Approval market ignites late-stage clinical competition

Madrigal Pharmaceuticals (MDGL)'s resmetirom, a liver-selective thyroid hormone receptor beta (THR-beta) agonist, became the first treatment to receive FDA accelerated approval for non-cirrhotic F2–F3 MASH on March 14, 2024. The confirmatory clinical trial, MAESTRO-NASH, will continue to evaluate clinical benefit until 2029. Novo Nordisk (NVO)'s semaglutide, a GLP-1 receptor agonist, received accelerated approval for the same patient group on August 15, 2025, expanding the standard-of-care competition to include direct-acting liver therapies and weight/metabolic improvement agents. The global MASH treatment market is projected to grow from USD 8.13B in 2025 to USD 33.02B in 2035.

Altimmune and Inventiva aim for phase 3 readouts

Altimmune (ALT)'s pemvidutide, a dual-agonist of glucagon and GLP-1 receptors, received FDA Breakthrough Therapy designation and initiated a phase 3 trial in F2–F3 patients in August 2026. It directly competes with semaglutide by targeting weight loss, hepatic fat, inflammation, and fibrosis, while differentiating through glucagon-based liver action. Inventiva (IVA)'s lanifibranor, an oral pan-PPAR agonist that simultaneously activates PPAR alpha, delta, and gamma, is expected to report NATiV3 phase 3 results in the second half of 2026. Its reliance on a single core asset and a 50% workforce reduction in 2025 create a high leverage scenario where success could be transformative, but failure would be concentrated.

Gene-targeted and cirrhosis therapies exploit gaps

Arrowhead Pharmaceuticals (ARWR) is building an RNAi strategy tailored to patient genotypes, with phase 2b trials for HSD17B13-targeting GSK4532990, phase 1 trials for PNPLA3-targeting ARO-PNPLA3, and early development for INHBE·Activin E-targeting ARO-INHBE. ARO-PNPLA3 was licensed to Madrigal in May 2026, expanding resmetirom's potential for combination therapy. Galactin Therapeutics (GALT)'s belapectin, a galectin-3 inhibitor targeting MASH cirrhosis and portal hypertension, has reached agreement with the FDA on phase 3 primary endpoints and the pathway for full approval. Since current approvals are limited to non-cirrhotic F2–F3 patients, F4 cirrhosis remains the largest unmet clinical and commercial need.

Combination therapies and big pharma acquisitions reshape market structure

Sagimet Biosciences (SGMT)'s denifanstat, an oral FASN inhibitor that blocks new hepatic fat synthesis, has received FDA Breakthrough Therapy designation. It demonstrated tolerability in combination with resmetirom in phase 1 and plans to initiate phase 2 efficacy trials in the second half of 2026, contingent on securing non-dilutive funding. In 2025, GSK acquired a monthly FGF21 analog, epimorespim alpha, for up to USD 2.0B, while Roche and Novo Nordisk acquired 89bio and Akero for up to USD 3.5B and USD 5.2B, respectively. These three deals highlight the FGF21 family's recognition as a key late-stage MASH anti-fibrotic asset and a potential GLP-1 combination partner.