Altimmune Announces Positive Topline Results from the IMPACT Phase 2b Trial of Pemvidutide in the Treatment of MASH
Altimmune (NASDAQ:ALT) announced positive topline results from its IMPACT Phase 2b trial of pemvidutide for metabolic dysfunction-associated steatohepatitis (MASH). The trial, involving 212 participants, demonstrated significant efficacy with up to 59.1% achieving MASH resolution without worsening of fibrosis at 24 weeks. The study showed weight loss of up to 6.2% with no plateauing and liver fat reductions of up to 62.8%.
The drug exhibited exceptional tolerability with less than 1% treatment discontinuations due to adverse events in pemvidutide-treated participants. The 1.2mg and 1.8mg doses demonstrated statistically significant improvements across multiple endpoints compared to placebo, including non-invasive tests of fibrosis. A supplemental AI-based analysis showed 30.6% of participants receiving pemvidutide 1.8mg achieved a 60% or greater reduction in fibrosis.
Altimmune (NASDAQ:ALT) ha annunciato risultati positivi preliminari dal suo studio di fase 2b IMPACT su pemvidutide per la steatoepatite associata a disfunzione metabolica (MASH). Lo studio, che ha coinvolto 212 partecipanti, ha mostrato un'efficacia significativa con fino al 59,1% dei pazienti che hanno raggiunto la risoluzione della MASH senza peggioramento della fibrosi a 24 settimane. È stata osservata una perdita di peso fino al 6,2% senza plateau e una riduzione del grasso epatico fino al 62,8%.
Il farmaco ha dimostrato un'eccezionale tollerabilità con meno dell'1% di interruzioni del trattamento dovute ad eventi avversi nei pazienti trattati con pemvidutide. Le dosi da 1,2 mg e 1,8 mg hanno mostrato miglioramenti statisticamente significativi su vari parametri rispetto al placebo, inclusi test non invasivi della fibrosi. Un'analisi supplementare basata su IA ha evidenziato che il 30,6% dei partecipanti che hanno ricevuto pemvidutide 1,8 mg ha ottenuto una riduzione della fibrosi pari o superiore al 60%.
Altimmune (NASDAQ:ALT) anunció resultados positivos preliminares de su ensayo IMPACT de fase 2b con pemvidutide para la esteatohepatitis asociada a disfunción metabólica (MASH). El ensayo, que incluyó a 212 participantes, demostró una eficacia significativa con hasta un 59.1% logrando la resolución de MASH sin empeoramiento de la fibrosis a las 24 semanas. El estudio mostró una pérdida de peso de hasta el 6.2% sin estancamiento y una reducción de grasa hepática de hasta el 62.8%.
El medicamento presentó una tolerabilidad excepcional con menos del 1% de discontinuaciones del tratamiento debido a eventos adversos en los participantes tratados con pemvidutide. Las dosis de 1.2 mg y 1.8 mg mostraron mejoras estadísticamente significativas en múltiples parámetros comparados con placebo, incluyendo pruebas no invasivas de fibrosis. Un análisis adicional basado en IA mostró que el 30.6% de los participantes que recibieron pemvidutide 1.8 mg lograron una reducción del 60% o más en fibrosis.
Altimmune (NASDAQ:ALT)는 대사 기능 장애 관련 지방간염(MASH)에 대한 펨비두타이드 임팩트(IMPACT) 2b상 시험에서 긍정적인 주요 결과를 발표했습니다. 212명의 참가자가 포함된 이번 시험에서 24주 후 최대 59.1%가 MASH 완화를 달성했으며 섬유증 악화 없이 유의미한 효능을 보였습니다. 연구에서는 체중이 최대 6.2% 감소했고, 체중 감소가 멈추지 않았으며 간 지방은 최대 62.8% 감소했습니다.
이 약물은 펨비두타이드 치료군에서 부작용으로 인한 치료 중단율이 1% 미만으로 탁월한 내약성을 나타냈습니다. 1.2mg 및 1.8mg 용량은 위약 대비 여러 평가 지표에서 통계적으로 유의한 개선을 보여주었으며, 비침습적 섬유증 검사도 포함됩니다. 인공지능 보조 분석 결과, 1.8mg 펨비두타이드를 투여받은 참가자의 30.6%가 섬유증을 60% 이상 감소시켰습니다.
Altimmune (NASDAQ:ALT) a annoncé des résultats positifs préliminaires de son essai de phase 2b IMPACT évaluant le pemvidutide pour la stéatohépatite associée à une dysfonction métabolique (MASH). L'essai, impliquant 212 participants, a démontré une efficacité significative avec jusqu'à 59,1% des patients ayant obtenu la résolution de la MASH sans aggravation de la fibrose à 24 semaines. L'étude a montré une perte de poids allant jusqu'à 6,2% sans plateau et une réduction de la graisse hépatique allant jusqu'à 62,8%.
Le médicament a présenté une tolérance exceptionnelle avec moins de 1% d'arrêt du traitement en raison d'événements indésirables chez les participants traités par pemvidutide. Les doses de 1,2 mg et 1,8 mg ont montré des améliorations statistiquement significatives sur plusieurs critères par rapport au placebo, incluant des tests non invasifs de la fibrose. Une analyse supplémentaire basée sur l'IA a révélé que 30,6% des participants recevant 1,8 mg de pemvidutide ont obtenu une réduction de la fibrose de 60% ou plus.
Altimmune (NASDAQ:ALT) hat positive Zwischenergebnisse aus der IMPACT Phase-2b-Studie mit Pemvidutide bei metabolisch bedingter Steatohepatitis (MASH) bekanntgegeben. Die Studie mit 212 Teilnehmern zeigte eine signifikante Wirksamkeit mit bis zu 59,1% der Patienten, die eine MASH-Auflösung ohne Verschlechterung der Fibrose nach 24 Wochen erreichten. Es wurde ein Gewichtsverlust von bis zu 6,2% ohne Plateau und eine Reduktion des Leberfetts um bis zu 62,8% beobachtet.
Das Medikament zeigte eine hervorragende Verträglichkeit mit weniger als 1% Behandlungsabbrüchen aufgrund von Nebenwirkungen bei den mit Pemvidutide behandelten Teilnehmern. Die Dosierungen von 1,2 mg und 1,8 mg zeigten im Vergleich zu Placebo statistisch signifikante Verbesserungen bei mehreren Endpunkten, einschließlich nicht-invasiver Fibrosetests. Eine ergänzende KI-basierte Analyse ergab, dass 30,6% der Teilnehmer, die 1,8 mg Pemvidutide erhielten, eine Fibrose-Reduktion von 60% oder mehr erzielten.
- MASH resolution achieved in up to 59.1% of participants without worsening of fibrosis
- Significant weight loss of up to 6.2% at 24 weeks with no plateauing
- Exceptional safety profile with less than 1% treatment discontinuations
- Liver fat reductions of up to 62.8% in treated participants
- Strong anti-fibrotic activity demonstrated through AI-based analysis
- Statistically significant improvements in non-invasive fibrosis tests
- Fibrosis improvement endpoint did not reach statistical significance in primary analysis
- Composite endpoint of MASH resolution and fibrosis improvement not statistically significant
Insights
Altimmune's pemvidutide shows remarkable MASH resolution, weight loss, and safety profile, positioning it as a potential best-in-class therapeutic.
The IMPACT Phase 2b trial results for pemvidutide represent a significant clinical breakthrough in MASH treatment. The most impressive finding is the 59.1% MASH resolution rate without worsening fibrosis at the 1.2 mg dose compared to just 19.1% for placebo (p<0.0001). This primary endpoint success demonstrates remarkable efficacy at just 24 weeks of treatment.
While the trial didn't achieve statistical significance on fibrosis improvement without MASH worsening (34.5% vs 25.9% placebo), the supplemental AI-based analysis presents compelling evidence of anti-fibrotic activity, with 30.6% of participants on 1.8 mg achieving ≥60% fibrosis reduction versus just 8.2% on placebo (p<0.001). The statistically significant improvements in non-invasive fibrosis markers (ELF score, VCTE) further support this anti-fibrotic potential.
What truly distinguishes pemvidutide is its 6.2% weight loss at 24 weeks with continuing trajectory and exceptional tolerability profile - treatment discontinuations due to adverse events were remarkably low at 0-1.2% versus 2.4% for placebo. No serious adverse events related to treatment were reported, addressing a critical concern with MASH therapeutics.
The 62.8% reduction in liver fat content and 34.4 IU/L decrease in ALT levels demonstrate powerful metabolic effects beyond histological improvements. The combination of efficacy across multiple endpoints with minimal side effects positions pemvidutide as potentially best-in-class among MASH treatments currently in development.
The strong results likely support Altimmune's planned FDA End of Phase 2 meeting, potentially accelerating advancement to pivotal Phase 3 trials. With MASH affecting millions and projected to grow dramatically, pemvidutide represents a significant commercial opportunity addressing a critical unmet medical need.
First product candidate to demonstrate significant MASH effects and weight loss at 24 weeks
Trial met its primary endpoint with statistically significant MASH resolution without worsening of fibrosis in up to
Fibrosis improvement without worsening of MASH in up to
Supplemental AI-based analysis demonstrated statistically significant reductions in liver fibrosis at 24 weeks
Weight loss of up to
Potentially best-in-class tolerability, with less than
Conference call to be held on June 26, 2025 at 8:30 am ET
GAITHERSBURG, Md., June 26, 2025 (GLOBE NEWSWIRE) -- Altimmune, Inc. (Nasdaq: ALT), a late clinical-stage biopharmaceutical company developing novel peptide-based therapeutics for liver and cardiometabolic diseases, today announced positive topline results from the IMPACT Phase 2b trial of pemvidutide in metabolic dysfunction-associated steatohepatitis (MASH).
The Phase 2b trial enrolled 212 participants with biopsy-confirmed MASH and fibrosis stages F2/F3 with and without diabetes randomized 1:2:2 to receive either weekly subcutaneous pemvidutide at 1.2 mg or 1.8 mg doses or placebo for 24 weeks. Treatment discontinuation rates were low, with only
“These data represent an important step forward in the development of pemvidutide for the treatment of MASH and reinforce our conviction in its potential to disrupt the treatment paradigm in this serious and rapidly growing disease,” said Vipin K. Garg, Ph.D., President and Chief Executive Officer of Altimmune. “Despite a prevalence expected to exceed 27 million by 2030 in the United States alone, current treatment options are limited. We are excited to continue our efforts to bring this potentially transformative therapy to MASH patients.”
Dr. Mazen Noureddin, Professor of Medicine at the Houston Methodist Hospital and Co-Chairman of the Board for Summit and Pinnacle Clinical Research, commented, “The combination of MASH resolution and weight loss achieved at only 24 weeks is unique among drugs in development for MASH. The tolerability of pemvidutide was also impressive, with one of the lowest rates of AE-related drug discontinuations observed in any MASH clinical trial to date. The significant reduction in fibrosis in AI-based readings and its corroboration with established NITs suggest that pemvidutide has potent anti-fibrotic activity and that statistical significance on the fibrosis improvement endpoint could be achieved with longer durations of treatment.”
Dr. Scott Harris, Chief Medical Officer of Altimmune, emphasized that “Based on the results generated in the IMPACT trial, pemvidutide demonstrated significant MASH resolution and encouraging evidence of fibrosis improvement at 24 weeks. Additionally, when one considers the weight loss and favorable tolerability associated with pemvidutide, we believe that there is a clear path to a successful End of Phase 2 meeting with the FDA in the fourth quarter of 2025, enabling rapid progression to Phase 3.”
Highlights from the 24-week Topline Results
- In an ITT analysis, MASH resolution without worsening of fibrosis was achieved in
59.1% and52.1% of participants treated with pemvidutide 1.2 mg and 1.8 mg, respectively, vs.19.1% of participants treated with placebo (p< 0.0001, both doses). - In an additional ITT analysis, fibrosis improvement without worsening of MASH was achieved in
31.8% and34.5% of participants treated with pemvidutide 1.2 mg and 1.8 mg vs.25.9% of participants treated with placebo (differences not significant). - A supplemental AI-based analysis demonstrated statistically significant reductions in fibrosis, which included
30.6% of participants receiving pemvidutide 1.8 mg achieving a60% or more reduction in fibrosis compared to8.2% receiving placebo (p< 0.001). - Pemvidutide-treated participants also achieved statistically significant reductions in non-invasive tests of fibrosis (ELF and VCTE) and inflammation (alanine aminotransferase, ALT).
- A total of
25.8% and24.1% of participants receiving pemvidutide 1.2 mg and 1.8 mg, respectively, achieved the stringent endpoint of MASH resolution and fibrosis improvement versus13.5% in participants receiving placebo (differences not significant). - Participants receiving pemvidutide 1.2 mg and 1.8 mg achieved weight loss of
5.0% and6.2% vs.1.0% in placebo (p< 0.001), with the trajectory showing no plateauing at 24 weeks. - Liver fat reductions of
58.0% and62.8% were achieved in participants who received pemvidutide 1.2 mg and 1.8 mg, respectively, vs.16.2% in participants who received placebo (p< 0.001, both doses). - AEs leading to treatment discontinuation were
0.0% and1.2% for pemvidutide 1.2 mg and 1.8 mg, respectively, vs.2.4% in participants on placebo. - No SAEs related to study drug or arrhythmias were reported at 24 weeks.
- Glycemic control was maintained with minimal changes in HbA1C regardless of diabetic status.
| Primary Endpoint (ITT analyses) | Placebo (N=85) | Pemvidutide 1.2 mg (N=42) | Pemvidutide 1.8 mg (N=85) |
| MASH resolution without worsening of fibrosis (%; LSM, Chi-Square Test) | 19.1 | 59.1**** | 52.1**** |
| Fibrosis improvement without worsening of MASH (%; LSM, Chi- Square Test) | 25.9 | 31.8 | 34.5 |
**** p< 0.0001 vs. placebo; LSM, least squares mean
| Secondary Endpoints | Placebo (N=85) | Pemvidutide 1.2 mg (N=42) | Pemvidutide 1.8 mg (N=85) |
| Proportion of participants achieving the composite of both MASH resolution and improvement of liver fibrosis at 24 weeks (%; LSM, Chi- Square Test) | 13.5 | 25.8 | 24.1 |
| Relative change in body weight at 24 weeks (%; LSM, MMRM) | -1.0 | -5.0*** | -6.2*** |
*** p< 0.001 vs. placebo; LSM, least square mean; MMRM, mixed model for repeated measures
| Other Secondary Endpoints | Placebo | Pemvidutide 1.2 mg | Pemvidutide 1.8 mg |
| Relative reduction in liver fat content by MRI-PDFF (%; LSM, ANCOVA) | 16.2 N=75 | 58.0*** N=40 | 62.8*** N=79 |
| Absolute change in alanine aminotransferase (ALT) (IU/L; LSM, MMRM) | -10.0 N=85 | -34.6*** N=42 | -34.4*** N=85 |
| Absolute change in Enhanced Liver Fibrosis (ELF) score (LSM, ANCOVA) | 0.03 N=73 | -0.6*** N=40 | -0.5*** N=76 |
| Absolute change in Vibration- Controlled Transient Elastography (VCTE) (kPa; LSM, ANCOVA) | -0.5 N=75 | -3.3** N=38 | -2.0* N=78 |
| Proportion of participants with reduction of > 0.5 ELF + CMH) | 5.9 N=85 | 38.1†††† N=42 | 20.0† N=85 |
* p< 0.05, ** p< 0.005, *** p< 0.001 vs. placebo (ANCOVA or MMRM)
† p< 0.05, †††† p< 0.0001 vs. placebo; LSM, least square mean; CMH, Cochran-Mantel-Haenszel; ANCOVA, analysis of co-variance
| AI-based Fibrosis Analysis (ITT analyses) | Placebo (N=85) | 1.2 mg (N=42) | 1.8 mg (N=85) |
| Proportion of participants with a reduction (%; CMH) | 21.2 | 38.1† | 49.4††† |
| Proportion of participants with a reduction (%; CMH) | 17.6 | 31.0 | 43.5††† |
| Proportion of participants with a reduction (%; CMH) | 12.9 | 19.0 | 35.3††† |
| Proportion of participants with a reduction (%; CMH) | 8.2 | 11.9 | 30.6††† |
† p< 0.05, ††† p< 0.001 vs. placebo; CMH, Cochran-Mantel-Haenszel
| Adverse Events (AEs) | Placebo (N=85) | 1.2 mg (N=42) | 1.8 mg (N=85) |
| Serious AEs, n (%) | 3 (3.5) | 1 (2.4) | 3 (3.5) |
| Serious AEs related to study med, n (%) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| Severe AEs, n (%) | 2 (2.4) | 1 (2.4) | 4 (4.7) |
| AEs leading to treatment discontinuation, n (%) | 2 (2.4) | 0 (0.0) | 1 (1.2) |
| AEs of Special Interest, n (%) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
Conference Call and Webcast
Altimmune will host a conference call and webcast on Thursday, June 26, 2025 at 8:30 am ET to review the Topline IMPACT data. In addition to remarks from Altimmune management, the call will include a discussion of the data and its implications with IMPACT Principal Investigator, Mazen Noureddin, M.D., MHSc.
The event will be available via the Events section of the Altimmune website.
About the IMPACT Study
The IMPACT (NCT05989711) trial enrolled 212 participants with biopsy-confirmed MASH and fibrosis stages F2/F3 with and without diabetes randomized 1:2:2 to receive either weekly subcutaneous pemvidutide at 1.2 mg and 1.8 mg doses or placebo for 24 weeks. Key efficacy endpoints were MASH resolution without worsening of fibrosis, or fibrosis improvement without worsening of MASH at 24 weeks. Secondary endpoints included weight loss and non-invasive tests of fibrosis. Participants will receive a total of 48 weeks of treatment, and a final readout is anticipated in the fourth quarter of 2025.
About Pemvidutide
Pemvidutide is a novel, investigational, peptide-based 1:1 GLP-1/glucagon dual receptor agonist in development for the treatment of MASH, obesity, Alcohol Use Disorder (AUD) and Alcohol-associated Liver Disease (ALD). Activation of the GLP-1 and glucagon receptors is believed to mimic the complementary effects of diet and exercise on weight loss, with GLP-1 suppressing appetite and glucagon increasing energy expenditure. Glucagon is also recognized as having direct effects on hepatic fat metabolism, which is believed to lead to rapid reductions in levels of liver fat and serum lipids. In clinical trials to date, once-weekly pemvidutide has demonstrated statistically significant MASH resolution and positive trends in liver fibrosis improvement, compelling weight loss with class-leading lean mass preservation, and robust reductions in liver fat content, triglycerides, LDL cholesterol and blood pressure. The U.S. FDA has granted Fast Track designation to pemvidutide for the treatment of MASH. Pemvidutide completed the MOMENTUM Phase 2 obesity trial in 2024 and is being studied in the ongoing IMPACT Phase 2b MASH trial. IND applications in AUD and ALD have received FDA clearance, with a Phase 2 trial in AUD underway and a Phase 2 trial in ALD scheduled to commence in the third quarter of 2025.
About Altimmune
Altimmune is a late clinical-stage biopharmaceutical company focused on developing novel peptide-based therapeutics for liver and cardiometabolic diseases. The Company’s lead program is pemvidutide, a GLP-1/glucagon dual receptor agonist for the treatment of MASH, obesity, AUD and ALD. For more information, please visit www.altimmune.com.
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Forward-Looking Statement
Any statements made in this press release related to the development or commercialization of product candidates and other business and financial matters, including without limitation, trial results and data, including the results of the IMPACT Phase 2b Trial and statements relating to fibrosis improvement and the achievement of statistical significance on the fibrosis improvement endpoint, the timing of key milestones for the Company’s clinical assets, future plans or expectations for pemvidutide for the treatment of MASH, and the prospects for receiving regulatory approval or commercializing or selling any product or drug candidates, are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. In addition, when or if used in this press release, the words "may," "could," "should," "anticipate," "believe," "estimate," "expect," "intend," "plan," "predict" and similar expressions and their variants, as they relate to Altimmune, Inc. may identify forward-looking statements. The Company cautions that these forward-looking statements are subject to numerous assumptions, risks, and uncertainties, which change over time. Important factors that may cause actual results to differ materially from the results discussed in the forward looking statements or historical experience include risks and uncertainties, including risks relating to: delays in regulatory review, manufacturing and supply chain interruptions, access to clinical sites, enrollment, adverse effects on healthcare systems and disruption of the global economy; the reliability of the results of studies relating to human safety and possible adverse effects resulting from the administration of the Company's product candidates; the Company's ability to manufacture clinical trial materials on the timelines anticipated; and the success of future product advancements, including the success of future clinical trials. Further information on the factors and risks that could affect the Company's business, financial conditions and results of operations are contained in the Company's filings with the U.S. Securities and Exchange Commission, including under the heading "Risk Factors" in the Company's most recent annual report on Form 10-K, quarterly report on Form 10-Q and the Company’s other filings with the SEC, which are available at www.sec.gov.
Company Contact:
Greg Weaver
Chief Financial Officer
Phone: 240-654-1450
ir@altimmune.com
Investor Contact:
Lee Roth
Burns McClellan
Phone: 646-382-3403
lroth@burnsmc.com
Media Contact:
Jake Robison
Inizio Evoke Comms
Phone: 619-849-5383
jake.robison@inizioevoke.com
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FAQ
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