MetaVia Announces Positive Top-Line Results From Its Phase 2a Clinical Trial of DA-1241 in Patients with Presumed MASH
MetaVia (NASDAQ: MTVA) announced positive top-line results from its Phase 2a clinical trial of DA-1241 in patients with presumed metabolic dysfunction-associated steatohepatitis (MASH). The trial demonstrated that DA-1241 (100mg) achieved statistically significant reduction in ALT levels at weeks 4 and 8, with near-significant reduction at week 16.
Key findings include statistically significant improvements in CAP Score and HbA1c levels at Week 16. The drug showed strong safety profile with mostly mild adverse events and no drug-related serious adverse events. The study involved 109 randomized patients across two parts: testing DA-1241 alone and in combination with sitagliptin.
MetaVia (NASDAQ: MTVA) ha annunciato risultati positivi dalla sua sperimentazione clinica di Fase 2a di DA-1241 in pazienti con steatoepatite metafunzionante associata a disfunzione metabolica (MASH). Lo studio ha dimostrato che DA-1241 (100mg) ha conseguito una riduzione statisticamente significativa dei livelli di ALT alle settimane 4 e 8, con una riduzione quasi significativa alla settimana 16.
I risultati chiave includono miglioramenti statisticamente significativi nel punteggio CAP e nei livelli di HbA1c alla settimana 16. Il farmaco ha mostrato un forte profilo di sicurezza con eventi avversi per lo più lievi e nessun evento avverso grave legato al farmaco. Lo studio ha coinvolto 109 pazienti randomizzati in due fasi: testando DA-1241 da solo e in combinazione con sitagliptin.
MetaVia (NASDAQ: MTVA) anunció resultados positivos de su ensayo clínico de Fase 2a sobre DA-1241 en pacientes con esteatosis hepática asociada a disfunción metabólica presunta (MASH). El ensayo demostró que DA-1241 (100mg) logró una reducción estadísticamente significativa de los niveles de ALT en las semanas 4 y 8, con una reducción casi significativa en la semana 16.
Los hallazgos clave incluyen mejoras estadísticamente significativas en el puntaje CAP y los niveles de HbA1c en la semana 16. El fármaco mostró un perfil de seguridad sólido con eventos adversos mayormente leves y ningún evento adverso grave relacionado con el medicamento. El estudio involucró a 109 pacientes aleatorizados en dos partes: probando DA-1241 solo y en combinación con sitagliptina.
메타비아 (NASDAQ: MTVA)는 대사 기능 장애와 관련된 지방간염 (MASH) 환자를 대상으로 한 DA-1241의 2a상 임상 시험에서 긍정적인 상위 결과를 발표했습니다. 이 시험에서 DA-1241 (100mg)은 4주 및 8주차에 ALT 수치의 통계적으로 유의미한 감소를 달성했으며, 16주차에는 거의 유의미한 감소를 보였습니다.
주요 발견 사항으로는 16주차에 CAP 점수와 HbA1c 수치의 통계적으로 유의미한 개선이 포함됩니다. 이 약물은 대부분 경미한 유해 사건으로 부작용 프로필이 양호하며, 약물과 관련된 심각한 유해 사건은 없었습니다. 연구에는 두 가지 부분에서 109명의 무작위 환자가 참여했으며, DA-1241을 단독으로 및 시타글립틴과 병용하여 테스트했습니다.
MetaVia (NASDAQ: MTVA) a annoncé des résultats positifs issus de son essai clinique de phase 2a sur DA-1241 chez des patients présentant une stéatopathie métabolique associée à une dysfonction métabolique présumée (MASH). L'essai a démontré que DA-1241 (100 mg) a obtenu une réduction statistiquement significative des niveaux d'ALT aux semaines 4 et 8, avec une réduction presque significative à la semaine 16.
Les résultats clés comprennent des améliorations statistiquement significatives du score CAP et des niveaux d'HbA1c à la semaine 16. Le médicament a montré un bon profil de sécurité avec principalement des événements indésirables légers et aucun événement indésirable grave lié au médicament. L'étude a impliqué 109 patients randomisés en deux parties : test de DA-1241 seul et en combinaison avec la sitagliptine.
MetaVia (NASDAQ: MTVA) gab positive Zwischenergebnisse aus seiner Phase 2a-Studie zu DA-1241 bei Patienten mit vermuteter metabolischer Dysfunktion-assoziierter Steatohepatitis (MASH) bekannt. Die Studie zeigte, dass DA-1241 (100mg) eine statistisch signifikante Reduktion der ALT-Werte in den Wochen 4 und 8 erzielte, mit einer nahezu signifikanten Reduktion in Woche 16.
Zu den wichtigsten Ergebnissen gehören statistisch signifikante Verbesserungen in der CAP-Punktzahl und den HbA1c-Werten in Woche 16. Das Medikament zeigte ein starkes Sicherheitsprofil mit überwiegend milden unerwünschten Ereignissen und keinen schwerwiegenden durch das Medikament verursachten unerwünschten Ereignissen. Die Studie umfasste 109 randomisierte Patienten in zwei Teilen: Testung von DA-1241 allein und in Kombination mit Sitagliptin.
- DA-1241 100mg achieved statistically significant ALT reductions at weeks 4 (p=0.0159) and 8 (p=0.0342)
- Significant improvements in CAP score at Week 16 for DA-1241 100mg (p=0.0308)
- Significant HbA1c reductions at Week 16 for DA-1241 100mg (p=0.0179)
- Strong safety profile with mostly mild adverse events and no drug-related SAEs
- DA-1241 50mg showed significant improvement in ALT normalization (odds ratio 10.500, p=0.0487)
- ALT reduction at week 16 missed statistical significance (p=0.0506)
- Small study size may limit result interpretation
Insights
- DA-1241 Demonstrated Direct Hepatic Action in Addition to Its Glucose Lowering Effect
- Patients Treated with DA-1241 100mg Achieved Statistically Significant Reduction in ALT Levels at Weeks 4 and 8, and a Near Statistically Significant Reduction at Week 16
- DA-1241 100mg Demonstrated Statistically Significant Improvements in CAP Score at Week 16
- DA-1241 100mg Showed Statistically Significant Reductions in HbA1C at Week 16
- DA-1241 was Very Well Tolerated
- Awaiting Data on Other Exploratory Endpoints Including MRI-PDFF
- Additional Findings to be Submitted for Upcoming Scientific Conferences
Primary Efficacy Endpoint
LS Mean ALT Changes from Baseline (U/L)
Placebo (N=23) | DA-1241 100mg + (N=34) | P value vs. | DA-1241 50mg (N=12) | P value vs. | DA-1241 100mg (N=22) | P value vs. | |
Baseline Mean | 68.4 | 63.2 | 65.8 | 57.2 | |||
Week 4 LS Mean ( | -1.51 (-8.23, 5.21) | -8.38 (-13.89, -2.87)* | 0.1195 | -9.63 (-18.90, -0.35)* | 0.1622 | -13.44 (-20.32, -6.57)* | 0.0159† |
Week 8 LS Mean ( | 0.13 (-7.83, 8.09) | -10.27 (-16.80, -3.73)* | 0.0479† | -11.05 (-22.04, -0.05)* | 0.1050 | -12.25 (-20.40, -4.10)* | 0.0342† |
Week 16 LS Mean ( | -4.70 (-14.05, 4.65) | -8.24 (-15.91, -0.57)* | 0.5624 | -16.81 (-29.72, -3.89)* | 0.1345 | -18.09 (-27.67, -8.52)* | 0.0506 |
* Confidence interval excludes 0, suggesting a statistically meaningful difference. |
Notable Secondary Endpoints
Proportion of Subjects with Normalized ALT <30 IU/L at Week 16
Placebo (N=23) | DA-1241 100mg + (N=34) | DA-1241 50mg (N=12) | DA-1241 100mg (N=22) | |
Number of Subjects, n | ||||
< 30, n (%) | 1 (4.3 %) | 3 (8.8 %) | 4 (33.3 %) | 4 (18.2 %) |
Odds Ratio (p value) | 2.423 (0.4576) | 10.500 (0.0487)† | 5.600 (0.1402) |
† p < 0.05 vs. placebo |
LS Mean CAP, VCTE, FAST score Changes from Baseline at Week 16
Placebo (N=23) | DA-1241 100mg (N=34) | P value vs. | DA-1241 50mg (N=12) | P value vs. | DA-1241 100mg (N=22) | P value vs. | |
Baseline Mean (dB/m) | 347.4 | 344.1 | 347.3 | 336.0 | |||
Week 16 LS Mean CAP Score (dB/m) ( | -2.32 (-16.17, 11.52) | -20.62 (-31.99, -9.26)* | 0.0452† | -8.94 (-28.08, 10.20) | 0.5787 | -24.32 (-38.54, -10.10)* | 0.0308† |
Baseline Mean (kPa) | 10.00 | 9.89 | 10.71 | 10.32 | |||
Week 16 LS Mean VCTE Score (kPa) ( | 0.29 (-1.31, 1.89) | -1.45 (-2.77, -0.13)* | 0.0997 | -1.40 (-3.62, 0.83) | 0.2257 | 0.00 (-1.64, 1.64) | 0.8051 |
Baseline Mean | 0.555 | 0.564 | 0.604 | 0.538 | |||
Week 16 LS Mean FAST score ( | -0.09 (-0.17, -0.01)* | -0.19 (-0.26, -0.13)* | 0.0416† | -0.17 (-0.28, -0.06)* | 0.2429 | -0.19 (-0.27, -0.11)* | 0.0704 |
* Confidence interval excludes 0, suggesting a statistically meaningful difference. |
LS Mean HbA1C Changes from Baseline at Week 16 (%)
Placebo (N=23) | DA-1241 100mg (N=34) | P value vs. | DA-1241 50mg (N=12) | P value vs. | DA-1241 100mg (N=22) | P value vs. | |
Baseline Mean | 6.78 | 6.51 | 6.58 | 7.01 | |||
Week 16 LS Mean ( | -0.10 (-0.23, 0.44) | -0.52 (-0.80, -0.25)* | 0.0050† | -0.24 (-0.70, 0.22) | 0.2357 | -0.48 (-0.82, -0.13) * | 0.0179† |
* Confidence interval excludes 0, suggesting a statistically meaningful difference. |
Overall TEAE Summary
N (%) | Placebo (N=32) | DA-1241 (N=36) | DA-1241 50mg (N=14) | DA-1241 100mg (N=26) |
Subjects with any Treatment Related AE Mild Moderate Severe | 9 ( 8 ( 1 ( 0 | 10 ( 9 ( 1 ( 0 | 4 ( 4 ( 0 0 | 9 ( 8 ( 1 ( 0 |
Subjects with any Treatment related SAE | 0 | 0 | 0 | 0 |
Subjects with any TEAE leading to study discontinuation | 0 | 1 ( 3.1 %) | 0 | 0 |
Subjects with any TEAE leading to study drug discontinuation | 1 ( 3.1 %) | 0 | 0 | 0 |
- DA-1241 100mg showed statistically significant reductions in ALT levels at weeks 4 and 8 (p=0.0159 and p=0.0342, respectively) and a near statistically significant reduction (p=0.0506) at week 16 compared to placebo.
- DA-1241 50mg showed a statistically significant improvement in the normalization of ALT levels compared to placebo, with an odds ratio of 10.500 (p=0.0487).
- DA-1241 100mg and DA-1241 100mg + Sitagliptin 100mg showed significant improvements in the CAP score compared to placebo (p=0.0308 and p=0.0452, respectively).
- DA-1241 100mg + Sitagliptin 100mg showed a statistically significant reduction in the FAST score compared to placebo (p=0.0416).
- DA-1241 100mg and DA-1241 100mg + Sitagliptin 100mg showed significant reductions in HbA1C from baseline at Week 16 compared to the placebo group (p=0.0179 and p=0.0050, respectively).
"Achieving the primary endpoint of a reduction in ALT levels through direct hepatic effects, as well as notable secondary endpoints, including significantly lower HbA1C levels compared to the placebo, are extremely positive results for DA-1241, especially given the small study size," stated Hyung Heon Kim, President and Chief Executive Officer of MetaVia. "Importantly, DA-1241 was shown to be very well tolerated with mostly mild AEs and no drug related SAEs in the treatment groups. Based on this data, we continue to believe that the novel mechanism of action of DA-1241, addressing the inflammation linked to MASH, will result in a safe and effective treatment option for this disease. We continue to conduct pre-clinical studies to explore other combination therapies for DA-1241, which may provide additional benefits to treat patients along the full spectrum on MASH. We look forward to the full data set and expect to have an end of Phase 2 meeting with the
Each of the two parts of the Phase 2a trial of DA-1241 were designed to be 16-week, multicenter, randomized, double-blind, placebo-controlled, parallel clinical studies to evaluate the efficacy and safety of DA-1241 in subjects with presumed MASH. A total of 109 patients were randomized, while 95 patients completed the dosing. These patients were enrolled in either Part 1, which is exploring the efficacy of DA-1241 versus placebo, and randomized in a 1:2:1 ratio into 3 treatment groups: DA-1241 50 mg, DA-1241 100mg or placebo, or into Part 2, which is exploring the efficacy of DA-1241 in combination with sitagliptin versus placebo, randomized in a 2:1 ratio into 2 treatment groups: DA-1241 100mg/sitagliptin 100mg or placebo. For both Part 1 and Part 2, the primary endpoint is the change from baseline in alanine transaminase (ALT) levels at Week 16.
For more information on this clinical trial, please visit: www.clinicaltrials.gov NCT06054815.
About DA-1241
DA-1241 is a novel G-Protein-Coupled Receptor 119 (GPR119) agonist with development optionality as a standalone and/or combination therapy for both MASH and type 2 diabetes (T2D). Agonism of GPR119 in the gut promotes the release of key gut peptides GLP-1, GIP, and PYY. These peptides play a further role in glucose metabolism, lipid metabolism and weight loss. DA-1241 has beneficial effects on glucose, lipid profile and liver inflammation, supported by potential efficacy demonstrated during in vivo preclinical studies. The therapeutic potential of DA-1241 has been demonstrated in multiple pre-clinical animal models of MASH and T2D where DA-1241 reduced hepatic steatosis, inflammation, fibrosis, and improved glucose control. Furthermore, in Phase 1a and 1b trials, DA-1241 was well tolerated in both healthy volunteers and those with T2DM.
About MetaVia
MetaVia Inc. is a clinical-stage biotechnology company focused on transforming cardiometabolic diseases. The company is currently developing DA-1726 for the treatment of obesity, and is developing DA-1241 for the treatment of Metabolic Dysfunction-Associated Steatohepatitis (MASH). DA-1726 is a novel oxyntomodulin (OXM) analogue that functions as a glucagon-like peptide-1 receptor (GLP1R) and glucagon receptor (GCGR) dual agonist. OXM is a naturally-occurring gut hormone that activates GLP1R and GCGR, thereby decreasing food intake while increasing energy expenditure, thus potentially resulting in superior body weight loss compared to selective GLP1R agonists. DA-1241 is a novel G-protein-coupled receptor 119 (GPR119) agonist that promotes the release of key gut peptides GLP-1, GIP, and PYY. In pre-clinical studies, DA-1241 demonstrated a positive effect on liver inflammation, lipid metabolism, weight loss, and glucose metabolism, reducing hepatic steatosis, hepatic inflammation, and liver fibrosis, while also improving glucose control.
For more information, please visit www.metaviatx.com.
Forward Looking Statements
Certain statements in this press release may be considered forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "believes", "expects", "anticipates", "may", "will", "should", "seeks", "approximately", "potential", "intends", "projects", "plans", "estimates" or the negative of these words or other comparable terminology (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. Forward-looking statements are predictions, projections and other statements about future events that are based on current expectations and assumptions and, as a result, are subject to risks and uncertainties. Many factors could cause actual future events to differ materially from the forward-looking statements in this press release, including, without limitation, those risks associated with MetaVia's ability to execute on its commercial strategy; the timeline for regulatory submissions; the ability to obtain regulatory approval through the development steps of MetaVia's current and future product candidates; the ability to realize the benefits of the license agreement with Dong-A ST Co. Ltd., including the impact on future financial and operating results of MetaVia; the cooperation of MetaVia's contract manufacturers, clinical study partners and others involved in the development of MetaVia's current and future product candidates; potential negative interactions between MetaVia's product candidates and any other products with which they are combined for treatment; MetaVia's ability to initiate and complete clinical trials on a timely basis; MetaVia's ability to recruit subjects for its clinical trials; whether MetaVia receives results from MetaVia's clinical trials that are consistent with the results of pre-clinical and previous clinical trials; impact of costs related to the license agreement, known and unknown, including costs of any litigation or regulatory actions relating to the license agreement; the effects of changes in applicable laws or regulations; the effects of changes to MetaVia's stock price on the terms of the license agreement and any future fundraising; and other risks and uncertainties described in MetaVia's filings with the Securities and Exchange Commission, including MetaVia's most recent Annual Report on Form 10-K. Forward-looking statements speak only as of the date when made. MetaVia does not assume any obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.
Contacts:
MetaVia
Marshall H. Woodworth
Chief Financial Officer
+1-857-299-1033
marshall.woodworth@metaviatx.com
Rx Communications Group
Michael Miller
+1-917-633-6086
mmiller@rxir.com
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SOURCE MetaVia Inc.
FAQ
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