Eli Lilly has unveiled fibrosis results from a Phase 2 test of tirzepatide in patients with metabolic dysfunction-associated steatohepatitis, or MASH, which could help further increase the blockbuster drug’s market territory.
The placebo-controlled Phase 2 SYNERGY-NASH trial studied three doses of tirzepatide in 190 people with MASH, also referred to as NASH. In a key secondary endpoint measured across 155 participants, 51% to 54.9% of patients across the three treatment arms achieved a minimum one-stage improvement in fibrosis without worsening of their disease at 52 weeks, versus 21.3% to 25.2% of placebo cohorts (p<0.05), according to a late-breaking EASL International Liver Congress abstract.
While there was a lack of a clear dose relationship in this endpoint, delta between treatment arms and placebo “does look promising,” Jefferies analysts wrote in a Wednesday note. Tirzepatide was tested at 5 mg, 10 mg and 15 mg doses in the Phase 2.
Wednesday’s data led to share price drops for some of Lilly’s MASH competitors, namely Madrigal Pharmaceuticals, Akero Therapeutics and 89bio.
In February, Eli Lilly reported positive primary endpoint data on the proportion of patients who achieved MASH resolution without worsening of their disease. But the company was yet to detail the extent to which the treatment reduced liver fibrosis, only stating that the results for liver fibrosis reduction were “clinically meaningful.” Fibrosis is a key disease feature for MASH.
At the time, Lilly’s Chief Scientific Officer Dan Skovronsky said he was “really excited” about the data. The drugmaker is scheduled to hit the stage at EASL with its Phase 2 results on Saturday.
MASH competition heats up
Lilly’s MASH data mark a key milestone for the drug, which is currently marketed for type 2 diabetes and weight management. The drugmaker has plans to tap the broader cardiometabolic potential of the dual GIP/GLP-1 receptor agonist in MASH.
In March, the FDA approved the first treatment option for MASH under an accelerated pathway in the form of Madrigal’s oral THR-β agonist Rezdiffra. Madrigal CEO Bill Sibold previously told Endpoints News that GLP-1 approaches may perform best in early-stage MASH before there is fibrosis or significant fibrosis.
But Lilly’s positive secondary endpoint data Wednesday suggest a “double G” approach may be able to address more advanced forms of the disease, as the patients enrolled in the Phase 2 tirzepatide test had stage two or three fibrosis at baseline.
Tirzepatide’s results are competitive against Rezdiffra’s Phase 3 data, which saw 26% of patients given the drug’s highest 100 mg dose achieve a minimum one-stage improvement in liver fibrosis with no worsening of their disease at 24 weeks. But Akero’s FGF21 analog efruxifermin has shown the highest fibrosis improvement to date with 75% at 96 weeks in its Phase 2b trial.
Madrigal’s share price $MDGL was down 14% premarket Wednesday, while Areko’s $ARKO was down 7%. Elsewhere, 89bio — which is advancing its own FGF21 analog — saw its share price $ETNB drop 9%. In its Phase 2b trial, the 44 mg dose of pegozafermin saw 27% of patients achieve fibrosis improvement at 24 weeks.
Lilly’s registrational plans for tirzepatide in MASH are yet to be confirmed, the Jefferies analysts wrote.
Wednesday’s results bode well for dual GIP/GLP-1 agonists as a whole, including Roche’s CT-388, acquired during a $2.7 billion buyout of Carmot Therapeutics. Elsewhere, Amgen’s MariTide is taking a slightly different approach by mimicking GLP-1 but inhibiting GIP. Neither of these candidates is currently being investigated for MASH.
Editor’s note: This article was updated to add further context and share price movement.