |
6 (22.2) |
|
Related to study drug |
1 (4.0) |
0 |
|
Serious TEAEs |
5 (20.0) |
5 (18.5) |
|
TEAE that led to death |
0 |
0 |
|
TEAE that led to premature discontinuation from study |
1 (4.0) |
0 |
|
TEAEs of interest |
|
|
|
Diarrhea |
16 (64.0) |
3 (11.1) |
|
Abdominal pain |
5 (20.0) |
4 (14.8) |
|
ALT increased |
2 (8.0) |
1 (3.7) |
|
Serious adverse events (SAEs) in MRX-treated patients: pneumonia, pyrexia, large intestine infection, acute kidney injury, viral infection with bronchiolitis; none related. SAEs in placebo-treated patients: pneumonia, pancytopenia, sepsis, forearm fracture, cholangitis. |
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Conference Call to Discuss EXPAND Topline Results
Mirum will host a conference call today, Monday, October 12, at 8:30 a.m. ET to share topline results from the Phase 3 EXPAND study of LIVMARLI® (maralixibat) in additional ultra-rare cholestatic liver diseases. Join the call using the following details:
Conference Call Details:
US/Toll-Free: +1 833 461 5787
International: +1 585 542 9983
Access Code: 486697901
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 the EXPAND Phase 3 Study
EXPAND is a Phase 3, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of LIVMARLI® (maralixibat) oral solution in children aged 6 months and older and adults with cholestatic pruritus associated with ultra-rare cholestatic liver diseases. These diseases include biliary atresia and other rare conditions for which LIVMARLI is not currently approved.
The primary endpoint is change from baseline in average worst-daily ItchRO(Obs) severity score during Weeks 13-20. Secondary efficacy measures include changes in serum bile acid levels and days with pruritus improvement, with corresponding prespecified analyses of pruritus severity, serum bile acids and days with pruritus improvement in patients with biliary atresia and a native liver.
About LIVMARLI® (maralixibat) oral solution and LIVMARLI® (maralixibat) tablets
LIVMARLI® (maralixibat) is an orally administered, ileal bile acid transporter (IBAT) inhibitor approved by the U.S. Food and Drug Administration for two pediatric cholestatic liver diseases. It is approved for the treatment of cholestatic pruritus in patients with Alagille syndrome (ALGS) in the U.S. three months of age and older and in Europe for patients two months of age and older. It is also approved in the U.S. for the treatment of cholestatic pruritus in patients with progressive familial intrahepatic cholestasis (PFIC) 12 months of age and older and in Europe for the treatment of PFIC in patients three months of age and older. For more information for U.S. residents, please visit LIVMARLI.com.
Maralixibat has received Breakthrough Therapy designation for ALGS and PFIC type 2 and orphan drug designation for the treatment of ALGS, PFIC, and biliary atresia. LIVMARLI has been evaluated in the Phase 3 EXPAND study in additional settings of cholestatic pruritus. To learn more about ongoing clinical trials with LIVMARLI, please visit Mirum’s clinical trials section on the company’s website.
IMPORTANT SAFETY INFORMATION
Limitation of Use: LIVMARLI is not for use in PFIC type 2 patients who have a severe defect in the bile salt export pump (BSEP) protein.
LIVMARLI can cause side effects, including:
Liver injury. Changes in certain liver tests are common in patients with ALGS and PFIC but can worsen during treatment. These changes may be a sign of liver injury. In PFIC, this can be serious or may lead to liver transplant or death. Your healthcare provider should do blood tests and physical exams before starting and during treatment to check your liver function. Tell your healthcare provider right away if you get any signs or symptoms of liver problems, including nausea or vomiting, skin or the white part of the eye turns yellow, dark or brown urine, pain on the right side of the stomach (abdomen), bloating in your stomach area, loss of appetite or bleeding or bruising more easily than normal.
Stomach and intestinal (gastrointestinal) problems. LIVMARLI can cause stomach and intestinal problems, including diarrhea and stomach pain. Your healthcare provider may advise you to monitor for new or worsening stomach problems including stomach pain, diarrhea, blood in your stool or vomiting. Tell your healthcare provider right away if you have any of these symptoms more often or more severely than normal for you.
A condition called Fat Soluble Vitamin (FSV) Deficiency caused by low levels of certain vitamins (vitamin A, D, E, and K) stored in body fat is common in patients with ALGS and PFIC but may worsen during treatment. Your healthcare provider should do blood tests before starting and during treatment and may monitor for bone fractures and bleeding which have been reported as common side effects.
US Prescribing Information
EU SmPC
Canadian Product Monograph
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 focuses on rare liver and rare genetic diseases, where it has built deep expertise and strong connections to patient communities. The company’s commercial portfolio includes LIVMARLI® (maralixibat) for Alagille syndrome (ALGS) and progressive familial intrahepatic cholestasis (PFIC), ATEBRIOZ™ (zilurgisertib) for fibrodysplasia ossificans progressiva (FOP), 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 https://mirumpharma.com/ and follow Mirum on Facebook, LinkedIn, Instagram and X.
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