Mirum’s Volixibat Achieves Positive Interim Analyses in VANTAGE PBC and VISTAS PSC Studies
Mirum Pharmaceuticals (Nasdaq: MIRM) announced positive interim results from two Phase 2b studies evaluating volixibat in patients with primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC).
In the VANTAGE PBC study, volixibat demonstrated a statistically significant improvement in pruritus with a 3.82 point reduction (p<0.0001) and a 2.32 point placebo-adjusted difference (p=0.0026). 75% of patients on volixibat achieved over 50% reduction in serum bile acids. Fatigue also improved significantly at week 16, with no new safety signals. The most common adverse event was mild to moderate diarrhea (77%).
The VISTAS PSC study exceeded the efficacy threshold for continuation. The independent data review committee recommended continuing the study with the current dose of 20 mg twice daily. Mirum will discuss these findings in a conference call on June 17 at 8:30 a.m. ET.
- Significant 3.82 point reduction in pruritus in VANTAGE PBC study.
- 2.32 point placebo-adjusted improvement (p=0.0026) in VANTAGE PBC study.
- 75% reduction in serum bile acids for 75% of volixibat patients.
- Significant improvement in fatigue at week 16 with volixibat.
- No new safety signals observed in VANTAGE PBC study.
- VISTAS PSC study met efficacy threshold for continuation.
- 77% of patients experienced mild to moderate diarrhea in VANTAGE PBC study.
- One case of diarrhea resulted in discontinuation in VANTAGE PBC study.
- Four serious adverse events reported, including one in placebo arm.
Insights
The interim results from the VANTAGE and VISTAS studies suggest promising potential for Mirum’s volixibat in treating primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Both conditions are rare liver diseases where pruritus (itching) and fatigue significantly impair patients' quality of life. The reported improvement in pruritus, as measured by the Adult ItchRO scale, is noteworthy. A placebo-adjusted reduction of 2.32 points with a statistical significance of p=0.0026 indicates a strong effect of the drug.
From a clinical perspective, this data is encouraging. The high placebo-adjusted difference and the fact that 75% of patients on volixibat achieved a significant reduction in serum bile acids are positive indicators. Importantly, no new safety signals were observed and adverse events like diarrhea were mild to moderate, suggesting the drug is well-tolerated.
For a retail investor, these findings provide a solid basis for optimism regarding volixibat’s future approval and market potential. However, it is essential to remain cautious until final data is available from the ongoing trials. The continuation of the trials with the existing dose further underscores the drug’s potential, but vigilance is required to monitor long-term efficacy and safety.
Given the positive interim results, Mirum Pharmaceuticals stands to strengthen its position in the market for rare liver diseases. The unmet medical needs in PBC and PSC offer a significant market opportunity. The potential approval and commercialization of volixibat could position Mirum as a key player in this niche market. This could attract further investment and partnerships, enhancing the company’s financial health.
The statistically significant improvement in pruritus and the favorable safety profile are critical selling points. The market for treatments targeting pruritus in liver diseases is relatively underserved and volixibat’s early results could generate excitement in the medical community, potentially driving adoption upon approval.
For investors, the key points to watch will include final trial outcomes, potential FDA feedback and any updates on commercialization strategies. The positive interim results are encouraging, but the company’s ability to navigate regulatory hurdles and effectively market the drug will be important for long-term success.
- VANTAGE PBC interim analysis shows 3.8 point reduction from baseline and 2.3 point placebo-adjusted (p=0.0026) reduction in primary endpoint of pruritus
- VISTAS PSC interim analysis exceeds efficacy threshold for study continuation
- Mirum to host conference call to discuss analyses, today, June 17 at 8:30 a.m. ET/5:30 a.m. PT
Interim results from the VANTAGE study evaluating volixibat in patients with PBC demonstrated a statistically significant (-3.82, p<0.0001) improvement in pruritus for volixibat and a placebo-adjusted difference of -2.32 points in the primary endpoint, p=0.0026, as measured by the Adult ItchRO scale.
No new safety signals were observed, and adverse events were similar between the 20 mg and 80 mg treatment groups. The most common adverse event was diarrhea (
Adult ItchRO Change from Baseline
Mean change in Adult ItchRO score* |
20 mg (n=10) |
80 mg (n=10) |
20+80 mg (n=20) |
PBO (n=10) |
LSMean (SE) P-value |
-3.84 (0.609) <0.0001 |
-3.79 (0.564) <0.0001 |
-3.82 (0.414) <0.0001 |
-1.50 (0.585) 0.0149
|
Difference between VLX and PBO P-value |
-2.34 0.0090 |
-2.29 0.0075 |
-2.32 0.0026 |
|
*Adult ItchRO is a 0-10 numerical rating scale; MMRM weekly averaged worst daily itch score, assessed over weeks 17-28 of the treatment period. |
||||
Based on these results, the VANTAGE PBC trial will continue with a volixibat dose of 20 mg twice daily.
Concurrently, the interim analysis for the VISTAS PSC study was conducted and the independent data review committee recommended that the study continue with the selected volixibat dose of 20 mg twice daily, with no changes to the study. The criteria for continuation included safety as well as a predefined threshold for efficacy. The sponsor and investigators are blinded to the interim results and analysis.
“The interim data from the VANTAGE study provide outstanding results in relation to what has been shown for treatment of pruritus in PBC,” said Joanne Quan, MD, chief medical officer at Mirum. “With both VISTAS and VANTAGE advancing to enroll their confirmatory portions, we are excited about volixibat as a potential future option to help patients overcome one of the most prevalent and burdensome symptoms of these rare liver diseases.”
“The results of the interim analyses are very impressive as they confirm the potential of volixibat in targeting bile acids in PBC and PSC,” said Kris Kowdley, MD,
“The symptomatic burden in PBC is significant and often an underappreciated aspect of this disease. Both itch and fatigue are devastating hallmarks of PBC that can significantly decrease quality of life,” said Carol Roberts, president of the PBCers Organization. “It is incredibly encouraging for PBC patients to see such promising results with volixibat.”
Conference Call to Discuss Interim Analysis
Mirum will be hosting a conference call to discuss the interim analyses from VISTAS and VANTAGE today, Monday, June 17 at 8:30 a.m. ET/5:30 a.m. PT. Join the call by dialing (404) 975-4839 (local/int’l) or (833) 470-1428 (toll-free) and using the access code: 205511. You may also access the webcast through Mirum’s Investor Relations website.
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. Phase 1 and Phase 2 studies of volixibat demonstrated on-target fecal bile acid excretion, a pharmacodynamic marker of ASBT inhibition, in addition to decreases in LDL cholesterol and increases in 7αC4 which are markers of bile acid synthesis. Volixibat has been evaluated in more than 400 individuals across multiple clinical trials. The most common adverse events reported were mild to moderate gastrointestinal events observed in the volixibat groups. Volixibat is currently being evaluated in Phase 2b studies for primary sclerosing cholangitis (VISTAS study), and primary biliary cholangitis (VANTAGE study).
About Mirum Pharmaceuticals, Inc.
Mirum Pharmaceuticals, Inc. is a biopharmaceutical company dedicated to transforming the treatment of rare diseases affecting children and adults. Mirum has three approved medications: LIVMARLI® (maralixibat) oral solution, CHOLBAM® (cholic acid) capsules, and CHENODAL® (chenodiol) tablets.
LIVMARLI, an IBAT inhibitor, is approved for the treatment of two rare liver diseases affecting children and adults. It is approved for the treatment of cholestatic pruritus in patients with Alagille syndrome in the
Mirum’s late-stage pipeline includes two investigational treatments for debilitating liver diseases. Volixibat, an IBAT inhibitor, is being evaluated in two potentially registrational studies including the Phase 2b VISTAS study for primary sclerosing cholangitis and Phase 2b VANTAGE study for primary biliary cholangitis. Lastly, CHENODAL has been evaluated in a Phase 3 clinical study, RESTORE, to treat patients with CTX, with positive topline results reported in 2023.
To learn more about Mirum, visit mirumpharma.com and follow Mirum on Facebook, LinkedIn, Instagram and Twitter (X).
LIVMARLI® (maralixibat) Oral Solution
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 Alagille syndrome 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 Alagille syndrome 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
Forward-Looking Statements
This press release contains “forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Such forward-looking statements include those regarding the clinical potential and regulatory process for volixibat, the ability for volixibat to impact bile acids or pruritus in patients with PSC or PBC, and the effectiveness of volixibat in a real-world population, if ever approved by the FDA. 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 “will,” “could,” “would,” “potential” 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 associated with Mirum’s business in general, the impact of the COVID-19 pandemic, and the other risks described in Mirum’s filings with the Securities and Exchange Commission. 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. A further description of risks and uncertainties can be found in Mirum’s Annual Report on Form 10-K for the fiscal year ended December 31, 2023 and in its subsequent reports on Form 10-Q, including in the sections thereof captioned “Risk Factors,” as well as in its subsequent reports on Form 8-K, all of which are filed with the
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Media Contact:
Erin Murphy
media@mirumpharma.com
Investor Contact:
Andrew McKibben
ir@mirumpharma.com
Source: Mirum Pharmaceuticals, Inc.
FAQ
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