Akero Therapeutics Reports Preliminary Topline Results Showing Statistically Significant Reversal of Compensated Cirrhosis (F4) Due to MASH—by Both Completer and ITT Analyses—at Week 96 in Phase 2b SYMMETRY Study
Akero Therapeutics (NASDAQ: AKRO) has announced significant topline results from its Phase 2b SYMMETRY study evaluating efruxifermin (EFX) in patients with compensated cirrhosis due to MASH. The study demonstrated statistically significant reversal of cirrhosis at Week 96:
- Among patients with baseline and week 96 biopsies, 39% of the 50mg EFX group showed ≥1 stage improvement in fibrosis with no worsening of MASH, compared to 15% for placebo (24% effect size).
- In the Intent to Treat analysis, 29% of the 50mg EFX group demonstrated improvement, compared to 12% for placebo (17% effect size).
The study revealed stronger results in patients not taking GLP-1 at baseline, with 45% showing cirrhosis reversal in the 50mg group versus 17% for placebo. EFX was generally well-tolerated, with most adverse events being grade 1 or 2 gastrointestinal issues.
Akero Therapeutics (NASDAQ: AKRO) ha annunciato risultati preliminari significativi dal suo studio di Fase 2b SYMMETRY che valuta efruxifermin (EFX) in pazienti con cirrosi compensata dovuta a MASH. Lo studio ha dimostrato una significativa inversione della cirrosi alla Settimana 96:
- Tra i pazienti con biopsie alla baseline e alla settimana 96, il 39% del gruppo EFX a 50mg ha mostrato un miglioramento di almeno 1 stadio nella fibrosi senza deterioramento della MASH, rispetto al 15% per il placebo (dimensione dell'effetto del 24%).
- Nell'analisi Intent to Treat, il 29% del gruppo EFX a 50mg ha dimostrato miglioramenti, rispetto al 12% per il placebo (dimensione dell'effetto del 17%).
Lo studio ha rivelato risultati più forti nei pazienti che non assumevano GLP-1 alla baseline, con il 45% che mostrava inversione della cirrosi nel gruppo a 50mg rispetto al 17% per il placebo. L'EFX è stato generalmente ben tollerato, con la maggior parte degli eventi avversi che si sono manifestati come problemi gastrointestinali di grado 1 o 2.
Akero Therapeutics (NASDAQ: AKRO) ha anunciado resultados preliminares significativos de su estudio de Fase 2b SYMMETRY, que evalúa el efruxifermin (EFX) en pacientes con cirrosis compensada debida a MASH. El estudio demostró una reversión estadísticamente significativa de la cirrosis a la Semana 96:
- Entre los pacientes con biopsias en la línea base y en la semana 96, el 39% del grupo EFX de 50mg mostró una mejora de al menos 1 estadio en la fibrosis sin empeoramiento de MASH, en comparación con el 15% para el placebo (tamaño del efecto del 24%).
- En el análisis por intención de tratar, el 29% del grupo EFX de 50mg demostró mejora, en comparación con el 12% para el placebo (tamaño del efecto del 17%).
El estudio reveló resultados más sólidos en pacientes que no tomaban GLP-1 en la línea base, con un 45% mostrando reversión de la cirrosis en el grupo de 50mg frente al 17% para el placebo. El EFX fue generalmente bien tolerado, con la mayoría de los efectos adversos siendo problemas gastrointestinales de grado 1 o 2.
Akero Therapeutics (NASDAQ: AKRO)는 MASH로 인한 보상성 간경변증 환자를 대상으로 efruxifermin (EFX)의 2b 상기 SYMMETRY 연구에서 중요한 상위 결과를 발표했습니다. 이 연구는 96주에서 간경변증의 통계적으로 유의미한 역전을 보여주었습니다:
- 기저선 및 96주 생검이 있는 환자 중에서 50mg EFX 그룹의 39%가 MASH의 악화 없이 섬유화의 ≥1단계 개선을 보였으며, 이는 위약의 15%보다 높습니다 (효과 크기 24%).
- 치료 의도 분석에서는 50mg EFX 그룹의 29%가 개선을 보여주어, 위약의 12%에 비해 (효과 크기 17%) 개선되었습니다.
이 연구는 기저선에서 GLP-1을 복용하지 않은 환자에서 더 강한 결과를 보였으며, 50mg 그룹에서 간경변증이 역전된 비율은 45%, 위약군은 17%였습니다. EFX는 일반적으로 잘 견디며, 대부분의 이상반응은 1도 또는 2도의 위장 문제로 나타났습니다.
Akero Therapeutics (NASDAQ: AKRO) a annoncé des résultats préliminaires significatifs de son étude de Phase 2b SYMMETRY évaluant l'efruxifermin (EFX) chez des patients atteints de cirrhose compensée due à MASH. L'étude a montré une inversion statistiquement significative de la cirrhose à la Semaine 96 :
- Parmi les patients ayant subi des biopsies à la base et à la semaine 96, 39% du groupe EFX à 50mg ont montré une amélioration d'au moins 1 stade dans la fibrose sans aggravation de MASH, par rapport à 15% pour le placebo (taille de l'effet de 24%).
- Dans l'analyse des intentions de traitement, 29% du groupe EFX à 50mg ont démontré une amélioration, par rapport à 12% pour le placebo (taille de l'effet de 17%).
L'étude a révélé des résultats plus solides chez les patients ne prenant pas de GLP-1 à la base, avec 45% montrant une inversion de la cirrhose dans le groupe à 50mg contre 17% pour le placebo. L'EFX a généralement été bien toléré, la plupart des effets indésirables étant des problèmes gastro-intestinaux de grade 1 ou 2.
Akero Therapeutics (NASDAQ: AKRO) hat bedeutende vorläufige Ergebnisse aus seiner Phase-2b-Studie SYMMETRY veröffentlicht, die efruxifermin (EFX) bei Patienten mit kompensierter Zirrhose aufgrund von MASH bewertet. Die Studie zeigte eine statistisch signifikante Umkehrung der Zirrhose in Woche 96:
- Unter den Patienten mit Biopsien zu Beginn und in Woche 96 zeigten 39% der EFX-Gruppe mit 50mg eine Verbesserung um mindestens 1 Stadium in der Fibrose, ohne eine Verschlechterung von MASH im Vergleich zu 15% für das Placebo (Effektgröße von 24%).
- In der Analyse der Behandlungsabsicht demonstrierten 29% der EFX-Gruppe mit 50mg eine Verbesserung im Vergleich zu 12% für das Placebo (Effektgröße von 17%).
Die Studie ergab stärkere Ergebnisse bei Patienten, die zu Beginn kein GLP-1 einnahmen, wobei 45% in der EFX-Gruppe eine Umkehrung der Zirrhose zeigten im Vergleich zu 17% für das Placebo. EFX wurde im Allgemeinen gut vertragen, wobei die meisten unerwünschten Ereignisse Grad 1 oder 2 gastrointestinale Probleme waren.
- Statistically significant reversal of cirrhosis in 39% of 50mg EFX group (p=0.009)
- More than doubling of effect size from weeks 36 to 96 in 50mg group (10% to 24%)
- 45% cirrhosis reversal rate in non-GLP-1 patients with 50mg EFX
- Favorable safety profile with no drug-related serious adverse events
- Presence of gastrointestinal adverse events (diarrhea, nausea)
- Lower efficacy in ITT analysis (29%) compared to completer analysis (39%)
Insights
The SYMMETRY trial results represent a potential watershed moment in MASH treatment. The 39% cirrhosis reversal rate in the 50mg EFX group (p=0.009) is unprecedented in the field of liver disease therapeutics. Even the more conservative ITT analysis showed a 29% response rate (p=0.031), maintaining statistical significance.
Several aspects make these results particularly compelling:
- The doubling of effect size from weeks 36 to 96 (10% to 24%) suggests increasing benefits with longer treatment duration - critical for a chronic condition like MASH
- The subgroup analysis excluding GLP-1 users showed an even more robust 45% response rate, differentiating EFX's mechanism from popular weight-loss drugs
- The biomarker data strongly supports the histological findings - particularly the 0.53-point reduction in ELF score and 24% reduction in liver stiffness for the 50mg group
The safety profile appears manageable, with primarily Grade 1-2 gastrointestinal events and no treatment-related serious adverse events. This favorable benefit-risk profile is important for a drug targeting chronic use in a large patient population.
These results are particularly significant given that compensated cirrhosis represents the most severe form of MASH before decompensation, where mortality risk increases dramatically. The ability to reverse cirrhosis could fundamentally alter the disease trajectory for these high-risk patients.
The SYMMETRY results position EFX as a potential first-in-class therapy for MASH cirrhosis, addressing a critical unmet need in a market with no approved treatments. The robust efficacy data, particularly in cirrhosis reversal, could support premium pricing and favorable reimbursement decisions.
Key market implications:
- First-mover advantage in the high-value cirrhotic MASH segment, where patients face significant mortality risk
- Differentiated positioning from GLP-1s, supported by superior efficacy in non-GLP-1 users (45% response rate)
- Strong safety profile supporting chronic use, critical for market adoption and payer acceptance
- Multiple supportive biomarkers that could facilitate real-world monitoring of treatment response
The data's strength could support broad label claims and favorable positioning in treatment guidelines. The demonstrated benefits in cirrhosis reversal could justify premium pricing, particularly given the high costs associated with liver transplantation and complications of advanced liver disease.
Among patients with baseline and week 96 biopsies,
By ITT analysis, with all missing week 96 biopsies treated as failures,
Investor webcast at 8:00 am ET Monday, January 27, 2025
SOUTH SAN FRANCISCO, Calif., Jan. 27, 2025 (GLOBE NEWSWIRE) -- Akero Therapeutics, Inc. (Nasdaq: AKRO), a clinical-stage company developing transformational treatments for patients with serious metabolic disease marked by high unmet medical need, today released preliminary topline week 96 results from SYMMETRY, a Phase 2b study evaluating the efficacy and safety of its lead product candidate efruxifermin (EFX) in patients with biopsy-confirmed compensated cirrhosis (F4), Child-Pugh Class A, due to metabolic dysfunction-associated steatohepatitis (MASH). Among patients with baseline and week 96 biopsies (n=134),
With more than a doubling of effect size from weeks 36 to 96 in the 50mg group (from
In a subgroup of patients with baseline and week 96 biopsies who were not taking GLP-1 at baseline (n=97),
“Until today, we’ve not had the prospect of an effective treatment for compensated cirrhosis due to MASH, which is associated with high rates of short-term morbidity and mortality,” said Mazen Nourredin, M.D., Professor of Medicine and Transplant Hepatologist at Houston Methodist Hospital, and principal investigator for the SYMMETRY study. “Now we have reason to be optimistic about the future potential of EFX as a much-needed treatment for cirrhosis, if approved. I’m so happy for my patients and patients all around the world.”
Summary of Week 96 Reversal of Cirrhosis Endpoint
| Primary Analysis (N=134)1 | ITT Analysis (N=181)2 | |||||
| Histology Endpoint3 (Proportion of Patients) | Placebo (N=47) | 28mg (N=41) | 50mg (N=46) | Placebo (N=61) | 28mg (N=57) | 50mg (N=63) |
| ≥1 stage fibrosis improvement without worsening MASH (%) | 15 | 29 | 39 ** | 12 | 21 | 29 * |
1 All patients with baseline and week 96 biopsies
2 The 47 randomized and dosed patients who had missing biopsies at week 96 are treated as failures 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 (CMH))
“We believe today’s first-ever public report of reversal of cirrhosis due to MASH, whether by completer or ITT analysis, sets EFX apart from other approved or investigational treatments in the MASH landscape as a compound with transformational potential,” said Andrew Cheng, M.D., Ph.D., president and chief executive officer of Akero. “We look forward to continuing evaluation of 50mg EFX in our ongoing Phase 3 SYNCHRONY Outcomes study in patients with compensated cirrhosis due to MASH.”
The reversal of cirrhosis, as quantified by a consensus of two histopathologists, is supported by improvements in noninvasive measures of liver fibrosis and injury.
Summary of Week 96 Changes in Key Noninvasive Measures of Liver Fibrosis and Injury
| Measure (LS Mean Change From Baseline to Week 96) | Placebo (n=49) | 28mg (n=40-41) | 50mg (n=47) |
| ELF Score | +0.22 | -0.34 *** | -0.53 *** |
| Liver Stiffness (%) (FibroScan) | -8 | -18 | -24 * |
| ALT (U/L) | -6.8 | -10.5 | -11.1 |
| AST (U/L) | -1.6 | -8.1 | -11.2 ** |
* p<0.05, *** p<0.001, versus placebo (MMRM)
EFX was reported to be generally well-tolerated. There were no deaths on EFX, but one death in the placebo arm due to pneumonia. None of the Serious Adverse Events were determined to be related to study drug. Across both EFX groups, the most frequent adverse events (AEs) were grade 1 or 2, gastrointestinal in origin (diarrhea, nausea, and increased appetite) and transient in nature.
Conference Call / Webcast Details
Akero will host a conference call and webcast with slide presentation at 8:00 a.m. ET today. The live webcast will be available on the Events & Presentations page of Akero’s website, with the recording and presentation available immediately following the event.
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 eventually 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
The Phase 2b SYMMETRY study is a 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 enrolled a total of 182 patients, randomized to receive once-weekly subcutaneous dosing of 28mg or 50mg EFX, or placebo for 36 weeks, 181 of whom received at least one study dose. The primary efficacy endpoint for the study was the proportion of patients who achieve at least one-stage fibrosis improvement without worsening of MASH at week 36. Week 96 secondary measures included ≥1 stage fibrosis improvement and no worsening of MASH, MASH resolution, change from baseline in liver enzymes, noninvasive markers of liver fibrosis, glycemic control, and lipoproteins, as well as safety and tolerability measures.
About EFX
Efruxifermin (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 lipoprotein 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, EFX, is currently being evaluated in three ongoing Phase 3 clinical studies: SYNCHRONY Histology in patients with pre-cirrhotic MASH (F2-F3 fibrosis), SYNCHRONY Outcomes in patients with compensated cirrhosis 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 akerotx.com 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, including future plans or expectations for EFX and ongoing clinical studies, the therapeutic effects of EFX, as well as the dosing, safety and tolerability of EFX; and the future potential of EFX following the preliminary topline week 96 results of Akero’s Phase 2b SYMMETRY study, which are subject to audit and verification procedures and additional data that could result in material changes in the final data. 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 a clinical study 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 Tartaglia
Precision AQ
212.362.1200
christina.tartaglia@precisionaq.com
Media Contact:
Peg Rusconi
Deerfield Group
617.910.6217
Peg.rusconi@deerfieldgroup.com
FAQ
What were the main results of Akero's (AKRO) SYMMETRY Phase 2b study at Week 96?
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What were the safety results for EFX in Akero's (AKRO) Phase 2b SYMMETRY study?
How did non-GLP-1 patients respond to EFX treatment in AKRO's SYMMETRY trial?
