Sagimet Biosciences Announces Publication of Results from Phase 2b FASCINATE-2 Clinical Trial of Denifanstat in Biopsy-Confirmed F2/F3 MASH in The Lancet Gastroenterology & Hepatology
Sagimet Biosciences Inc. (Nasdaq: SGMT) announced the publication of results from their Phase 2b FASCINATE-2 clinical trial of denifanstat in The Lancet Gastroenterology & Hepatology. The trial, conducted on patients with biopsy-confirmed metabolic-dysfunction associated steatohepatitis (MASH) and stage 2 or 3 fibrosis, showed statistically significant and clinically meaningful improvements in disease activity, MASH resolution, and fibrosis.
Key findings include:
- 36% of denifanstat-treated patients achieved MASH resolution without worsening of fibrosis (vs 13% with placebo)
- 52% of denifanstat-treated patients showed ≥2-point reduction in NAS without worsening of fibrosis (vs 20% with placebo)
- 41% of denifanstat-treated patients demonstrated fibrosis improvement by ≥ 1 stage without worsening of steatohepatitis (vs 18% with placebo)
The results support the advancement of denifanstat into Phase 3 development, with Sagimet planning to start their Phase 3 program in 2024.
Sagimet Biosciences Inc. (Nasdaq: SGMT) ha annunciato la pubblicazione dei risultati del loro studio clinico di Fase 2b FASCINATE-2 riguardante denifanstat nella rivista The Lancet Gastroenterology & Hepatology. Lo studio, condotto su pazienti con steatoepatite metabolica associata a disfunzione (MASH) e fibrosi di stadio 2 o 3, ha mostrato miglioramenti statisticamente significativi e clinicamente rilevanti nell'attività della malattia, nella risoluzione del MASH e nella fibrosi.
I risultati chiave includono:
- Il 36% dei pazienti trattati con denifanstat ha raggiunto la risoluzione del MASH senza peggioramento della fibrosi (rispetto al 13% con placebo)
- Il 52% dei pazienti trattati con denifanstat ha mostrato una riduzione di ≥2 punti nel NAS senza peggioramento della fibrosi (rispetto al 20% con placebo)
- Il 41% dei pazienti trattati con denifanstat ha dimostrato un miglioramento della fibrosi di ≥ 1 stadio senza peggioramento della steatoepatite (rispetto al 18% con placebo)
I risultati supportano l'avanzamento del denifanstat nella fase di sviluppo Fase 3, con Sagimet che prevede di avviare il proprio programma di Fase 3 nel 2024.
Sagimet Biosciences Inc. (Nasdaq: SGMT) anunció la publicación de los resultados de su ensayo clínico de Fase 2b FASCINATE-2 sobre denifanstat en The Lancet Gastroenterology & Hepatology. El ensayo, realizado en pacientes con esteatohepatitis asociada a disfunción metabólica (MASH) y fibrosis de etapa 2 o 3, mostró mejoras estadísticamente significativas y clínicamente relevantes en la actividad de la enfermedad, la resolución del MASH y la fibrosis.
Los hallazgos clave incluyen:
- El 36% de los pacientes tratados con denifanstat alcanzó la resolución del MASH sin empeoramiento de la fibrosis (frente al 13% con placebo)
- El 52% de los pacientes tratados con denifanstat mostró una reducción de ≥2 puntos en el NAS sin empeoramiento de la fibrosis (frente al 20% con placebo)
- El 41% de los pacientes tratados con denifanstat demostró una mejoría de la fibrosis de ≥ 1 etapa sin empeoramiento de la esteatohepatitis (frente al 18% con placebo)
Los resultados respaldan el avance de denifanstat a la Fase 3 del desarrollo, con Sagimet planeando iniciar su programa de Fase 3 en 2024.
Sagimet Biosciences Inc. (Nasdaq: SGMT)는 denifanstat에 대한 2b상 FASCINATE-2 임상 시험 결과를 The Lancet Gastroenterology & Hepatology에 발표했다고 발표했습니다. 이 시험은 생검으로 확인된 대사 기능 장애 관련 지방간염 (MASH)과 2단계 또는 3단계의 섬유증 환자들을 대상으로 진행되었으며, 질병 활동, MASH 해결 및 섬유증에서 통계적으로 유의미하고 임상적으로 중요한 개선을 보였습니다.
주요 발견 사항은 다음과 같습니다:
- denifanstat 치료를 받은 환자의 36%가 섬유증 악화 없이 MASH 해결을 달성했습니다 (위약에 비해 13%)
- denifanstat 치료를 받은 환자의 52%가 섬유증 악화 없이 NAS에서 ≥2점 감소를 보였습니다 (위약에 비해 20%)
- denifanstat 치료를 받은 환자의 41%가 지방간염 악화 없이 섬유증 개선이 ≥ 1단계 발생했습니다 (위약에 비해 18%)
결과는 denifanstat이 3상 개발로 진행될 수 있음을 지지하며, Sagimet은 2024년에 3상 프로그램을 시작할 계획입니다.
Sagimet Biosciences Inc. (Nasdaq: SGMT) a annoncé la publication des résultats de leur essai clinique de Phase 2b FASCINATE-2 sur denifanstat dans The Lancet Gastroenterology & Hepatology. L'essai, mené sur des patients avec une stéatohépatite associée à une dysfonction métabolique (MASH) confirmée par biopsie et présentant une fibrose au stade 2 ou 3, a montré des améliorations statistiquement significatives et cliniquement pertinentes de l'activité de la maladie, de la résolution du MASH et de la fibrose.
Les résultats clés incluent :
- 36 % des patients traités par denifanstat ont atteint la résolution du MASH sans aggravation de la fibrose (contre 13 % avec le placebo)
- 52 % des patients traités par denifanstat ont montré une réduction de ≥2 points dans le NAS sans aggravation de la fibrose (contre 20 % avec le placebo)
- 41 % des patients traités par denifanstat ont démontré une amélioration de la fibrose d'au moins 1 stade sans aggravation de la stéatohépatite (contre 18 % avec le placebo)
Les résultats soutiennent l'avancement de denifanstat dans le développement de la Phase 3, Sagimet prévoyant de lancer son programme de Phase 3 en 2024.
Sagimet Biosciences Inc. (Nasdaq: SGMT) hat die Veröffentlichung der Ergebnisse ihrer Phase 2b FASCINATE-2-Studie zu denifanstat in The Lancet Gastroenterology & Hepatology bekannt gegeben. Die Studie wurde an Patienten mit durch Biopsie bestätigter metabolisch bedingter Steatohepatitis (MASH) und Fibrose des Stadiums 2 oder 3 durchgeführt und zeigte statistisch signifikante und klinisch relevante Verbesserungen in der Krankheitsaktivität, der MASH-Resolution und der Fibrose.
Wichtige Ergebnisse sind:
- 36% der mit denifanstat behandelten Patienten erreichten eine MASH-Resolution ohne Verschlechterung der Fibrose (gegenüber 13% mit Placebo)
- 52% der mit denifanstat behandelten Patienten zeigten eine ≥2-Punkte-Reduktion im NAS ohne Verschlechterung der Fibrose (gegenüber 20% mit Placebo)
- 41% der mit denifanstat behandelten Patienten zeigten eine Verbesserung der Fibrose um ≥ 1 Stadium ohne Verschlechterung der Steatohepatitis (gegenüber 18% mit Placebo)
Die Ergebnisse unterstützen den Fortschritt von denifanstat in die Phase 3 Entwicklung, wobei Sagimet plant, 2024 mit seinem Phase 3 Programm zu beginnen.
- Statistically significant improvement in MASH resolution without worsening of fibrosis (36% vs 13% placebo, p=0.0044)
- Significant reduction in NAS score without worsening of fibrosis (52% vs 20% placebo, p=0.0003)
- Fibrosis improvement by ≥ 1 stage without worsening of steatohepatitis (41% vs 18% placebo, p=0.0103)
- 49% of F3 fibrosis patients showed fibrosis improvement (vs 13% placebo, p=0.0032)
- No treatment-related serious adverse events observed
- Results support advancement to Phase 3 development
- Slight increase in triglyceride levels by week 52 in denifanstat-treated patients
Insights
The Phase 2b FASCINATE-2 trial results for denifanstat in MASH patients are highly encouraging. Key findings include:
- 36% of denifanstat-treated patients achieved MASH resolution without worsening fibrosis vs 13% with placebo (p=0.0044)
- 52% showed ≥2-point NAS reduction without worsening fibrosis vs 20% with placebo (p=0.0003)
- 41% demonstrated fibrosis improvement without worsening steatohepatitis vs 18% with placebo (p=0.0103)
- Significant improvements in F3 fibrosis patients: 49% vs 13% (p=0.0032)
These results suggest denifanstat's potential to address multiple aspects of MASH pathology, including fat accumulation, inflammation and fibrosis. The drug's safety profile appears favorable, with no treatment-related serious adverse events. The data support advancing to Phase 3 trials, positioning Sagimet well in the competitive MASH treatment landscape.
This clinical trial data represents a significant milestone for Sagimet Biosciences, potentially increasing the company's value proposition. Key financial implications include:
- Increased probability of successful Phase 3 trials and eventual FDA approval
- Enhanced attractiveness for potential partnerships or licensing deals
- Possible increase in investor interest and stock valuation
- Potential for expanded market opportunity in MASH treatment
With a market cap of
- Treatment with denifanstat achieved statistically significant and clinically meaningful improvements in disease activity, MASH resolution and fibrosis -
- Results support advancement of denifanstat into Phase 3 development -
SAN MATEO, Calif., Oct. 11, 2024 (GLOBE NEWSWIRE) -- Sagimet Biosciences Inc. (Sagimet, Nasdaq: SGMT), a clinical-stage biopharmaceutical company developing novel fatty acid synthase (FASN) inhibitors designed to target dysfunctional metabolic and fibrotic pathways, today announced that results from the Phase 2b FASCINATE-2 clinical trial of denifanstat versus placebo in biopsy-confirmed metabolic-dysfunction associated steatohepatitis (MASH) patients with stage 2 or stage 3 fibrosis (F2/F3) were published in The Lancet Gastroenterology & Hepatology.
The publication, “Denifanstat for the treatment of Metabolic-dysfunction Associated Steatohepatitis: a multicentre, double-blind, randomised, placebo-controlled, ph2b trial,” reported that treatment with denifanstat achieved statistically significant and clinically meaningful improvements in disease activity, MASH resolution and fibrosis.
“Patients living with MASH, a complex disease, urgently need treatments that simultaneously address the three main drivers of liver injury: fat accumulation, inflammation, and fibrosis,” said Rohit Loomba, M.D., M.H.Sc., Professor of Medicine, Chief, Division of Gastroenterology and Hepatology, and Director, MASLD Research Center, University of California San Diego, the primary investigator of the FASCINATE-2 trial and lead author of The Lancet Gastroenterology & Hepatology paper. “These data support denifanstat’s potential to improve overall liver health by targeting the major pathways responsible for liver injury. Results of the current study include the improvement in fibrosis without worsening of MASH in
The publication reports that denifanstat showed statistically significant improvements at week 52 relative to placebo on both of the primary endpoints: MASH resolution without worsening of fibrosis with ≥2-point reduction in NAS (
Dave Happel, Chief Executive Officer of Sagimet, commented, “Our publication in this esteemed Lancet journal validates the importance of these findings and reinforces the potential impact of denifanstat, our oral fat synthesis inhibitor, to improve patient outcomes, particularly as the disease becomes more severe. The data demonstrate significant improvements in all key histological features of the disease, meeting both fibrosis improvement and MASH resolution endpoints as outlined in the FDA draft guidance for Phase 3 clinical trials in MASH. We look forward to building on the encouraging data generated to date which supports the advancement of denifanstat into Phase 3 development. We are committed to addressing the urgent needs of patients living with MASH and anticipate starting our planned Phase 3 program in 2024.”
Denifanstat also demonstrated statistically significant results on multiple secondary endpoints. Consistent with denifanstat’s ability to directly block fibrogenesis by stellate cells, a statistically significant fibrosis response rate was observed by both traditional pathology and AI-based digital pathology, including in patients with advanced disease.
- Secondary histology endpoints:
- Fibrosis improvement by ≥ 1 stage without worsening of steatohepatitis was observed in
41% denifanstat-treated patients vs18% with placebo (p=0.0103). Further, fibrosis improvement by ≥ 2 stages without worsening of steatohepatitis was observed in20% denifanstat-treated patients vs2% with placebo (p=0.0065). Fibrosis improvement by ≥ 1 stage without worsening of steatohepatitis was observed in specific patient subsets as follows:- F3 fibrosis:
49% with denifanstat vs13% with placebo (p=0.0032). - Type 2 diabetes:
40% with denifanstat vs19% with placebo (p=0.076). - Patients on stable background of glucagon-like peptide 1 receptor agonists:
42% with denifanstat vs0% with placebo (p=0.034).
- F3 fibrosis:
- MASH resolution with no worsening of fibrosis was observed in
38% of denifanstat-treated patients vs16% with placebo (p=0.0043). - Achievement of both MASH resolution and fibrosis improvement in the same patient was observed in
24% of denifanstat-treated patients vs7% with placebo (p=0.013).
- Fibrosis improvement by ≥ 1 stage without worsening of steatohepatitis was observed in
- Non-invasive biomarkers of liver health:
- Improvements in liver and metabolic health measurements were observed with denifanstat treatment, including decreases in liver fat by MRI-PDFF imaging, and decreases in liver enzymes and other hepatic markers.
- Despite the concurrent use of statins in over half the study patients, LDL-cholesterol was reduced with denifanstat treatment, notably in patients with a baseline level ≥100mg/dL. Triglyceride (TG) levels increased slightly by week 52 in denifanstat-treated patients, driven by an increase in polyunsaturated and decreased saturated fatty acid content, which can be associated with cardiovascular health.
- Safety: As in prior studies, no treatment-related serious adverse events (SAEs) were observed, and the majority of adverse events (AEs) were mild to moderate in nature (Grades 1 and 2). There were no Grade ≥3 treatment-related AEs and no drug-induced liver injury (DILI) signal in the study.
About Phase 2b FASCINATE-2 Clinical Trial
The Phase 2b FASCINATE-2 clinical trial was a 52-week randomized, double-blind, placebo-controlled trial that evaluated the safety and histological impact of denifanstat compared to placebo in 168 biopsy-confirmed MASH patients with moderate-to-severe fibrosis (stage F2 or F3) with NAS ≥4. Patients were randomized 2:1 to receive 50 mg denifanstat or placebo, taken orally once daily. An end-of-trial biopsy was assessed by a central pathologist for histological endpoints. Liver biopsies were also analyzed using AI-based digital pathology.
About Sagimet Biosciences
Sagimet is a clinical-stage biopharmaceutical company developing novel fatty acid synthase (FASN) inhibitors that are designed to target dysfunctional metabolic and fibrotic pathways in diseases resulting from the overproduction of the fatty acid, palmitate. Sagimet’s lead drug candidate, denifanstat, is an oral, once-daily pill and selective FASN inhibitor in development for the treatment of MASH. FASCINATE-2, a Phase 2b clinical trial of denifanstat in MASH with liver biopsy-based primary endpoints, was successfully completed with positive results. In September 2024, the FDA granted Breakthrough Therapy designation to denifanstat for the treatment of noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH) with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis). For additional information about Sagimet, please visit www.sagimet.com.
About MASH
MASH is a progressive and severe liver disease which is estimated to impact more than 115 million people worldwide, for which there is only one recently approved treatment in the United States and no currently approved treatments in Europe. In 2023, global liver disease medical societies and patient groups formalized the decision to rename non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated steatotic liver disease (MASLD) and nonalcoholic steatohepatitis (NASH) to metabolic dysfunction-associated steatohepatitis (MASH). Additionally, an overarching term, steatotic liver disease (SLD), was established to capture multiple types of liver diseases associated with fat buildup in the liver. The goal of the name change was to establish an affirmative, non-stigmatizing name and diagnosis.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of, and made pursuant to the safe harbor provisions of, The Private Securities Litigation Reform Act of 1995. All statements contained in this press release, other than statements of historical facts or statements that relate to present facts or current conditions, including but not limited to, statements regarding: the expected timing of the presentation of data from ongoing clinical trials, Sagimet’s clinical development plans and related anticipated development milestones, Sagimet’s cash and financial resources and expected cash runway. These statements involve known and unknown risks, uncertainties and other important factors that may cause Sagimet’s actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. In some cases, these statements can be identified by terms such as “may,” “might,” “will,” “should,” “expect,” “plan,” “aim,” “seek,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “forecast,” “potential” or “continue” or the negative of these terms or other similar expressions.
The forward-looking statements in this press release are only predictions. Sagimet has based these forward-looking statements largely on its current expectations and projections about future events and financial trends that Sagimet believes may affect its business, financial condition and results of operations. These forward-looking statements speak only as of the date of this press release and are subject to a number of risks, uncertainties and assumptions, some of which cannot be predicted or quantified and some of which are beyond Sagimet’s control, including, among others: the clinical development and therapeutic potential of denifanstat or any other drug candidates Sagimet may develop; Sagimet’s ability to advance drug candidates into and successfully complete clinical trials within anticipated timelines, including its Phase 3 denifanstat program; Sagimet’s relationship with Ascletis, and the success of its development efforts for denifanstat; the accuracy of Sagimet’s estimates regarding its capital requirements; and Sagimet’s ability to maintain and successfully enforce adequate intellectual property protection. These and other risks and uncertainties are described more fully in the “Risk Factors” section of Sagimet’s most recent filings with the Securities and Exchange Commission and available at www.sec.gov. You should not rely on these forward-looking statements as predictions of future events. The events and circumstances reflected in these forward-looking statements may not be achieved or occur, and actual results could differ materially from those projected in the forward-looking statements. Moreover, Sagimet operates in a dynamic industry and economy. New risk factors and uncertainties may emerge from time to time, and it is not possible for management to predict all risk factors and uncertainties that Sagimet may face. Except as required by applicable law, Sagimet does not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise.
Contact:
Joyce Allaire
LifeSci Advisors
JAllaire@lifesciadvisors.com
FAQ
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