Neuro News Roundup: World Duchenne Awareness Day


In honor of World Duchenne Awareness Day, held September 7, 2023, get caught up on some of the latest news in Duchenne muscular dystrophy as the NeurologyLive® team shares some of our data updates.

In recent months, the NeurologyLive® team has been covering the news and conducting interviews with experts on the latest updates in the clinical care of individuals with neuromuscular disorders, including those with Duchenne muscular dystrophy (DMD).

For World Duchenne Awareness Day — September 7, 2023 —the team has culminated some of the biggest pieces of news to offer updates on new developments in literature about DMD to spread awareness on the prevention and treatment of the condition.

Click here for more coverage of the latest neuromuscular news from NeurologyLive®.

Latest Literature

Duchenne Agent Pamrevlumab Fails to Meet Primary End Point in Phase 3 LELANTOS-2 Trial

In recent news, topline data from the phase 3 LELANTOS-2 trial (NCT04632940) showed that pamrevlumab (FibroGen) in combination with systemic corticosteroids failed to improve ambulatory function in ambulatory patients with Duchenne muscular dystrophy (DMD).1 FibroGen announced that they are in the process of assessing the totality of the data in order to decide the next steps and plan to communicate the full results of the study at an upcoming medical forum.

From baseline to week 52, the treatment did not meet the primary end point of change in North Star Ambulatory Assessment (NSAA) total score (placebo-corrected mean difference -0.528 points; 95% CI, -2.308 to 1.251; P = .5553). The secondary end points, change from baseline at week 52 in 4-stair climb velocity, 10-meter walk/run test, time to stand, time to loss of ambulation, and proportion of patients with greater than 10 seconds in the 10-meter walk/run test, were also not met.

LELANTOS-2 was a global, phase 3, randomized, double-blind trial that investigated pamrevlumab or placebo plus systemic corticosteroids. There were a total of 73 patients with ambulatory DMD, ranging between the ages of 6 and 12 years, enrolled in the study. The primary end point of the trial was ambulatory function measured by change in the NSAA total score from baseline to week 52. The participants enrolled were dosed with pamrevlumab (35 mg/kg IV on day 1 and every 2 weeks thereafter with last dose at week 52) or placebo.

Exon 44 Skipping Agent AOC 1044 Granted FDA Orphan Drug Designation for Duchenne Muscular Dystrophy

Recently, the FDA granted orphan drug designation to Avidity Biosciences’ AOC 1044, an investigational therapy in development for the treatment of Duchenne muscular dystrophy (DMD) in patients with mutations amenable to exon 44 skipping (DMD44).2 The therapy is being assessed in the phase 1/2 EXPLORE44 trial (NCT05670730) with results from the healthy volunteer portion of the trial expected to come in the fourth quarter of 2023.

AOC 1044, a proprietary monoclonal antibody, binds the transferrin receptor 1 conjugated with a phosphorodiamidate morpholino oligomers (PMOs) targeting exon 44. In a preclinical model using the therapy, a murine active AOC created durable exon skipping and functional dystrophin protein in skeletal muscle and heart tissue after a single intravenous dose. Earlier this year, the agent received FDA fast track designation for the treatment of DMD44, further validating its the potential in this patient population.2

EXPLORE44 is a randomized, placebo-controlled, double-blind, phase 1/2 trial evaluating AOC 1044 among healthy volunteers and patients with DMD44. The trial plans to assess the safety, tolerability, pharmacokinetics, and pharmacodynamic effects of single and multiple ascending doses of the therapy, administered intravenously. EXPLORE44, anticipated to have approximately 40 healthy volunteers and 24 patients with DMD44 enrolled between the ages of 7 and 27 years old, will primarily focus on exon skipping and dystrophin protein levels in treated patients, who will have the option to enroll into an extension study upon completion of the double-blind period.

FDA Clears NS-050/NCNP-03 for Phase 1/2 Trial of Duchenne Muscular Dystrophy

In recent news, the FDA cleared the start of a phase 1/2 study assessing NS-050/NCNP-03, NS Pharma’s investigational candidate for patients with Duchenne muscular dystrophy (DMD) amenable to exon 50 skipping therapy.3 Clinical trial enrollment for the trial in the United States is planned to start in the second half of 2023 and will be by NS Pharma's parent company, Nippon Shinyaku.

In the planned trial, patients with DMD will be assessed on dystrophin production, muscle strength, mobility, and functional exercise capacity. Once the trial is ready to begin the enrollment of participants, NS Pharma noted that additional information will then be provided. In addition to NS-050/NCNP-03, Nippon Shinyaku has 3 investigational exon skipping candidates in different stages of preclinical development for DMD.

In July 2023, the FDA granted Breakthrough Therapy Designation to NS-089/NCNP-02 (brogidirsen), another similar candidate for patients with DMD amenable to exon 44 skipping therapy.4 The decision was based on findings from a first-in-human, investigator-initiated clinical trial that was performed in Japan.5 Early that month, NS-089/NCNP-02 was granted Rare Pediatric Disease Designation by the FDA.4 The therapy, anantisense nucleotide developed between Nippon Shinyaku and the National Center for Psychiatry and Neurological Medicine, will be assessed in a phase 2 US-based study and a phase 2 Japan-based study.

Cure Rare Disease Identifies Toxicity Responsible for DMD Gene Therapy Death

According to a recent preprint of non-peer-reviewed research, investigations by Cure Rare Disease (CRD) have elucidated that a gene therapy prompted an innate immune signaling with capillary leak dose-limiting toxicity, leading to a patient death in a single patient trial (NCT05514249).6 The patient with Duchenne muscular dystrophy (DMD) was treated with a CRISPR-based adeno-associated virus vector (AAV9) gene therapy that delivered Cas9-VP64 transgene.

In November 2022, 27-year-old Terry Horgan, primary patient and the brother of CRD founder Rich Horgan, died 8 days following treatment of the gene therapy in the trial. The patient showed signs of mild cardiac dysfunction and pericardial effusion and then 6 days following the dosage, the patient acutely decompensated and sustained cardiac arrest. Two days later, the patient died.

The new post-mortem results from the patient showed severe acute-respiratory distress syndrome along with diffuse alveolar damage. Also, minimal expression of the transgene in the liver was observed when investigators assessed transgene expression. Overall, no evidence was observed of AAV9 antibodies or effector T cell reactivity in the patient.

Cell Therapy CAP-1002 Continues to Show Preservation of Cardiac Function in Open-Label Extension Study of DMD

Newly announced data from the open-label extension (OLE) period of the phase 2 HOPE-2 trial (NCT03406780) showed continued improvement of patients’ left ventricular ejection fraction (LVEF) after 2 years of treatment with CAP-1002 (Capricor), a cell therapy in development for Duchenne muscular dystrophy (DMD).7

Following the double-blind, placebo-controlled period, participants entered the OLE where they received CAP-1002 at 150 million cells per infusion every 3 months over the course of 24 months. In addition to showing improvement in LVEF, which was indicative of cardiac function, treated patients showed statistically significant benefits in Performance of the Upper Limb (PUL v2.0) scale after 2 years in comparison with the original rate of decline from the placebo group at 1 year.

LVEF, measured using cardiac MRI, was improved in 6 of the 9 patients at the end of the HOPE-2 study. Over time, there was an increasing correlation between PUL v2.0 and ejection fraction results (r = 0.75; P = .02). The therapy was well-tolerated with a safety profile that was consistent to previous observations.

1. FibroGen Announces Topline Results from LELANTOS-2, a Phase 3 Clinical Study of Pamrevlumab in Ambulatory Duchenne Muscular Dystrophy. News Release. FibroGen Inc. Published August 29, 2023. Accessed September 5, 2023.
2. Avidity Biosciences Receives FDA Orphan Drug Designation for AOC 1044 for Treatment of Duchenne Muscular Dystrophy in People with Mutations Amenable to Exon 44 Skipping. News Release. Avidity Biosciences. Published August 15, 2023. Accessed September 5, 2023.
3. NS Pharma Announces FDA Clearance to Initiate a Phase I/II Study for NS-050/NCNP-03, an Exon 50 Skipping Candidate for the Treatment of Duchenne Muscular Dystrophy. News Release. NS Pharma. Published June 15, 2023. Accessed September 5, 2023.
4. FDA Grants Breakthrough Therapy Designation to NS-089/NCNP-02 for the Treatment of Duchenne Muscular Dystrophy. News Release. NS Pharma. Published July 27, 2023. Accessed September 5, 2023.
5. Study shows the efficacy of antisense oligonucleotide-based exon 44 skipping drug, NS-089/NCNP-02, for patients with Duchenne muscular dystrophy (DMD) - Investigator-initiated Clinical Trial (First-in-human Trial) may lead to the world’s first effective drug for DMD amenable to exon 44 skipping. News Release. National Center of Neurology and Psychiatry. Published March 17, 2022. Accessed September 5, 2023.
6. Lek A, Wong B, Keeler AL, et al. Unexpected death of a Duchenne muscular dystrophy patient in an N-of-1 trial of rAAV9-delivered CRISPR-transactivator.medRxiv 2023. doi:10.1101/2023.05.16.23289881
7. Capricor Therapeutics announces positive 24-month results from ongoing HOPE-2 open label extension study of CAP-1002 in Duchenne muscular dystrophy. News release. June 30, 2023. Accessed September 5, 2023.
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