Madrigal Pharmaceuticals used its January 12 presentation at the J.P. Morgan Healthcare Conference 2026 to showcase its newly acquired assets from Pfizer – ervogastat and two preclinical assets – as well as outline its vision for dominance in metabolic dysfunction-associated steatohepatitis (MASH) treatment space through leveraging early commercial success. Its professed strategy of pursuing combination therapies while the market remains in its infancy could well result in Madrigal’s brand becoming intrinsically linked to MASH treatment.
The commercial performance of Rezdiffra (resmetirom) provides clear validation for Madrigal’s goals. Rezdiffra reached $287m in net sales during Q3 2025, with annualised revenue exceeding $1bn in the sixth quarter post-launch. The 10,000+ prescribers and more than 29,500 active patients demonstrate genuine and widespread clinical uptake driven by a differentiated once-daily oral profile. These metrics show that Madrigal has successfully identified and addressed unmet need in a historically challenging therapeutic area.
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With the current MASH market at only $180m across two approved products, Madrigal has a narrow window to invest from a position of strength before larger pharmaceutical companies with greater resources enter the space. By securing rights to complementary mechanisms, including Pfizer’s DGAT-2 inhibitor ervogastat and the oral GLP-1 agonist MGL-2086, Madrigal is now positioning itself for a long-term presence in MASH.
Major pharmaceutical companies are already rapidly expanding their involvement in the MASH space, with Roche’s acquisition of 89bio, Novo Nordisk’s acquisition of Akero and GSK’s acquisition of efimosfermin from Boston Pharma. All three assets are FGF21 analogs, belonging to a highly potent, subcutaneously-administered drug class, which boasts impressive MASH resolution and fibrosis improvement data, particularly in longer trials. Once approved, these assets could narrow the market for Rezdiffra, which underlines the importance of combination approaches that could compound Rezdiffra’s effects.
Critically, Madrigal is focusing exclusively on orally administered assets that could potentially be combined with Rezdiffra into a single tablet. This approach would maximise adherence and convenience for patients, while creating meaningful differentiation over competitors that are pursuing injectable assets. The single-tablet strategy demonstrates thoughtful consideration of real-world treatment dynamics in a chronic metabolic disease where long-term adherence is vital for successful outcomes.
The newly announced combination of ervogastat and Rezdiffra has evident potential. DGAT-2 inhibition can block triglyceride synthesis while THR-β agonism enhances lipid oxidation, creating complementary activity through distinct pathways. Ervogastat’s Phase IIb data, which showed 61% of patients achieving ≥50% liver fat reduction by MRI-PDFF, provides tangible evidence of potent anti-steatotic activity. While Pfizer’s trial failed to achieve statistical significance for ervogastat monotherapy, Madrigal is strategically choosing not to develop it as a monotherapy.
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By GlobalDataThe oral GLP-1 strategy showcases similar sophistication by Madrigal. Unlike Novo Nordisk’s Wegovy (semaglutide), Madrigal has opted not to pursue dramatic weight loss that would invite tolerability concerns, which it cited in its JPM presentation as a reason for Wegovy’s high discontinuation rates. Instead, Madrigal targets modest reduction based on compelling MAESTRO-NASH data showing patients achieving ≥5% weight loss demonstrated by meaningfully higher response rates of 39% versus 28% at the 80mg dose. By aiming for gradual, tolerable weight reduction, the company optimises vital fibrosis reduction while maintaining the tolerability profile that has driven Rezdiffra’s adoption.
Madrigal’s MASH F4c expansion strategy outlined at JPM 2026 demonstrates how indication expansion and combination development work synergistically. With approximately 245,000 cirrhotic patients facing 42-fold higher liver-related mortality risk, the addressable market is considerable. Success in the Phase III MAESTRO-NASH OUTCOMES trial in MASH F4 would substantially expand Rezdiffra’s market opportunity while creating ideal conditions for combination therapy adoption if monotherapy proves insufficient for the most severe patients.
Madrigal is executing a multifaceted strategy that balances near-term commercial success with long-term brand building. The company identified a massive unmet need, developed the first approved asset, executed a successful launch, and is now leveraging that success to consolidate its market position. Despite being a company that is less than two years into its first commercial launch, Madrigal appears set to become a mainstay in the MASH therapy space for the foreseeable future.
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