When Madrigal Prescription drugs achieved a first-in-disease approval for the MASH remedy Rezdiffra this 12 months, the corporate had a transparent head begin in an rising market that’s turn out to be a primary goal for drugmakers.
Regardless of being the one pharma with an authorized MASH drug, Madrigal’s entry into the house has additionally created a possible benefit for different corporations searching for a means in.
“Madrigal is doing loads of work for us,” mentioned Frederic Cren, CEO of Inventiva Pharma, which has its personal oral MASH drug candidate lanifibranor in part 3 testing. “They’re educating physicians. They’re making the final inhabitants conscious [of] the severity of this illness, and once we arrive with what we expect might be a extra efficacious drug, the market might be massive and open to a brand new oral drug.”
Inventiva’s lanifibranor is a PPAR agonist designed to induce anti-fibrotic, anti-inflammatory and metabolic modifications in MASH sufferers. With investor enthusiasm excessive within the cardiometabolic house, Inventiva raised $367 million in an October financing spherical.
Simply how massive is the MASH market?
Rezdiffra gross sales topped $62 million throughout the third quarter of 2024, nicely above analysts’ expectations of $36 million for the quarter. Plus, Madrigal mentioned it was forward in its targets for prescribing protection.
Throughout the event panorama, a number of different pharmas and biotechs have MASH medication within the clinic, together with 89bio, Akero Therapeutics and Galectin Therapeutics.
However off within the distance, one other class of remedies await their shot at MASH: GLP-1s.
GLP-1s for MASH
Novo Nordisk, the most important vendor within the GLP-1 market, introduced earlier this month it was looking for regulatory approval for semaglutide — the lively ingredient in its blockbuster weight reduction and diabetes medication Ozempic and Wegovy — in MASH. The information got here with constructive part 3 trial outcomes displaying MASH sufferers with average to superior liver fibrosis noticed “enchancment in liver fibrosis with no worsening of steatohepatitis,” or fats buildup within the liver, the corporate mentioned.
GLP-1s are among the many bestselling medication previously few years, and their affect within the MASH market is also substantial. Eli Lilly is in part 2 testing for MASH indications for tirzepatide, the ingredient in its GLP-1 blockbusters Mounjaro and Zepbound.
Nevertheless, Cren isn’t nervous the GLP-1s may eclipse market alternatives. As a substitute, he views their affect as probably deepening the marketplace for Inventiva’s lanifibranor and creating a chance for MASH medication for use alongside GLP-1s.
“It is nice information for sufferers, but in addition nice information for us, as a result of it implies that massive pharma might be more and more extra ,” Cren mentioned. “However [GLP-1s] will have to be mixed with one other remedy that may present extra efficacy and particularly a direct exercise on fibrosis.”
Cren additionally believes GLP-1s might be much less appropriate for long-term use as a consequence of their disagreeable gastrointestinal uncomfortable side effects. Madrigal additionally identified in its third-quarter earnings presentation that 70% of semaglutide customers discontinued remedy after 12 months, underscoring the adherence problem.
Market differentiation
Even with Rezdiffra’s success, there’s probably loads of room out there for opponents. Like GLP-1s, Rezdiffra has potential GI uncomfortable side effects, which may affect its uptake, in response to an April survey of gastroenterologists. Moreover, there could also be some sufferers with average to extreme liver fibrosis who don’t reply to Rezdiffra, the survey mentioned.
One “key characteristic” of lanifibranor is its potential to cut back insulin resistance, as many sufferers with MASH even have kind 2 diabetes and will have bother controlling their blood sugar, mentioned Cren. The drug additionally improves fatty liver. In Inventiva’s part 2 trial, 83% of sufferers handled with lanifibranor confirmed “a discount better or equal to 30% of their hepatic fats.” Plus, sufferers noticed reductions in fibrosis biomarkers. Inventiva can also be betting that lanifibranor can rise above different PPAR agonists by concentrating on three PPAR isoforms moderately than only one or two.
“It is a advanced illness, so that you want a drug that in the end prevents a affected person from changing into cirrhotic,” Cren mentioned. “You need a drug that may regress your degree of fibrosis — [it’s] actually what everyone’s searching for.”
The corporate is about 90% enrolled with its practically 1,000-patient part 3 trial, which can run for 18 months, in response to Cren. But it surely hasn’t been all clean crusing for Inventiva, which briefly paused enrollment of its part 3 examine earlier this 12 months after discovering elevated enzymes in a affected person. The pharma plans to publish knowledge from the examine within the second half of 2026, Cren mentioned.
