Rare liver disease wins mount as Mirum’s PFIC trial meets endpoint

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Abdomen scan

Rare liver disease wins mount as Mirum’s PFIC trial meets endpoint

Published: Oct 25, 2022

By Tristan Manalac


Therapeutic wins for rare liver diseases are becoming common of late as Mirum Pharmaceuticals‘ Livmarli (maralixibat) oral solution met its primary endpoint in a Phase III study in progressive familial intrahepatic cholestasis (PFIC). 

This comes just two weeks after competitor Albireo announced a similar victory.

In 31 patients with PFIC subtype 2, treatment with Livmarli led to a 1.7-point decrease in scores in the caregiver-completed ItchRO, a tool used to evaluate the impact of itching in pediatric cases of cholestasis, Mirum announced Monday.

Scores dropped by 0.6 points in the placebo group. The 1-point treatment difference was statistically significant, with a p-value of 0.0098.

Livmarli also resulted in a significantly greater reduction in serum bile acid levels compared to placebo.

PFIC is a rare, progressive, genetic liver disorder characterized by bile build-up, which leads to liver damage. An important symptom of PFIC is severe itching (pruritus), which compromises quality of life and often interferes with sleep.

On Monday, Chris Peetz, president and chief executive officer of Mirum, told investors the company “will move rapidly towards regulatory filings for PFIC.”  

The Phase III MARCH study is a randomized, quadruple-masked and parallel trial enrolling 93 patients aged one to 17 with a broad range of PFIC subtypes. 

Mirum also evaluated Livmarli in all 64 PFIC patients, including those with other subtypes. The drug demonstrated a 1.2-point treatment effect compared with placebo, indicative of significantly better itch control.

Livmarli’s safety was assessed in the full study sample, including supplemental patients who had undergone surgery before enrolment and those who had truncating mutations. All Livmarli-treated participants developed treatment-emergent adverse events, of which three and five were deemed to be severe and serious, respectively.

One Livmarli patient dropped out of the study due to the drug’s side effects, while no deaths linked to toxicities were reported. Diarrhea was the most common adverse event.

During the investor call, Pamela Vig, Ph.D., head of R&D at Mirum, said the consistent pruritus treatment effect in the full study sample “is a remarkable result given the heterogeneity of the population.

Vig called the overall magnitude of serum bile acid and pruritus response observed across all cohorts “unprecedented.”

The proportion of patients who achieved the serum bile acid threshold, which is predictive of transplant-free survival, has gone from one-third to over half, she added. 

Albireo’s Alagille Syndrome Win

Earlier this month, Albireo posted positive Phase III results for its Bylvay in Alagille syndrome, a genetic disease that affects not only the liver but also other organs, including the eyes, heart and kidneys.

As in the case of PFIC, a major symptom of Alagille syndrome is severe itching.

Similar to Mirum’s Livmarli, patients treated with Blyvay saw a rapid and sustained drop in symptoms of pruritus, as well as in bile acid levels. Bylvay has already been approved by the FDA for PFIC. Meanwhile, Livmarli remains the only FDA-approved drug for pruritus in Alagille syndrome.

Source: BioSpace