CSPC Pharmaceutical Group Ltd.

The European Commission granted conditional marketing authorisation for Madrigal Pharmaceuticals' Rezdiffra (resmetirom), establishing the first approved therapy for metabolic dysfunction-associated steatohepatitis (MASH) in the EU.The once-daily oral thyroid hormone receptor-β agonist — specifically indicated for adults with non-cirrhotic MASH having moderate to advanced liver fibrosis (F2-F3) — is expected to first hit the shelves in Germany in the last quarter, with other countries following suit thereafter. “This approval…marks a historic breakthrough for patients in Europe living with MASH…with no biopsy required to qualify for treatment…and a clear focus on a distinct…population with high unmet need,” explained Madrigal CEO Bill Sibold.Rezdiffra’s EU nod comes more than a year after its FDA approval and closely follows a positive recommendation from the EMA’s Committee for Medicinal Products for Human Use in June. The latest approval is backed by the pivotal Phase III MAESTRO-NASH trial, in which Rezdiffra at 80 mg and 100 mg doses met the dual primary endpoints of MASH resolution and fibrosis reduction versus placebo. Moreover, 91% of patients receiving the 100mg dose demonstrated improvement or stabilisation of liver stiffness at 12 months.Rezdiffra has performed exceptionally well since its US debut, recently posting second-quarter revenues of $212.8 million — up 55% quarter-over-quarter and well above analyst forecasts of $161 million. However, hot on its trail is Novo Nordisk’s GLP-1 Wegovy (semaglutide), which last week clinched an FDA label expansion in MASH. The Danish drugmaker also submitted an application to the EU regulator in February for the same indication. For more, see – Vital Signs: Tracking the MASH queue for GLP-1 agonists.Meanwhile, looking to further bulk up its MASH portfolio, Madrigal in July secured a key deal worth up to $2.1 billion with CSPC Pharmaceutical for rights to an oral GLP-1 receptor agonist and orforglipron derivative, dubbed SYH2086. The company plans to pair it with Rezdiffra as a combination therapy.

Madrigal Pharmaceuticals’ approved MASH drug could be headed for blockbuster status. Rezdiffra, approved in March 2024 as the first-ever treatment for the fatty liver disease, pulled in $212.8 million in sales during the second quarter, surpassing the Wall Street consensus estimate by about $50 million. The figure represents 55% quarter-over-quarter growth after the drug netted $137.3 million in the first three months of 2025. If its growth continues, it will be on pace to generate $1 billion in sales per year. Madrigal’s stock price $MDGL jumped more than 10% in premarket Tuesday trading, but leveled off after the opening bell to a 5% increase. Sensing an opportunity to capitalize on the early momentum, Madrigal executives outlined their plan to develop combination therapies using Rezdiffra and an oral GLP-1 after announcing last week that it will acquire one . The program, called SYH2086 from China-based CSPC Pharmaceutical, is still preclinical but is expected to start a Phase 1 study in the first half of next year. On an investor call Tuesday, Madrigal CEO Bill Sibold emphasized that about a quarter of the 23,000 patients taking Rezdiffra are also using GLP-1s to manage their comorbidities at any given time. He also touted data claiming to show how MASH patients losing about 5% of their weight can help boost Rezdiffra’s anti-fibrotic effects. “There’s clearly a need in this large and under-penetrated market for multiple mechanisms and better combinations to treat this challenging disease,” Sibold said. Analysts peppered the Madrigal team with questions about the GLP-1 combination efforts, given the drug class’ exploding market. They noted Novo Nordisk’s injectable GLP-1 semaglutide is currently under FDA review in MASH, and questioned whether Rezdiffra’s sales might be impacted should an approval come through. Sibold said Madrigal will have to wait to see how things play out with insurers, but the company is planning “for all eventualities.” He also stressed that SYH2086 fits neatly into Madrigal’s strategy because it’s an oral drug and a derivative of Eli Lilly’s orforglipron — also an oral GLP-1. “There are a lot of oral GLP-1s out there, there are a lot of GLP-1s, GGGs , etc. But there’s only one that’s going to be combined with Rezdiffra in this form,” Sibold said. “And that’s how we differentiate in this market.” Last month, Madrigal said it won extended patent coverage for the drug into 2044. In its earnings report, Madrigal noted the patent — which the company says will be issued Tuesday — will cover Rezdiffra until February 2045. The patent will give Madrigal “another protected decade of revenue,” Sibold said.

Madrigal Pharmaceuticals once again reported an expectations-beating quarter for its THR-β selective agonist Rezdiffra (resmetirom), the first drug approved to treat metabolic dysfunction-associated steatohepatitis (MASH). And while competition is incoming, management projected confidence that the entrance of injectable GLP-1s into the MASH space will only be a net positive for Rezdiffra — and thanks to a licensing deal last month, Madrigal is cooking up its own combination strategy.The drugmaker reported second-quarter revenues for Rezdiffra of $212.8 million, up 55% quarter-over-quarter and blowing past analyst estimates of about $161 million. The beat pushed Madrigal's shares up more than 8% on Tuesday. GLP-1 strategyRezdiffra's status as the only MASH medication, however, could change as early as next year. Madrigal is projecting that Novo Nordisk’s GLP-1 agonist semaglutide — which recently hit its mark in a pivotal MASH study — could be launched for the liver disease in March 2026. For more on GLP-1s in MASH, see – Vital Signs: Tracking the MASH queue for GLP-1 agonists.On an investor call to discuss Madrigal's financial report, CEO Bill Sibold was nonplussed by the looming competition — and predicted it could even be a boon for Rezdiffra. Novo Nordisk's "efforts will raise awareness and drive broader screening, diagnosis and treatment. This will ultimately benefit patients, and we expect it will also benefit both as the foundational therapy and match for first line patients and from the high real world discontinuation rate of semaglutide," Sibold said. And while GLP-1s are widely used for obesity and diabetes, he noted that their low adherence rates might prove a bigger drawback in MASH. "Only approximately 30% of patients with obesity remain on the medicine after one year," Sibold said, referring to semaglutide. "This is especially relevant in MASH, where we're talking about a 72 week efficacy endpoint for a progressive chronic disease like MASH. Providers want a medicine that patients will stay on, and one that they can administer easily without a titration schedule. And that's where Rezdiffra stands out."Tolerability is also key to Madrigal's new combination strategy for Rezdiffra. Last week, the company paid $120 million upfront to license SYH2086, an oral GLP-1 receptor agonist and orforglipron derivative, from Chinese firm CSPC Pharmaceutical. It expects to start a clinical study of the new programme in the first half of next year.According to Sibold, the company has shown that 5% weight loss can increase Rezdiffra's anti-fibrotic effect, and so Madrigal was looking for a candidate that could achieve that level of weight loss without compromising on tolerability."We are looking to develop a chronic therapy for a chronic disease with Rezdiffra as the foundation. We want to optimise the efficacy and tolerability in MASH by balancing the right amount of weight loss from a GLP-1with the fibrosis and lipid reduction of Rezdiffra in a once-daily well-tolerated pill," Sibold said. "We wanted an orforglipron derivative with a favourable stability and pharmacokinetic profile that was amenable to develop as a combination therapy, and of course, an asset that was actionable. We believe that SYH2086 from CSPC Pharma is the right oral GLP-1 asset for our programme. It gives us the opportunity to develop what we believe could become a best-in-disease, well-tolerated oral combination for MASH."More growth driversThe MASH drug is "well on its way to blockbuster status. We can objectively say it stands among the best speciality launches of the last decade," Sibold said on the call. "US Rezdiffra net sales are now annualising at well over $800 million." According to Madrigal, more than 23,000 patients were taking Rezdiffra at the end of the second quarter, an increase of about 6000 compared with the year's first three-month period. FirstWord recently fielded a survey to US physicians that found an urgent need for MASH treatments has been driving the drug's rapid uptake (see – Physician Views Results: Rezdiffra's uptake driven by unmet need, compelling data and diagnostic flexibility).Another source of near-term growth for Rezdiffra could come from its launch in Germany, planned for this half. The European Commission is expected to make a regulatory decision on the drug later this month following a positive recommendation from the Committee for Medicinal Products for Human Use in June. Madrigal is also working towards a label expansion for Rezdiffra into patients with compensated MASH cirrhosis.