Before you read on, make sure to check out Part 1 of our interview. In Part 1, Chris Peetz discusses his background, why he joined Mirum, and the process of evaluating LIVMARLI for patients with progressive familial intrahepatic cholestasis (PFIC). Today, he unpacks positive topline data from the Phase 3 MARCH-PFIC study, talks about the challenges and rewards of drug development, and explains Mirum’s patient-centricity.

Evaluating LIVMARLI for PFIC

In late October 2022, Mirum shared positive topline data from the Phase 3 MARCH-PFIC study evaluating the safety, efficacy, and tolerability of LIVMARLI for progressive familial intrahepatic cholestasis (PFIC), a rare inherited condition which causes progressive liver disease. The MARCH trial is the largest PFIC study ever conducted. Altogether, 93 patients between the ages of one to seventeen years old enrolled.

During the trial, patients received 570 µg/kg twice per day of LIVMARLI. The study met its primary endpoint (p=0.0098) and its secondary endpoints with statistical significance. Findings from the study highlight that:

• LIVMARLI significantly improved pruritus severity in patients with PFIC2 (p=0.0098).
• The medication also reduced serum bile acid levels and itch across all PFIC types.
• In the All-PFIC cohort, more than 60% of patients saw reduced itch and more than 50% had serum bile acid reductions.
• LIVMARLI also improved bilirubin and growth in patients versus placebo.
• The most common adverse reaction was diarrhea, but was generally mild with no severe cases, and transient with a median duration of 5.5 days. Only 1 patient had a treatment emergent adverse event of mild diarrhea that led to discontinuation.

Learn more about the study data here.

The Challenges and Rewards of Drug Development

As excited as Chris is to see some of the findings coming out of these studies, getting to that point is not always easy. In fact, one of the biggest challenges of medical research and drug development in the rare disease field is the effort it takes to enroll enough patients. As Chris explains:

“To enroll a study, you have to do a lot of legwork and be active in many different countries. The more rare the disease is, the more you have to search. The more clinical trials you have to enroll and set up and interact with. For example, the MARCH study is global, and it takes work to be that broad and active around the globe.”

Despite the hard work, this process can be extremely rewarding, especially when the team at Mirum is able to see how the drug affects patients. Chris shares:

“These little moments when we see how direct of an impact our drugs have is my absolute favorite part of the job. Recently, at a conference, I met a family whose son has PFIC. The family introduced themselves and talked about how transformational LIVMARLI has been. I saw their son who had, earlier in his life, been on the liver transplant list. Now he had a completely different trajectory. It’s hard to express this more personal side with a clinical trial readout. Everything is in numbers and can sound very dry. But knowing what that number translates to on an individual level is very exciting.”

The Future of Mirum (and How to Maintain a Patient-Centric Focus)

During the course of our interview, Chris really stressed how important it was for Mirum to engage with the patient perspective – and to ensure that the entire drug development and research process was as patient-centric as possible. He explains:

“What we’re trying to do is have relevant, impactful medicine for patients. But to do that, we have to talk to them. We have to listen. We want input on everything from commercial rollout and distribution to study design. It’s a little different for each disease state, but we often reach out to different groups and ask them to look at study design. What would this be like for you as a patient or family member? Any feedback on how we’re setting up study visits? How often do you go to your physician? What is your daily experience like and how can we improve that? Ultimately, we want to ensure that what we’re doing is relevant for those in these communities.”

For example, Mirum recently worked with the mother of a child who has Alagille syndrome. She helped Mirum create a virtual reality experience for healthcare practitioners and physicians on what it’s like to spend a day as a caregiver for a child with Alagille syndrome: a snippet of the doctor’s office, the frustration of finding the right words, stress, and managing sleep for a child whose itch is too intense. Integrating this direct input is powerful and could help physicians better connect with and understand the patient experience.

Moving into the future, Chris explains that Mirum hopes to continue growing and expanding into different disease states. The company is already active in biliary atresia (with data anticipated in the second half of 2023). Mirum is developing and investigating volixibat for a variety of adult cholestatic diseases. Currently, they are enrolling a study for primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC). Chris shares:

“Both of those are cholestatic settings in which the liver has either cholestasis or scarring, and bile acids are elevated similar to the pediatric setting. It can cause fatigue, progressive liver damage, and worsened quality-of-life. We hope to see data that will show volixibat as a way to improve standards-of-care in that setting.”

Additionally, Mirum is exploring the possibility of developing volixibat for intrahepatic cholestasis of pregnancy (ICP), a condition in which pregnant women experience spontaneous cholestasis and pruritus. Ultimately, Chris says:

“Mirum has been able to pull some really great people together and advance research in different fields. We want to help people and provide a better quality-of-life. So, as we move forward, I have one main question: where are some rare disease programs that aren’t getting enough attention and how can we bring that into Mirum?”