Efruxifermin

GSK, Roche and Novo jumped into MASH with a multi-billion-dollar deal spree. Now the phase 3 data have to deliver. For years, MASH was where drug development dreams went to die. One trial after another failed. Companies bowed out. The field earned a reputation as one of biopharma’s most intractable challenges: a complex disease marked by numerous contributing factors that seemed too complicated to crack. Patients with a severe form of fatty liver disease called metabolic dysfunction-associated steatohepatitis—formerly known as nonalcoholic steatohepatitis (NASH)—were left with advice about diet and exercise, and doctors could offer little more than watchful waiting as inflammation and scarring progressed. Then, in March 2024, the narrative cracked. The FDA approved Madrigal Pharmaceuticals’ daily pill Rezdiffra for adults with noncirrhotic MASH and F2-F3 fibrosis. It was the first FDA-approved therapy for the disease, signaling that the bar could be met.Seventeen months later, in mid‑August 2025, Novo Nordisk’s Wegovy—already a blockbuster obesity drug—gained a label expansion to be used as a weekly treatment for adults with noncirrhotic MASH and moderate to advanced fibrosis. With a GLP-1 agonist in the mix, what had been a hepatology problem suddenly belonged to cardiometabolic medicine. Obesity drugs already have the prescribers and patient familiarity plus established ties with payers and PBMs that can speed coverage. That existing distribution network may aid in moving patients toward treatment for their liver disease. Despite the progress, a huge patient gap remains. In the U.S., there are roughly 22 million adults who have MASH, with about 9 million at clinically significant fibrosis (F2/F3)—the very segment Rezdiffra and Wegovy target—leaving many outside treatment today. Even within the label, a gap remains: In the phase 3 Maestro-NASH trial, once-daily Rezdiffra 80 mg and 100 mg achieved MASH resolution with no worsening of fibrosis in 25.9% and 29.9% of patients, respectively, compared to 9.7% with placebo at 52 weeks. Notably, roughly 14% of participants were already on GLP-1 agonists—underscoring the pull toward combination therapy.Against that backdrop, recent acquisitions exceeding $10 billion indicate that major pharma players continue to see a sizable opportunity in MASH. GSK, Roche and Novo stake their claims  GSK moved first among the latecomers. In May 2025, the company agreed to acquire efimosfermin from Boston Pharmaceuticals for $1.2 billion upfront and up to $800 million in milestones. The once‑monthly FGF21 analogue has since changed hands and is being positioned for phase 3 in steatotic liver diseases including MASH. The dosing cadence could give GSK an adherence and convenience case, provided efficacy holds up in late-stage trials. Roche followed in September. The company—long synonymous with cancer care—agreed to acquire 89bio for up to $3.5 billion, capturing pegozafermin, an engineered FGF21 analogue now in phase 3 trials. CEO Thomas Schinecker, Ph.D., framed the deal as portfolio expansion and a bridge to combination approaches across cardiovascular, renal and metabolic diseases. Novo Nordisk, the GLP-1 trailblazer, then announced plans to acquire Akero Therapeutics for about $4.7 billion upfront ($54 per share) plus a $6‑per‑share contingent value right tied to full U.S. approval of efruxifermin in compensated cirrhosis by June 30, 2031—bringing a plausible fibrosis partner to graft on to Wegovy’s newly minted MASH label, if late‑stage data cooperate.  Behind the deal math sits a new clinical reality. Rezdiffra opened the regulatory door and has outpaced early sales projections—more than 17,000 patients were on the therapy by March 31, 2025—and Wegovy’s new label pulled liver disease into one of the most powerful distribution networks in modern medicine. A Spherix Global Insights survey conducted in August—shortly after Wegovy’s MASH label expansion—found that nearly two-thirds of gastroenterologists and hepatologists planned to prescribe the Novo drug within three months, with many anticipating combining it with other therapies for patients with advanced fibrosis. The stack emerges   If the first wave of MASH therapies showed what was possible, the second wave shows what companies believe is necessary. FGF21 analogues—including pegozafermin (Roche/89bio), efruxifermin (Novo/Akero) and efimosfermin (GSK)—aim to reach fibrosis and inflammation in ways incretins may not, especially in patients further along the disease arc. Midstage trials have shown reductions in liver fat and encouraging signals on fibrosis biomarkers. Akero’s 96-week analysis, presented earlier this year, drew “transformational” praise from some analysts, even after an earlier 36-week readout fell short. But phase 3 trials are the industry's truth serum. Those readouts, expected to begin next year, will test whether the science can support the surge of investment that's flowed into the field.The strategy driving that investment is clear: combination therapy. Roche has assembled a modular metabolic stack: CT‑388, a GLP‑1/GIP dual agonist acquired with Carmot Therapeutics; an amylin analogue partnership with Zealand Pharma (petrelintide), including plans for fixed‑dose combinations with CT‑388; and now an FGF21 anchor via 89bio. The company is building from the outside in, collecting mechanisms to test in combination with one another. Madrigal, the field’s first commercial mover, is preparing for the same future. In July 2025, it licensed global rights to CSPC Pharmaceutical’s preclinical oral GLP‑1, SYH2086, for $120 million upfront and up to $2 billion in milestones—explicitly to pair with Rezdiffra. About 25% of Rezdiffra patients are already on a GLP‑1, Madrigal CEO Bill Sibold pointed out in the company's first-quarter earnings presentation.  Novo Nordisk aims to leverage Wegovy's track record in obesity as it extends its efforts to MASH. The Danish pharma boasts a GLP‑1 backbone with a fresh MASH label, onto which it aims to graft Akero’s FGF21 program if the data hold. GSK adds a once-monthly FGF21 to that mix. If efimosfermin delivers fibrosis and other clinical benefits with fewer injections, the company gains both a differentiated marketing angle and leverage at the combination table. Provisional momentum The crowded landscape belies how provisional it remains. Rezdiffra's early success is notable, but Madrigal is naturally pushing to expand beyond F2-F3 noncirrhotic patients. Wegovy's label gives Novo a foothold among noncirrhotic patients with significant fibrosis, but confirmatory outcome data still hang on the horizon. The FGF21 class must show that biomarker gains translate into fibrosis improvements and real clinical benefit, substantial hurdles proportionate to a disease area that humbled an entire generation of researchers.Yet capital keeps flooding in. Roche's $3.5 billion pact for 89bio and Novo's move on Akero signal serious sales expectations. These large pharma companies with manufacturing scale, market access proficiency and deep pockets are stepping in deliberately. GSK is positioned to challenge both with a monthly FGF21 dosing that could matter to prescribers and payers.The stakes are considerable. The MASH sweepstakes went from unsolvable to inevitable in 18 months, with billions committed betting that GLP-1s and FGF21s can work in combination. Early signals—patient data, prescriber intent, midstage biomarkers—suggest the strategy could work. But if phase 3 trials fail on fibrosis, outcomes or safety, regulators may balk. Add liver diagnostics and specialist referrals, and access gets even tougher.