Mirum Pharmaceuticals, Inc. (Nasdaq: MIRM) has reported positive topline results from its Phase 3 EXPAND trial, demonstrating that LIVMARLI (maralixibat) significantly reduced cholestatic pruritus in children with ultra-rare cholestatic liver diseases, including biliary atresia. Announced on October 12, 2026, the randomized study met its primary endpoint with a 0.98-point placebo-adjusted improvement in itch severity (p=0.0004), while all five prespecified secondary endpoints also achieved statistical significance.
The study enrolled 52 patients, including 46 children and six adults, and evaluated maralixibat against placebo over a 20-week double-blind treatment period. Patients receiving LIVMARLI experienced a 1.81-point improvement from baseline in the observer-reported itch severity score, compared with a 0.83-point improvement among placebo recipients. The treatment also produced a 70.1% reduction from baseline in serum bile acids, compared with 3.5% for placebo, yielding a model-estimated relative treatment effect of 69.0%.
The results are particularly relevant to biliary atresia, a serious childhood liver disease characterized by damaged or obstructed bile ducts and progressive impairment of bile flow. In patients with biliary atresia who retained their native liver, LIVMARLI achieved a 1.15-point placebo-adjusted improvement in itch severity and a model-estimated 73.1% treatment effect on serum bile acids. Both findings were statistically significant, strengthening the evidence supporting further investigation of maralixibat in a population with limited approved pharmacological options for cholestatic itching.
Mirum plans to submit a supplemental New Drug Application to the U.S. Food and Drug Administration during the first half of 2027, seeking to extend LIVMARLI’s existing use into additional rare cholestatic conditions. The medicine is already approved for cholestatic pruritus associated with Alagille syndrome and progressive familial intrahepatic cholestasis, but it is not currently approved for biliary atresia. The EXPAND results therefore represent a potential label-expansion milestone rather than a new regulatory authorization.
How significant was LIVMARLI’s improvement in cholestatic pruritus during the EXPAND trial?
The primary endpoint evaluated changes in the average worst-daily Itch Reported Outcome observer score, known as ItchRO(Obs), between baseline and the average of Weeks 13 through 20. The assessment uses a numerical scale ranging from zero to four, providing a structured measure of itch severity based on observations of affected children. The primary analysis included 46 pediatric patients, with 22 receiving maralixibat and 24 receiving placebo.
According to Mirum, patients receiving LIVMARLI experienced an adjusted mean improvement of 1.81 points, compared with 0.83 points in the placebo group. The resulting treatment difference of 0.98 points achieved statistical significance at p=0.0004. Because the scale contains only five possible severity levels, an improvement approaching one additional point over placebo may represent a meaningful change in symptoms, although individual responder outcomes and the clinical significance across different baseline severity levels will require further evaluation.
The placebo response deserves consideration because patients receiving inactive treatment also experienced measurable improvement during the study. This is not unusual in trials involving symptoms that vary over time or depend on observer assessments. The randomized, double-blind design helps establish that the additional improvement seen with maralixibat was unlikely to arise solely from expectations or ordinary symptom fluctuations, but the full dataset will be needed to assess the consistency of benefits between individuals.
The first secondary endpoint provided additional support for the primary result. Patients receiving LIVMARLI experienced pruritus improvement on 86.0% of assessed days during Weeks 13 through 20, compared with 49.1% among placebo recipients, representing a difference of 36.9 percentage points (p=0.0008). In this analysis, improvement meant a worst-daily score of one or less, or a reduction of at least one point from baseline.
This measurement adds an important dimension because reductions in average severity do not necessarily reveal how consistently symptoms remain controlled. A patient experiencing fewer severely affected days may obtain practical benefits that differ from those associated with occasional episodes of substantial relief. Nevertheless, the announcement does not provide detailed sleep, caregiver burden or quality-of-life outcomes, so improvements in those domains should not be assumed from the itch scores alone.
Why are the biliary atresia subgroup results particularly important for LIVMARLI’s development?
The biliary atresia subgroup provides some of the most relevant evidence for Mirum’s proposed expansion strategy. The prespecified analysis included 25 patients with biliary atresia who retained their native liver, comprising 11 receiving maralixibat and 14 receiving placebo. Their inclusion matters because biliary atresia involves a different underlying disease mechanism from the genetic cholestatic disorders for which LIVMARLI is already authorized.
In this subgroup, LIVMARLI produced a 2.16-point improvement from baseline in itch severity, compared with a 1.01-point improvement for placebo. The placebo-adjusted difference was 1.15 points, with statistical significance at p=0.0002. The magnitude of improvement was numerically greater than in the overall pediatric analysis, suggesting that meaningful symptom relief may be achievable in selected patients with biliary atresia.
The findings were supported by an additional measure of treatment consistency. Patients receiving maralixibat experienced pruritus improvement on 96.4% of assessed days, compared with 52.2% among placebo recipients, representing a 44.1-percentage-point difference (p=0.0045). These results suggest that the observed benefit was not confined to a single assessment or isolated period within the later weeks of the study.
Serum bile acid measurements also favoured active treatment in this subgroup. Mirum reported a 75.5% reduction from baseline among patients receiving LIVMARLI, compared with a 9.0% reduction for placebo, corresponding to a model-estimated 73.1% relative treatment effect (p less than 0.0001). The treatment effect was derived from logarithmically transformed data and should not be confused with a simple subtraction of the two percentage changes.
Although the three biliary atresia secondary endpoints were prespecified and statistically significant, the analysis involved only 25 patients. This is understandable in an ultra-rare disease but still limits the precision and generalizability of the findings. Further information about patient age, previous surgery, liver function and other baseline characteristics will help clarify the populations most likely to benefit.
Could reducing serum bile acids change the course of biliary atresia and other cholestatic liver diseases?
LIVMARLI is an orally administered inhibitor of the ileal bile acid transporter, commonly called IBAT. By blocking the reabsorption of bile acids from the terminal ileum, the medicine increases their elimination through the gastrointestinal tract and reduces their return to the liver. This mechanism is intended to decrease circulating bile acid concentrations and alleviate cholestatic itching associated with impaired bile flow.
The EXPAND trial demonstrated a strong biochemical effect, with a 70.1% reduction in serum bile acids among maralixibat-treated patients compared with 3.5% in the placebo group. The reported model-estimated treatment effect was 69.0%, reaching statistical significance at p less than 0.0001. The results provide evidence that LIVMARLI affected its intended biological pathway in a population extending beyond its currently approved indications.
However, bile acid reduction and relief from itching should not be equated with demonstrated prevention of liver failure or avoidance of transplantation. Cholestatic liver diseases involve complex pathological processes, including inflammation, fibrosis and progressive tissue injury, which may not be fully reversed by reducing intestinal bile acid reabsorption. The October disclosure does not establish improvements in native-liver survival, transplant-free survival or long-term disease progression.
This distinction is particularly important in biliary atresia because the condition usually requires early surgical intervention. The Kasai portoenterostomy procedure attempts to restore bile drainage by connecting the liver directly to the intestine, but some children continue to experience progressive liver disease despite surgery. Liver transplantation remains an important treatment option when disease progression or complications cannot be adequately controlled.
For these patients, a medicine that reduces severe itching could still offer meaningful benefits even without demonstrating reversal of the underlying disorder. Persistent cholestatic pruritus can interfere with sleep, comfort and everyday functioning, placing substantial burdens on children and their caregivers. The strongest supported conclusion from EXPAND is that maralixibat improved measured itch outcomes over 20 weeks, accompanied by reduced serum bile acids.
What do the Phase 3 EXPAND safety findings reveal about diarrhoea and liver-related risks?
Mirum reported that the overall safety profile of LIVMARLI in EXPAND was consistent with previous clinical experience and that no new safety signals were identified during the 20-week double-blind period. Treatment-emergent adverse events occurred in 96.0% of patients receiving maralixibat and 96.3% receiving placebo. Grade 3 or higher events occurred in 24.0% and 22.2% of patients, respectively, while serious treatment-emergent adverse events were reported in 20.0% and 18.5%.
The most prominent difference involved diarrhoea, which occurred in 64.0% of maralixibat recipients compared with 11.1% of placebo recipients. This represented 16 of 25 treated patients compared with three of 27 receiving placebo, an absolute difference of approximately 53 percentage points. The imbalance is clinically relevant because gastrointestinal tolerability can affect treatment continuation, hydration and nutritional management, particularly among children with underlying liver disease.
Abdominal pain occurred in 20.0% of patients receiving maralixibat compared with 14.8% receiving placebo. Increased alanine aminotransferase was reported in 8.0% and 3.7%, respectively, although these small event counts limit comparative interpretation. One patient receiving LIVMARLI discontinued the study prematurely because of a treatment-emergent adverse event, while no such discontinuations were reported in the placebo group.
Five patients in each treatment group experienced serious adverse events. Events among maralixibat-treated patients included pneumonia, fever, large intestine infection, acute kidney injury and viral infection with bronchiolitis, none of which investigators considered related to the study drug. No deaths were reported during the double-blind period.
The existing United States prescribing information remains important when interpreting these findings. LIVMARLI is associated with warnings concerning drug-induced liver injury, gastrointestinal adverse reactions and fat-soluble vitamin deficiency. Its established safety information includes serious liver-related complications reported in earlier progressive familial intrahepatic cholestasis studies, including cases associated with transplantation and death.
The absence of a new safety signal in EXPAND therefore does not eliminate known risks or establish equivalent long-term tolerability across all cholestatic conditions. The randomized safety population contained only 52 patients, and the controlled observation period lasted 20 weeks. Regulators will need to examine the complete safety package, including the implications of diarrhoea and liver monitoring in patients with biliary atresia and other uncommon cholestatic diseases.
How would a successful FDA label expansion change LIVMARLI’s approved patient population?
LIVMARLI’s existing United States approvals provide an established regulatory and commercial foundation for the proposed expansion. The medicine is authorized for cholestatic pruritus in patients aged three months and older with Alagille syndrome and in patients aged 12 months and older with progressive familial intrahepatic cholestasis. The approved indications have different age thresholds and dosing requirements, reflecting separate clinical development programmes.
EXPAND evaluated patients aged six months and older with additional ultra-rare cholestatic liver diseases, including biliary atresia. A supplemental New Drug Application could allow Mirum to seek an extension of its existing label to cover selected additional conditions, provided the FDA determines that the submitted evidence supports the proposed indication. The final scope could depend on the enrolled populations, efficacy analyses, dosing information and safety findings.
The proposed submission is expected during the first half of 2027, but Mirum has not announced that an application has already been filed or accepted for review. A positive Phase 3 result strengthens the evidence supporting regulatory development without guaranteeing authorization. The FDA may also examine whether the heterogeneous conditions included in EXPAND support a common indication or require more specific labeling language.
The distinction between the overall trial population and its pediatric primary analysis will be relevant to that assessment. Although EXPAND enrolled six adults, the primary itch efficacy result was derived from 46 pediatric participants. The full regulatory package will need to clarify how evidence can be applied to different age groups and disease categories beyond those directly represented in the primary analysis.
Mirum has received orphan drug designation for maralixibat in biliary atresia, which provides a separate regulatory development incentive. However, orphan designation is not an approval and does not establish clinical efficacy. The potential new indication remains dependent on successful FDA review of the complete EXPAND evidence.
What could the EXPAND results mean for Mirum Pharmaceuticals’ commercial growth and investor sentiment?
LIVMARLI is already a significant contributor to Mirum Pharmaceuticals’ revenue, making a possible label expansion commercially meaningful beyond the immediate clinical announcement. The company reported LIVMARLI net product sales of $128.7 million during the second quarter of 2026, compared with $88.2 million in the corresponding period of 2025. This represented approximately 46% year-on-year growth, driven primarily by stronger United States demand across its existing Alagille syndrome and progressive familial intrahepatic cholestasis indications.
For the first six months of 2026, LIVMARLI generated $242.5 million in net sales, compared with $161.4 million a year earlier. The product accounted for approximately 72% of Mirum’s $336.1 million in total first-half net product sales, demonstrating its importance within the company’s commercial portfolio. Those figures also show that LIVMARLI already has an established market presence rather than being a medicine whose commercial value depends entirely on its next regulatory decision.
A potential expansion into biliary atresia and other rare cholestatic conditions could allow Mirum to use its existing specialist commercial infrastructure to reach additional eligible patients. The same physician networks, pediatric hepatology centres and reimbursement channels involved in rare liver disease treatment may provide useful foundations for future adoption. However, the actual commercial opportunity will depend on the final approved population, diagnosis rates, payer coverage and the number of patients suitable for treatment.
The company has not disclosed a new addressable patient estimate or revenue forecast specifically attributable to the EXPAND findings. It would therefore be premature to calculate incremental sales based on the total prevalence of biliary atresia or assume that every patient with persistent cholestasis would be eligible. The trial focused on a defined patient population experiencing cholestatic pruritus, and any commercial use must remain consistent with the eventual authorized indication.
Mirum’s broader corporate position has also evolved during 2026, including the September FDA approval of Atebrioz (zilurgisertib) for fibrodysplasia ossificans progressiva in patients aged 12 years and older. This adds another approved rare-disease medicine alongside LIVMARLI and the company’s bile-acid-related treatment portfolio. Nevertheless, the EXPAND result is most directly relevant to strengthening the existing LIVMARLI franchise rather than creating a completely separate commercial business.
Mirum shares closed at $86.01 on October 9, before the EXPAND announcement, after gaining approximately 5.7% during that session. The positive topline results initially attracted favourable premarket attention on October 12, although intraday trading was volatile and should not be treated as a definitive assessment of the programme’s value. The clinical result reduces an important source of development uncertainty, but investors still face questions about regulatory approval, the size of the eligible market and the durability of the treatment’s competitive position.
What will determine whether EXPAND’s positive results translate into a broader LIVMARLI approval?
The next major milestone is Mirum’s planned supplemental New Drug Application during the first half of 2027. Before that filing, the company will need to complete the regulatory evidence package supporting efficacy, safety and proposed dosing across the intended patient population. The detailed Phase 3 results will be important for assessing consistency of treatment response, baseline disease characteristics and the clinical significance of improvements beyond the headline averages.
The strength of the study lies in its randomized, double-blind, placebo-controlled design and the consistency of statistically significant findings across symptom and biochemical assessments. The inclusion of prespecified biliary atresia analyses provides additional support for a particularly important patient group. However, small subgroup sizes, the short controlled observation period and the absence of demonstrated long-term liver outcomes remain relevant limitations.
Clinicians will be interested in whether the improvements in itching are sustained with longer treatment and whether gastrointestinal adverse events can be managed without compromising nutritional status or treatment continuation. Regulators will need to assess how the safety profile established in existing indications translates to patients with different underlying liver conditions. Commercial adoption will ultimately require appropriate coverage, specialist prescribing and monitoring arrangements.
For Mirum Pharmaceuticals, EXPAND represents another successful clinical development milestone for an already commercialized medicine. The trial demonstrated a statistically significant improvement in its primary itch endpoint, confirmed supportive changes in serum bile acids and produced consistent results in a prespecified biliary atresia subgroup. The remaining challenge is to convert those findings into an appropriately defined regulatory indication while preserving a favourable benefit-risk profile in a particularly vulnerable patient population.
The October 2026 findings provide a credible basis for seeking broader treatment access, but they do not establish that LIVMARLI changes the long-term course of biliary atresia or prevents liver transplantation. Its clearest demonstrated benefit is relief of cholestatic pruritus over the controlled study period, supported by measurable biochemical activity. Whether that evidence leads to an expanded United States label will depend on the FDA’s review of the complete EXPAND dataset and the safety requirements applicable to the proposed new patient groups.
