WVE-N531 / Wave Life Sciences - LARVOL DELTA

Wave also announced today that the company met with the U.S. Food and Drug Administration (FDA) on WVE-N531 to discuss its interim 24-week data and initial plans for the confirmatory trial…. (GlobeNewswire) - "Based on the FDA feedback and the 48-week data, Wave intends to file a New Drug Application (NDA) in 2026 for accelerated approval of WVE-N531. The NDA filing will be based on all FORWARD-53 data, which will include additional data to support monthly dosing.....Wave expects to submit multiple clinical trial applications (CTAs) for other exon skipping programs in 2026."

FDA filing • New trial • Duchenne Muscular Dystrophy

Wave Life Sciences Announces Positive Data from FORWARD-53 Clinical Trial in DMD Including Significant Functional Benefit and Reversal of Muscle Damage after 48 Weeks of Dosing with WVE-N531 (GlobeNewswire) - P1/2 | N=11 | FORWARD-53 (NCT04906460) | Sponsor: Wave Life Sciences Ltd. | "The analysis was conducted after 48 weeks of treatment with 10 mg/kg WVE-N531 dosed every two weeks (Q2W)....Additionally, the data demonstrate substantial decreases in inflammation and necrosis, a statistically significant reversal of muscle fibrosis (28.6% reduction between week 24 to 48; p<0.01), and a transition from regeneration to maturation of muscle. A 50% decline (<0.001) in creatine kinase (CK), as well as decreases in IL-6 and MCP-1, were also observed....Dystrophin and exon skipping: Dystrophin expression stabilized between 24 and 48 weeks of dosing with a mean of 7.8% [95% CI: 5.4-10.3%; 24-week dystrophin was 9.0% (95% CI: 6.5-11.5%) and 48-week dystrophin was 6.4% (95% CI: 3.8-9.0%)...88% of boys (7/8) achieved greater than 5% average dystrophin between 24 and 48 weeks."

P1/2 data • Duchenne Muscular Dystrophy

Exon Skipping Programs (GlobeNewswire) - "FORWARD-53 is an ongoing Phase 2 open-label trial of WVE-N531. Muscle biopsies are taken after 24 and 48 weeks of dosing....Wave expects to deliver the 48-week FORWARD-53 data and feedback from regulators on a pathway to accelerated approval in 1Q 2025."

P2 data • Duchenne Muscular Dystrophy

Open-label Study of WVE-N531 in Patients with Duchenne Muscular Dystrophy (FORWARD-53) (clinicaltrials.gov) - P1/2 | N=11 | Active, not recruiting | Sponsor: Wave Life Sciences Ltd. | Trial completion date: May 2025 ➔ Oct 2026

Trial completion date • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Wave Life Sciences Receives FDA Rare Pediatric Disease Designation for WVE-N531 for the Treatment of Duchenne Muscular Dystrophy (GlobeNewswire) - "Wave Life Sciences Ltd...announced that the U.S. Food and Drug Administration (FDA) has granted Rare Pediatric Disease Designation to WVE-N531 for the treatment of boys with Duchenne muscular dystrophy (DMD) who are amenable to exon 53 skipping. WVE-N531 is currently being evaluated in the potentially registrational FORWARD-53 clinical trial and Wave expects to deliver data, including dystrophin protein expression from muscle biopsies after 24 weeks of treatment, in the third quarter of 2024."

FDA event • P1/2 data • Duchenne Muscular Dystrophy • Genetic Disorders

Evaluating Investigational PN-Containing Oligonucleotide WVE-N531 for Patients with Duchenne Muscular Dystrophy Amenable to Exon 53 Skipping: A Phase 1b/2 Open-Label Study (New Directions 2024) - No abstract available

Clinical • P1/2 data • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Open-label Study of WVE-N531 in Patients With Duchenne Muscular Dystrophy (FORWARD-53) (clinicaltrials.gov) - P1/2 | N=11 | Active, not recruiting | Sponsor: Wave Life Sciences Ltd. | Recruiting ➔ Active, not recruiting | Phase classification: P1b/2a ➔ P1/2 | Trial completion date: Dec 2022 ➔ May 2025 | Trial primary completion date: Dec 2022 ➔ Jan 2025

Enrollment closed • Phase classification • Trial completion date • Trial primary completion date • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

WVE-N531 with PN backbone modification significantly enhances drug concentrations in heart, diaphragm, and skeletal muscles in non-human primates (MDA 2024) - "WVE-N531 achieved high mean concentrations in skeletal muscle in NHPs, with even higher general exposure observed in the heart and diaphragm. Together, these data illustrate WVE-N531’s excellent tissue uptake and distribution in both skeletal and non-skeletal muscles."

Cardiomyopathy • Cardiovascular • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Atrophy • Muscular Dystrophy • Respiratory Diseases

PN-containing oligonucleotides yield high levels of exon skipping and dystrophin protein restoration in preclinical models for DMD (MDA 2024) - "Notably, a PN-containing oligonucleotide called WVE-N531 is being developed for patients with DMD amenable to exon 53 skipping. In a Phase 1b/2 trial, three boys were administered three biweekly doses of WVE-N531, which resulted in substantial accumulation and exon-skipping in skeletal muscle."

Preclinical • CNS Disorders • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy • MYOD1 • YOD1

First clinical evidence for satellite cell targeting in DMD: Results from Part A of a Phase 1b/2 study of WVE-N531 (MDA 2024) - P1b/2a | "This finding represents the first clinical evidence of a potential therapeutic for DMD having the ability to access satellite cells. Further studies are necessary to assess the therapeutic potential of WVE-N531 and the impact of exon-skipping in satellite cells in patients with DMD."

Clinical • P1/2 data • CNS Disorders • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy • PAX7

A phase 1b/2 open-label study of WVE-N531 in patients with Duchenne muscular dystrophy: part B study design and rationale (WMS 2023) - No abstract available

Clinical • P1/2 data • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

WVE-N531 yields 53% mean exon 53 skipping in skeletal muscle of boys with Duchenne muscular dystrophy (DMD) after three biweekly doses (WMS 2023) - No abstract available

Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

WVE-N531 with PN backbone modification significantly enhances drug concentrations in heart, diaphragm, and skeletal muscles in non-human primates (WMS 2023) - No abstract available

Wave Life Sciences to Highlight Leading RNA Editing Capability and Multimodal Discovery and Development Platform at ASGCT 26th Annual Meeting (GlobeNewswire) - "Best-in-class exon skipping clinical data for WVE-N531 in Duchenne muscular dystrophy (DMD) also highlighted in oral presentation."

P1/2 data • Duchenne Muscular Dystrophy • Muscular Dystrophy

Phosphoryl Guanidine-Containing Oligonucleotides Support Exon Skipping in Skeletal Muscle in Mice and Boys with DMD (ASGCT 2023) - P1b/2a | "Preliminary clinical data provide evidence that WVE-N531, which is the first exon-skipping oligonucleotide containing PN chemistry to be tested in the clinic, is leading to substantial exon skipping after three biweekly doses. These data suggest PN chemistry may be impacting pharmacology at the level of human muscle tissue. Although measured dystrophin in patients was low, it is expected that dystrophin production would lag RNA splicing."

Preclinical • Infectious Disease • Muscular Atrophy • Muscular Dystrophy • Novel Coronavirus Disease

Recent Trends in Antisense Therapies for Duchenne Muscular Dystrophy. (PubMed, Pharmaceutics) - "These upcoming therapies often utilize novel drug chemistries to address limitations of existing therapies, and their development could herald the next generation of antisense therapy. This review article aims to summarize the current state of development for antisense-based therapies for the treatment of Duchenne muscular dystrophy, exploring candidates designed for both exon skipping and gene knockdown."

Journal • Review • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Phosphoryl guanidine-containing backbone modifications enhance exon skipping, dystrophin restoration and survival in a severe mouse model for DMD (WMS 2022) - P1b/2a | "These data demonstrate that chemical optimization can profoundly impact oligonucleotide pharmacology and highlight the therapeutic potential of stereopure PN-containing SSOs in DMD. Further, these data help to support the advancement of WVE-N531, an investigational compound currently in clinical testing (NCT04906460) that incorporates this technology, for the treatment of patients with DMD amenable to exon 53 skipping."

Preclinical • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Open-label Study of WVE-N531 in Patients With Duchenne Muscular Dystrophy (clinicaltrials.gov) - P1b/2a | N=15 | Recruiting | Sponsor: Wave Life Sciences Ltd. | Trial completion date: Sep 2022 ➔ Dec 2022 | Trial primary completion date: Sep 2022 ➔ Dec 2022

Trial completion date • Trial primary completion date • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Open-label Study of WVE-N531 in Patients With Duchenne Muscular Dystrophy (clinicaltrials.gov) - P1b/2a; N=15; Recruiting; Sponsor: Wave Life Sciences Ltd.; Not yet recruiting ➔ Recruiting; Initiation date: Jun 2021 ➔ Sep 2021

Clinical • Enrollment open • Trial initiation date • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy • MRI

Wave Life Sciences Highlights Pipeline Progress and Expansion Leveraging New PN Backbone Chemistry Modifications (GlobeNewswire) - "Advancing three clinical programs utilizing compounds containing Wave’s novel PN backbone chemistry modifications to first-in-human studies: Wave expects to initiate dosing in three proof-of-concept studies in 2021, which will assess target engagement, impact on key disease biomarkers, and initial safety for...WVE-N531 in Duchenne muscular dystrophy (DMD)."

New trial • CNS Disorders • Duchenne Muscular Dystrophy

Wave Life Sciences Reports Third Quarter 2020 Financial Results and Provides Business Update (GlobeNewswire) - "Exon 53 program (WVE-N531) for Duchenne muscular dystrophy (DMD): Based on compelling in vitro and in vivo preclinical results from compounds incorporating Wave’s novel PN chemistry, Wave is advancing WVE-N531 to explore splicing in dystrophic muscle. Planning is underway for a clinical trial to assess dystrophin production and initial safety in patients with DMD amenable to exon 53 skipping...Wave expects to submit a CTA for WVE-N531 in the first quarter of 2021."

New trial • Preclinical • Duchenne Muscular Dystrophy