Efruxifermin is an intravenous and subcutaneous long-acting, bivalent analogue of fibroblast growth factor 21. It holds great potential in treating patients with MASH and patients with biopsy-proven compensated cirrhosis. As such, Efruxifermin is making its phase 3 through development. Researchers in North Carolina have been giving a 50 mg dose of the treatment, enough to reduce fibrosis in the majority of patients with advanced liver disease.
These new pearls of wisdom stem from the REVEAL trial. This phase 2b study was a randomized, placebo-controlled double-blind trial at 45 sites in the United States, Mexico and Puerto Rico. In the trial, Efruxifermin was given once weekly by subcutaneous injection in either 28 mg or 50 mg doses. The single patients trial recruited MASH patients that had progressed to at least stage 4 fibrosis. This stage represents an important turning point in the natural history of liver disease.
By week 36 of the trial, data indicated that the results were very promising. Each patient who received Efruxifermin at the 50 mg dosage saw an extraordinary average 19% lowering of fibrosis and did so without any worsening of MASH. This trend persisted at 96 weeks, with those on a consistent dosage showing an overall 29% decrease in fibrosis. The drug significantly reversed fibrosis by 39% by at least one stage. By contrast, the placebo group improved by only 15%.
Efruxifermin’s antifibrotic effects have been observed in previous studies of patients with milder disease (F2-F3 fibrosis). Together, these discoveries point toward its promise as a new, fine-tuned treatment option with the ability to adapt across multiple stages of liver disease.
“We see here, 24% in the 50 mg group compared with 14% in those on placebo [and 22% on the 28-mg dose]. When they continue treatment up to 96 weeks, we saw up to 39% improvement [50-mg dose] in fibrosis by one stage without worsening of MASH compared to 15% placebo [and 29% with 28 mg]. This is a difference of 24% [between placebo and 50 mg] that was statistically significant (P < .01),” – Mazen Noureddin.
Efruxifermin was associated with gastrointestinal side effects, which were some of the most frequently reported side effects among trial participants receiving Efruxifermin. These included diarrhea, nausea, and increased appetite. Skin reactions at the administration site, such as erythema, were largely reported in the Efruxifermin group. Specifically, the rates were 13% for the 28 mg dose, 16% for the 50 mg dose and just 6% for the placebo.
Nearly 100 percent of all participants experienced some adverse event. These events occurred in 99% of participants on Efruxifermin and 97% of participants in placebo, the figures demonstrated. Such extreme rates truly exemplify the necessity for heightened awareness regarding patient safety throughout the treatment continuum.
“It was up to 29% in the 50 mg compared with 11%, and that’s an 18% statistically significant difference (P < .05),” – Mazen Noureddin.
Second, the study’s results highlight the importance of long-term management among cirrhotic patients. “This emphasizes the role of ongoing treatment in cirrhotic patients,” noted Noureddin. Efruxifermin’s possible impact is much more than statistical significance. We applaud the report for its efforts to raise awareness about this urgent need in liver disease care management.
To understand the importance of these findings, Dr. Zobair M Younossi, Professor of Medicine and Health Policy, George Washington University. He continued, “Although there are treatments readily available for non-cirrhotic MASH at F2 and F3 stages, there are no more effective options available for those who are afflicted with cirrhosis and MASH. These results highlight the remarkable progress made in all three areas. That’s true even for people with diabetes, after taking into account light to moderate alcohol use.
He further emphasized the therapeutic implications of Efruxifermin: “I think that the best aspect of this is that it gives us a potential treatment for those patients who are at highest risk for bad outcomes in MASLD, which are those with cirrhosis.”
The original research was funded by Akero Therapeutics, although multiple other financial ties between the developer and other pharma companies have been reported. Efruxifermin is currently in phase 3 clinical trials. Its advance results open the door to innovative treatment strategies for controlling MASH and other liver diseases.
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