The American Association for the Study of Liver Disease (AASLD) held its annual Liver Meeting from November 4-7, 2022 in Washington, D.C. During the meeting, Mirum Pharmaceuticals shared two late-breaker presentations on data from the MARCH-PFIC and RISE studies. From the RISE study, Mirum shared information on LIVMARLI for pediatric patients (aged 2 months or older) with Alagille syndrome; from the MARCH-PFIC study, the company shared safety and efficacy data on LIVMARLI for progressive familial intrahepatic cholestasis (PFIC).
Mirum Pharmaceuticals is committed to making a change in the realm of rare liver diseases – and the data shows how its therapies are helping to improve patient outcomes.
Recently, I sat down with Mirum’s CEO Chris Peetz to discuss the findings from the MARCH-PFIC study, the challenges and rewards of drug development and medical research, and the importance of patient-centricity throughout this process.
About Chris Peetz
Chris Peetz is the President, Chief Executive Officer (CEO), and Co-Founder of Mirum Pharmaceuticals, a biopharmaceutical company that is working to develop transformative therapies for rare liver diseases.
Chris Peetz earned his B.S.B.A. in Finance, International Business and French from Washington University in St. Louis before pursuing, and achieving, his M.B.A. from Stanford Graduate School of Business. He shares:
Originally, I have a background in finance and business. I always toyed with the idea of studying the sciences academically, and dabbled with lab research, but fell back into the finance realm. I’m a bit of a self-professed spreadsheet nerd. However, after starting my career, I found myself drawn back to the life sciences.
Chris jumped into biotechnology in the Bay Area, where he’s remained for about eighteen years. He has worked at a number of different drug development companies, including Onyx Pharmaceuticals, Jennerex Biotherapeutics, Tobira, and Flashlight Therapeutics, explaining:
This is actually what pushed me into the direction of rare liver diseases. At first, I was working in oncology. I was fascinated when I started doing work in liver cancer, which led to liver fibrosis. Suddenly, I was doing a deep dive into the world of liver diseases. It’s not always straightforward to develop a medicine for an organ in the middle of the body. But that’s what makes the process so intriguing.
The Journey to Mirum
From May 2014 through December 2016, Chris worked as Chief Financial Officer (CFO) and Head of Corporate Development at Tobira, a company later acquired by Allergan plc. During his time at Tobira, Chris was working in the realm of liver fibrosis. He explains:
I got the chance to work with some of our original investors. We wanted to find promising new medications for liver diseases and even launch a new company around it. When we formed Mirum, we found these two fantastic products – LIVMARLI and volixibat – that were not being given the right attention at other companies.
Mike Grey, one of Mirum’s co-founders who now sits as Chairman on the Board of Directors, had been involved in the Alagille syndrome space and was very familiar with the needs of the community through his work with the the Alagille Syndrome Alliance (ALGSA). When he went to events, he noticed that children using LIVMARLI were experiencing benefits while on the medication. Chris explains:
When we formed Mirum, we learned that LIVMARLI was going to be discontinued. But we saw the tremendous impact it was having in clinical settings and knew we wanted to build a company around that. So hearing that this drug would be deprioritized encouraged us to jump right in. We had a huge advantage because the data that had already been generated was so striking. There were small studies into Alagille syndrome and progressive familial intrahepatic cholestasis, or PFIC, but the patients had transformational responses. Pruritus resolved. Bile acids were lowered or normalized. Patients had growth spurts and now, several years in, are still living transplant-free.
LIVMARLI: An Overview
LIVMARLI (maralixibat) oral solution is an ileal bile acid transporter (IBAT) inhibitor that reduces serum bile acid levels in the body. The medicine prevents and interrupts bile acids from returning to the liver while also increasing bile acid excretion through feces. In doing so, the therapy helps to reduce pruritus (extreme itchiness) caused by high serum bile acid levels.
When Mirum first formed, the team knew that they had a very relevant medicine that targeted bile acids. So they jumped right into a few broad studies to better understand the drug and its effects. In June 2020, Phase 2 clinical data on LIVMARLI demonstrated a five-year transplant-free survival period for pediatric patients with PFIC.
The data in Alagille syndrome was already robust. Chris shares:
We spoke with the FDA and asked if we should submit a New Drug Application since it was clear that the drug had a meaningful impact for patients. The FDA agreed and we would then work towards approval. That set us up for building out the commercial function and actually working to get this medication into the hands of patients in the United States.
In September 2021, the FDA approved LIVMARLI for the treatment of cholestatic pruritus in pediatric patients aged 1+ with Alagille syndrome. It is the first approved treatment for this indication. More recently, in October 2022, LIVMARLI received a positive CHMP opinion for LIVMARLI in pediatric patients aged 2 months+. Chris explains:
The CHMP opinion is the major step in working towards European approval. We’re very excited to have reached this point and are doing a lot of work to prepare for the European launch of LIVMARLI. This took a few extra steps. The FDA saw our data, granted us Breakthrough Therapy designation, and accelerated us in the submission process. In Europe, they asked for additional analyses such as longer-term follow-up and the potential to impact longer-term outcomes.
To achieve this, Mirum began working with Dr. Binita Kamath, a hepatologist at SickKids in Toronto and one of the leading academic researchers in Alagille syndrome. Dr. Kamath and her team established the largest ever dataset tracking how children with Alagille syndrome progress over time. Next, she ran an analysis of patients taking LIVMARLI, versus those not taking LIVMARLI, over a five-year period. As Chris explains:
We saw a significant improvement in transplant rates for children taking LIVMARLI compared to matched children in the database. This data was a key part of the conversation with the EMA which let them grant us this positive opinion. We should hear more about EC approval within the next sixty days.
LIVMARLI is also approved for use in Israel as well and will be distributed by Neopharm, a Mirum partner and local distributor. Chris shares that working with local distributors on a global scale will help them provide important therapies to those in need as broadly as possible.
Join us in Part 2, where Chris discusses the development of LIVMARLI for PFIC, the challenges and rewards of drug development, and how Mirum aims to maintain patient-centricity in its work.
