Wave Life Sciences Announces Submission of First Clinical Trial Application for WVE-007 (siRNA Targeting INHBE) in Obesity
Wave Life Sciences (WVE) has submitted its first clinical trial application for WVE-007, a novel obesity treatment using siRNA technology to silence the INHBE gene. The therapy aims to achieve sustainable weight loss through fat burning while maintaining muscle mass, with potential for once or twice-annual dosing. Clinical trials are expected to begin in Q1 2025.
Preclinical studies in mice showed that a single dose of WVE-007 achieved weight loss comparable to semaglutide, and when used in combination, doubled the weight loss effect. The upcoming Phase 1 trial will evaluate safety, tolerability, pharmacokinetics, and biomarkers in adults with overweight or obesity.
Wave Life Sciences (WVE) ha presentato la sua prima domanda di sperimentazione clinica per WVE-007, un innovativo trattamento per l'obesità che utilizza la tecnologia siRNA per silenziare il gene INHBE. La terapia mira a ottenere una perdita di peso sostenibile attraverso il bruciare i grassi, mantenendo al contempo la massa muscolare, con la possibilità di dosaggi una o due volte all'anno. Le sperimentazioni cliniche dovrebbero iniziare nel primo trimestre del 2025.
Studi preclinici su topi hanno mostrato che una singola dose di WVE-007 ha raggiunto una perdita di peso comparabile a quella del semaglutide e, se usato in combinazione, ha raddoppiato l'effetto di perdita di peso. La prossima sperimentazione di Fase 1 valuterà la sicurezza, la tollerabilità, la farmacocinetica e i biomarcatori negli adulti in sovrappeso o obesi.
Wave Life Sciences (WVE) ha presentado su primera solicitud de ensayo clínico para WVE-007, un novedoso tratamiento para la obesidad que utiliza tecnología de siRNA para silenciar el gen INHBE. La terapia tiene como objetivo lograr una pérdida de peso sostenible a través de la quema de grasa, manteniendo al mismo tiempo la masa muscular, con potencial para dosificaciones una o dos veces al año. Se espera que los ensayos clínicos comiencen en el primer trimestre de 2025.
Los estudios preclínicos en ratones mostraron que una sola dosis de WVE-007 logró una pérdida de peso comparable a la del semaglutide y, cuando se utilizó en combinación, duplicó el efecto de pérdida de peso. El próximo ensayo de Fase 1 evaluará la seguridad, la tolerabilidad, la farmacocinética y los biomarcadores en adultos con sobrepeso u obesidad.
웨이브 라이프 사이언스(WVE)는 INHBE 유전자를 침묵시키기 위해 siRNA 기술을 사용하는 새로운 비만 치료제 WVE-007에 대한 첫 임상 시험 신청서를 제출했습니다. 이 요법은 근육량을 유지하면서 지방 연소를 통해 지속 가능한 체중 감소를 달성하는 것을 목표로 하며, 연 1~2회의 투여 가능성이 있습니다. 임상 시험은 2025년 1분기 시작될 것으로 예상됩니다.
마우스에 대한 전임상 연구에서 WVE-007의 단일 투여가 세마글루타이드와 유사한 체중 감소를 달성했으며, 함께 사용할 경우 체중 감소 효과를 두 배로 증가시켰습니다. 예정된 1상 시험은 비만 또는 과체중 성인에서 안전성, 내약성, 약물 동태 및 바이오마커를 평가할 것입니다.
Wave Life Sciences (WVE) a soumis sa première demande d'essai clinique pour WVE-007, un nouveau traitement de l'obésité utilisant la technologie siRNA pour silencer le gène INHBE. Cette thérapie vise à obtenir une perte de poids durable par la combustion des graisses tout en maintenant la masse musculaire, avec un potentiel pour une ou deux administrations par an. Les essais cliniques devraient commencer au premier trimestre 2025.
Des études précliniques sur des souris ont montré qu'une seule dose de WVE-007 a entraîné une perte de poids comparable à celle du sémaglutide, et lorsqu'elle est utilisée en combinaison, elle double l'effet de perte de poids. Le prochain essai de phase 1 évaluera la sécurité, la tolérance, la pharmacocinétique et les biomarqueurs chez des adultes en surcharge pondérale ou obèses.
Wave Life Sciences (WVE) hat seinen ersten Antrag auf klinische Erprobung für WVE-007 eingereicht, eine neuartige Behandlung von Adipositas, die die siRNA-Technologie zur Stilllegung des INHBE-Gens nutzt. Die Therapie zielt darauf ab, nachhaltigen Gewichtsverlust durch Fettverbrennung bei gleichzeitiger Erhaltung der Muskelmasse zu erreichen, mit dem Potenzial für einmal oder zweimal jährliche Dosen. Die klinischen Studien sollen im ersten Quartal 2025 beginnen.
Präklinische Studien an Mäusen zeigten, dass eine einzelne Dosis von WVE-007 einen Gewichtsverlust erzielte, der mit dem von Semaglutid vergleichbar ist, und bei gleichzeitiger Anwendung die Wirkung des Gewichtsverlusts verdoppelte. Die bevorstehende Phase-1-Studie wird die Sicherheit, Verträglichkeit, Pharmakokinetik und Biomarker bei übergewichtigen oder fettleibigen Erwachsenen bewerten.
- Preclinical results showed weight loss comparable to semaglutide
- Single dose doubled weight loss when combined with semaglutide
- Potential for once or twice-annual administration frequency
- Demonstrated ability to prevent weight regain after semaglutide discontinuation
- Novel mechanism targeting INHBE supported by human genetic evidence
- Clinical trials not yet started
- Efficacy in humans remains unproven
- Market entry timeline uncertain pending clinical trial results
Insights
Wave Life Sciences' CTA submission for WVE-007 represents a potentially transformative approach in the $100+ billion obesity market. The siRNA therapeutic targeting INHBE showcases distinct competitive advantages: once or twice-yearly dosing versus weekly/monthly for GLP-1s, preservation of muscle mass and potential synergistic effects with existing treatments like semaglutide.
The preclinical data is particularly compelling - achieving weight loss comparable to semaglutide in DIO mouse models while doubling efficacy when used in combination. The prevention of weight regain post-semaglutide discontinuation addresses a critical unmet need. The genetic validation through human loss-of-function mutations provides strong mechanistic support for the target.
The upcoming Phase 1 trial in 1Q 2025 could be a significant catalyst. Given the novel mechanism and potential positioning across the obesity treatment spectrum, successful early clinical validation could drive substantial value creation.
The obesity therapeutics landscape is experiencing unprecedented growth, driven by GLP-1 drugs like Wegovy and Zepbound. WVE-007's differentiated approach through INHBE targeting could capture significant market share by addressing key limitations of current treatments - notably frequent dosing requirements and muscle loss concerns.
The dual positioning strategy - both as monotherapy and combination treatment with GLP-1s - expands the potential market opportunity. The ability to prevent weight regain after GLP-1 discontinuation could establish WVE-007 as an essential maintenance therapy. Based on current obesity drug pricing and market dynamics, successful commercialization could translate to multi-billion dollar peak sales potential.
The scientific rationale behind WVE-007 is robust, leveraging human genetic evidence and Wave's proprietary GalNAc-siRNA platform. The focus on INHBE silencing represents an innovative approach to metabolic regulation through enhanced lipolysis while preserving muscle mass - a critical differentiator from existing therapies.
The planned Phase 1 trial's comprehensive endpoints, including biomarkers for target engagement and body composition analysis, should provide early insights into WVE-007's therapeutic potential. The preclinical efficacy data, particularly the synergistic effects with semaglutide and prevention of weight regain, suggests potential for a paradigm shift in obesity treatment algorithms.
WVE-007 is a novel approach for treating obesity and is designed to silence INHBE to achieve healthy, sustainable weight loss through fat burning, muscle maintenance and the potential for once or twice-annual administration
WVE-007 is Wave’s first siRNA program to enter clinical development and uses best-in-class oligonucleotide chemistry and GalNAc delivery
Wave expects to initiate the first-in-human study of WVE-007 in 1Q 2025
CAMBRIDGE, Mass., Dec. 23, 2024 (GLOBE NEWSWIRE) -- Wave Life Sciences Ltd. (Nasdaq: WVE), a clinical-stage biotechnology company focused on unlocking the broad potential of RNA medicines to transform human health, today announced the submission of its first clinical trial application (CTA) for WVE-007 in obesity. WVE-007 is an investigational GalNAc-conjugated small interfering RNA (siRNA) designed to silence Inhibin βE (INHBE) gene expression, which would induce fat burning (lipolysis) to decrease body weight without impacting muscle mass. Wave expects CTA approval and initiation of the first-in-human study of WVE-007 in the first quarter of 2025.
“Our WVE-007 program, which uses Wave’s best-in-class GalNAc-siRNA capabilities with proprietary chemistry, has potential to be dosed once or twice annually and may ultimately be used across the obesity treatment continuum for sustainable weight loss and cardiometabolic risk reduction,” said Paul Bolno, MD, MBA, President and Chief Executive Officer at Wave Life Sciences. “With a growing understanding of human genetics and opportunities to directly impact adipose tissue, INHBE has emerged as an exciting, novel therapeutic target to address obesity, without the challenges of current standard-of-care therapeutics.”
Human genetics provide strong evidence for INHBE as a therapeutic target. Individuals who have a protective loss-of-function mutation in the INHBE gene have a healthier cardiometabolic profile, including less abdominal fat, lower triglycerides, and lower risk of type 2 diabetes and cardiovascular disease. WVE-007 is designed to induce this healthy phenotype through INHBE gene silencing, leading to fat burning and improvements in metabolic health. In preclinical studies using a mouse model of diet induced obesity (DIO), a single dose of Wave’s INHBE siRNA led to weight loss on par with semaglutide, with no muscle loss. When administered as an add-on to semaglutide, a single dose doubled the amount of weight loss. In another study, Wave’s INHBE siRNA also prevented weight regain when semaglutide treatment was discontinued.
Wave’s first-in-human study of WVE-007 is a Phase 1 clinical trial in adults living with overweight or obesity. The trial is designed to assess safety, tolerability, pharmacokinetics, and biomarkers for target engagement, as well as body composition and metabolic health.
About Wave Life Sciences
Wave Life Sciences (Nasdaq: WVE) is a biotechnology company focused on unlocking the broad potential of RNA medicines to transform human health. Wave’s RNA medicines platform, PRISM®, combines multiple modalities, chemistry innovation and deep insights in human genetics to deliver scientific breakthroughs that treat both rare and prevalent disorders. Its toolkit of RNA-targeting modalities includes editing, splicing, RNA interference and antisense silencing, providing Wave with unmatched capabilities for designing and sustainably delivering candidates that optimally address disease biology. Wave’s diversified pipeline includes clinical programs in Duchenne muscular dystrophy, Alpha-1 antitrypsin deficiency and Huntington’s disease, as well as a preclinical program in obesity. Driven by the calling to “Reimagine Possible”, Wave is leading the charge toward a world in which human potential is no longer hindered by the burden of disease. Wave is headquartered in Cambridge, MA. For more information on Wave’s science, pipeline and people, please visit www.wavelifesciences.com and follow Wave on X (formerly Twitter) and LinkedIn.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, our expectations for WVE-007, our investigational GalNAc-conjugated small interfering RNA (siRNA) designed to silence Inhibin βE (INHBE) gene expression and the anticipated therapeutic benefits thereof, including the potential of WVE-007 to treat obesity; the anticipated timing to initiate the first-in-human clinical program with WVE-007; the novelty of our approach to silence INHBE in order to achieve healthy, sustainable weight loss through fat burning, muscle maintenance and the potential for once or twice-annual dosing; and the potential benefits of WVE-007 compared with other investigational obesity treatments and current standard-of-care obesity therapeutics. The words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release and actual results may differ materially from those indicated by these forward-looking statements as a result of these risks, uncertainties and important factors, including, without limitation, the risks and uncertainties described in the section entitled “Risk Factors” in Wave’s most recent Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC), as amended, and in other filings Wave makes with the SEC from time to time. Wave undertakes no obligation to update the information contained in this press release to reflect subsequently occurring events or circumstances.
Investor Contact:
Kate Rausch
+1 617-949-4827
krausch@wavelifesci.com
Media Contact:
Alicia Suter
+1 617-949-4817
asuter@wavelifesci.com
FAQ
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