Latest news with #efruxifermin
Medscape
09-05-2025
- Health
- Medscape
Efruxifermin Shows Fibrosis Reduction in MASH Cirrhosis
AMSTERDAM — A once daily, 50 mg dose of efruxifermin reduced fibrosis at 96 weeks in patients with compensated cirrhosis due to metabolic dysfunction-associated steatohepatitis (MASH) compared with placebo, but it did not significantly reduce fibrosis at 36 weeks (primary endpoint), according to results from the phase 2b SYMMETRY trial. Efruxifermin is a long-acting, bivalent fibroblast growth factor 21 analogue. At 96 weeks of treatment, a statistically significant 29% of patients had at least one stage of fibrosis improvement without MASH worsening (secondary outcome) compared with 11% on placebo. Results also suggested improvements in MASH-related histologic findings, non-invasive markers of liver injury and fibrosis, as well as markers of glucose and lipid metabolism at 96 weeks. Now the 50 mg dose of efruxifermin is being investigated in phase 3 development. Mazen Noureddin, MD, MHSc Academic-clinician Mazen Noureddin, MD, MHSc, of the Sherrie and Alan Conover Center for Liver Disease and Transplantation at Houston Methodist Hospital, Texas, presented the findings here at the at the European Association for the Study of the Liver (EASL) Congress 2025. The work was published simultaneously in The New England Journal of Medicine . Noureddin said that, for the first time, they showed 'significant, unprecedented improvement in fibrosis' on the regimen. He added that the 'histologic improvement in fibrosis corroborated with non-invasive tests, presenting an overall picture of liver injury and function that suggests liver health is maintained or slightly improved by efruxifermin compared to placebo.' Despite being a major cause of liver failure and transplantation, there are currently no approved therapies that reverse fibrosis in MASH-related cirrhosis. Efruxifermin has shown antifibrotic effects in earlier studies of patients with less advanced disease (F2-F3 fibrosis). Now, this phase 2b, randomized, placebo-controlled, double-blind trial, shows efficacy and safety with efruxifermin in patients with MASH who had biopsy-confirmed compensated cirrhosis at stage 4 fibrosis. The Trial SYMMETRY was conducted across 45 sites in the US, Mexico, and Puerto Rico. It enrolled 181 adults with biopsy-confirmed compensated cirrhosis due to MASH (Child-Pugh A), 80% of whom had diabetes and obesity. Patients were at high risk for hepatic decompensation. Participants were 18-75 years of age, had liver histologic features consistent with MASH, and had compensated cirrhosis (stage 4 fibrosis with a Child-Pugh score of 5 or 6). They also had type 2 diabetes or two components of metabolic syndrome comprising obesity, dyslipidemia, elevated blood pressure, and elevated fasting glucose level. Approximately 80% of the patients had biopsy-confirmed MASH. Patients received weekly subcutaneous efruxifermin (28 mg or 50 mg) or placebo in a 1:1:1 ratio. Liver biopsies were obtained at weeks 36 and 96 and were included in the intention-to-treat and safety analyses. Overall, liver biopsy data were available for 154 patients at week 36 and for 134 patients at week 96. The primary endpoint comprised a reduction of at least one stage of fibrosis without worsening of MASH at week 36, while the same measure comprised the secondary outcome at week 96. At 36 weeks, in the intent-to-treat analysis, a reduction in fibrosis without worsening of MASH was seen in 8/61 patients (13%) in the placebo group, 10/57 patients (18%) in the 28 mg efruxifermin group (95% CI, -11 to 17; P = .62), and 12/63 patients (19%) in the 50 mg efruxifermin group (95% CI, -10 to 18; P = .52). Referring to the 36-week completer analysis, Noureddin reported, '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],' he reported. In the intent-to-treat analysis, at week 96, a reduction in fibrosis without worsening of MASH occurred in 7/61 patients (11%) in the placebo group, in 12/57 patients (21%) in the 28 mg efruxifermin group (95% CI, -4 to 24), and in 18/63 patients (29%) in the 50 mg efruxifermin group (95% CI, 2-30). 'It was up to 29% in the 50 mg compared with 11%, and that's an 18% statistically significant difference [ P < .05].' The proportion of week 36 responders who sustained response to week 96 were 50% (n = 4), 67% (n = 6), and 75% (n = 9), in the placebo, 28 mg, and 50 mg groups, respectively. Expanded response (non-response at week 36 but response at week 96) was 8% (n = 3), 19% (n = 6), and 26% (n = 9) respectively. 'This emphasizes the role of ongoing treatment in cirrhotic patients,' said Noureddin. He also added that they saw 'consistent responses across multiple baseline subgroups for the primary histological endpoint and at week 96 with the 50 mg.' Nearly all participants (99% on efruxifermin and 97% on placebo) reported adverse events. Any serious adverse events were reported in 26%, 24%, and 18% in the 28 mg, 50 mg, and placebo groups, respectively. Gastrointestinal side effects were most common: diarrhea (42%, 54%, and 30% on 28 mg, 50 mg, and placebo, respectively), nausea (30%, 46%, 30%, respectively), and increased appetite (16%, 40%, 7%, respectively) and mostly of mild-to-moderate nature. Administration-site reactions (erythema) were also more common with efruxifermin (13%, 16%, and 6%, respectively). After week 36 and prior to week 96, discontinuations due to adverse events were 0%, 2%, and 3% in the placebo, 28 mg, and 50 mg, respectively. 'After week 36, there were very few discontinuations due to side effects,' reported Noureddin. Poor bone health is a common complication of cirrhosis, and across all treatment groups, 43% of participants had osteopenia at baseline, but only 4% were treated with bisphosphonates. Placebo-adjusted, significant relative reductions in bone mineral density (-5%) for spine and hip were observed for both treatment groups at week 96 or about 2%-3% per year. The number of participants experiencing fractures was equal across all treatment groups, added Noureddin. Commenting on the study, delegate and chairman of the Global NASH Council, Zobair M Younossi, MD, professor and chairman of the department of medicine at Inova Fairfax Medical Campus, Fairfax County, Virgina, told Medscape Medical News , 'The key to this whole area is that there are treatments that have been developed for non-cirrhotic MASH, F2 and F3, but there is currently nothing that is positive for people with cirrhosis and MASH. This study shows there is improvement in all categories even in those with diabetes and even when they are controlled for some alcohol consumption.' He added, '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 study was supported by Akero Therapeutics. Noureddin declared grants, consultant roles, and stock options from many pharmaceutical companies, including Akero. Younossi reported no relevant financial relationships.
Yahoo
09-05-2025
- Business
- Yahoo
Akero Therapeutics Presents Week 96 Results from Phase 2b SYMMETRY Clinical Trial of Efruxifermin in Patients with Compensated Cirrhosis Caused by MASH Showing Fibrosis Improvement without Worsening of MASH at the EASL Congress 2025
SOUTH SAN FRANCISCO, Calif., May 09, 2025 (GLOBE NEWSWIRE) -- Akero Therapeutics, Inc. (Nasdaq: AKRO), a clinical-stage company developing transformational treatments for patients with serious metabolic diseases marked by high unmet medical need, presented results from the Phase 2b SYMMETRY trial demonstrating the potential of efruxifermin (EFX) to improve fibrosis in compensated cirrhosis (F4) caused by metabolic dysfunction-associated steatohepatitis (MASH), in a late-breaking oral presentation at the European Association for the Study of the Liver (EASL) Congress 2025 taking place May 7-10, in Amsterdam, the Netherlands. 'Compensated cirrhosis due to MASH remains a high unmet medical need, leaving patients with a poor prognosis and currently no effective treatment options beyond liver transplant,' said Kitty Yale, chief development officer of Akero. 'These data presented at the EASL Congress 2025 differentiate EFX from other approved or investigational MASH treatments as the first to demonstrate fibrosis reversal in patients with MASH caused by cirrhosis. We look forward to continuing evaluation of EFX across all stages of MASH in our Phase 3 SYNCHRONY program.' 'Patients with cirrhosis caused by MASH could face a 50 percent chance of dying within five years without a liver transplant,' said Mazen Noureddin, M.D., Professor of Medicine and Transplant Hepatologist at Houston Methodist Hospital, and principal investigator for the SYMMETRY study. 'EFX's powerful anti-fibrotic activity, as observed in the Phase 2b SYMMETRY trial and currently being evaluated in Phase 3, has the potential to be the most substantial medical breakthrough in my career as a treating physician.' Week 96 data presented from SYMMETRY, a Phase 2b trial evaluating the efficacy and safety of Akero's lead product candidate, EFX, in patients with biopsy-confirmed compensated cirrhosis (F4) due to MASH, showed fibrosis reduction without MASH worsening by both completer and intent-to-treat (ITT) analyses after 96 weeks. In the pre-specified analysis of patients with baseline and week 96 biopsies (N=134), 39% of patients treated with EFX 50mg had fibrosis improvement compared to 15% of placebo-treated patients (p=0.009). In the ITT population (N=181), with missing week 96 biopsies treated as non-responders, 29% of patients in the EFX 50mg group experienced this improvement, compared to 11% for placebo (p=0.031). The primary endpoint of the SYMMETRY study was ≥1 stage fibrosis improvement with no worsening of MASH at Week 36. A numerical improvement was observed in the EFX groups vs. placebo at Week 36 but the differences were not statistically significant. Summary of Week 96 Fibrosis Improvement without MASH Worsening Secondary Endpoint Primary Analysis (N=134)1 ITT Analysis (N=181)2 Histology Endpoint3 (Proportion of Patients) Placebo(N=47) EFX 28mg(N=41) EFX 50mg(N=46) Placebo(N=61) EFX 28mg(N=57) EFX 50mg(N=63) ≥1 stage fibrosis improvement without worsening MASH (%) 15 29 39 ** 11 21 29 * 1 All patients with baseline and week 96 biopsies2 The 47 randomized and dosed patients who had missing biopsies at week 96 are treated as non-responders in the ITT analysis (without imputation).3 Biopsies scored independently by two pathologists; third available to adjudicate (which was not required)* p<0.05, ** p<0.01, versus placebo (Cochran-Mantel-Haenszel test). Comparison of the proportion of patients with a fibrosis reduction at Week 36 and Week 96 in the pre-specified analysis of patients with baseline and week 96 biopsies, showed more than a doubling of placebo-adjusted treatment effect for the EFX 50mg group, from 10% to 24%. This increase in effect size shows the importance of longer treatment with EFX for patients with compensated cirrhosis (F4) as compared to responses observed in trials of EFX in patients with earlier stage fibrosis (F2 or F3). The larger treatment effect observed after 96 weeks is corroborated by changes in noninvasive measures of liver fibrosis and injury. For example, two key non-invasive measures of the extent of fibrosis development in the whole liver, ELF test score and liver stiffness by Fibroscan, showed continuing improvement over 96 weeks for the 50mg EFX group. Newly presented analyses showed EFX's potential to improve fibrosis among patients with compensated cirrhosis across key subgroups. Patients responded to EFX 50mg after 96 weeks regardless of type 2 diabetes status or treatment with GLP-1 medications or statins at baseline. The safety and tolerability profile of EFX was consistent with previous trials. The most frequent adverse events with EFX were gastrointestinal (diarrhea, nausea, increased appetite) and most were mild to moderate and transient. All serious adverse events were deemed to be unrelated to study drug. Details for the presentation are as follows: Title: Efruxifermin improves fibrosis in participants with compensated cirrhosis due to MASH: results of a 96-week, randomized, double-blind, placebo-controlled, phase 2b trial (SYMMETRY)Speaker: Mazen Noureddin, M.D., Professor of Medicine, Houston Methodist Hospital and Director, Houston Research InstituteDate/Time: Friday, May 9, 2025, from 12:15 pm – 12:30 pm CET Abstract Identifier: GS-012Oral Session: General Session 2 About Cirrhosis Due to MASH Cirrhosis due to MASH (metabolic dysfunction-associated steatohepatitis) is a life-threatening disease with high risk of liver failure, cancer, and death. By 2030, an estimated 3 million Americans are projected to have MASH cirrhosis, which is the fastest growing cause of liver transplants and liver cancer in the United States and Europe. About the SYMMETRY Study SYMMETRY was a Phase 2b, multicenter, randomized, double-blind, placebo-controlled, dose-ranging trial in adult patients with biopsy-confirmed compensated cirrhosis (F4, Child-Pugh A) due to MASH. The study randomized 182 patients, and 181 received once-weekly subcutaneous EFX 28mg or 50mg, or placebo for 96 weeks. The primary efficacy endpoint was the proportion of patients with ≥1 stage fibrosis improvement without worsening of MASH at Week 36. Secondary efficacy measures at Week 96 included ≥1 stage fibrosis improvement without worsening of MASH, MASH resolution, change from baseline in liver enzymes, noninvasive markers of liver fibrosis, serum markers of glucose and lipid metabolism, as well as safety and tolerability measures. About EFXEfruxifermin (EFX), Akero's lead product candidate for MASH, is currently being evaluated in three ongoing Phase 3 studies. In multiple Phase 2 studies, EFX has been observed to reverse fibrosis (including compensated cirrhosis), resolve MASH, reduce non-invasive markers of fibrosis and liver injury, and improve insulin sensitivity and lipoprotein profile. This holistic profile offers the potential to address the complex, multi-system disease state of all stages of MASH, including improvements in risk factors linked to cardiovascular disease – the leading cause of death among MASH patients. Engineered to mimic the biological activity profile of native FGF21, EFX is designed to offer convenient once-weekly dosing and has been generally well-tolerated in clinical trials to date. About Akero Therapeutics Akero Therapeutics is a clinical-stage company developing transformational treatments for patients with serious metabolic diseases marked by high unmet medical need, including metabolic dysfunction-associated steatohepatitis (MASH). Akero's lead product candidate, efruxifermin (EFX), is currently being evaluated in three ongoing Phase 3 clinical studies: SYNCHRONY Histology in patients with pre-cirrhotic (F2-F3 fibrosis) MASH, SYNCHRONY Outcomes in patients with compensated cirrhosis (F4) due to MASH, and SYNCHRONY Real-World in patients with MASH or MASLD (metabolic dysfunction-associated steatotic liver disease). The Phase 3 SYNCHRONY program builds on the results of two Phase 2b clinical trials, the HARMONY study in patients with pre-cirrhotic MASH and the SYMMETRY study in patients with compensated cirrhosis due to MASH. Akero is headquartered in South San Francisco. Visit us at and follow us on LinkedIn and X for more information. Forward Looking Statements Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements'' within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements, including, but not limited to, statements regarding Akero's business plans and objectives; the potential therapeutic effects and anti-fibrotic activity of EFX, as well as the dosing, safety and tolerability of EFX, the future potential and long-term benefits of EFX following the preliminary topline week 96 results of Akero's Phase 2b SYMMETRY study and the ongoing SYNCHRONY Phase 3 program. Any forward-looking statements in this press release are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. Risks that contribute to the uncertain nature of the forward-looking statements include: the success, cost, and timing of Akero's product candidate development activities and planned clinical trials; Akero's ability to execute on its strategy; positive results from any of its clinical studies may not necessarily be predictive of the results of future or ongoing clinical studies; regulatory developments in the United States and foreign countries; Akero's ability to fund operations; as well as those risks and uncertainties set forth more fully under the caption "Risk Factors'' in Akero's most recent Annual Report on Form 10-K and Quarterly Report on Form 10-Q, as filed with the Securities and Exchange Commission (SEC) as well as discussions of potential risks, uncertainties and other important factors in Akero's other filings and reports with the SEC. All forward-looking statements contained in this press release speak only as of the date on which they were made. Akero undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made. Investor Contact:Christina TartagliaPrecision AQ212.362.1200IR@ Media Contact:Peg RusconiDeerfield in to access your portfolio
