Investigational Drug and Improvements
The investigational drug zeleciment basivarsen (z-basivarsen) has shown potential for functional improvement in patients with myotonic dystrophy type 1 (DM1), as suggested by data from the phase I/II ACHIEVE trial.
This analysis sought to determine whether a larger group of patients experienced similar efficacy trends observed in a smaller cohort of six participants who received the registrational dose of 6.8 mg/kg once every eight weeks. It included a pooled-dose group of 26 DM1 patients assessed over a 12-month period during the multiple ascending dose portion of the ACHIEVE trial.
After one year, participants demonstrated sustained improvement from baseline in hand myotonia, with assessment through video hand-opening time (vHOT), as reported by Dr. Shauna Andersson, vice president of clinical development at Dyne Therapeutics, during the recent meeting of the American Association of Neuromuscular and Electrodiagnostic Medicine.
The pooled-dose group recorded a mean baseline vHOT of 8.2 seconds, which reduced by 3.2 seconds at the six-month mark. This represented a 3.6 second improvement compared to the placebo group, which only increased its vHOT by 0.4 seconds at the same time point.
Participants in the pooled-dose group also experienced sustained functional improvements as assessed by the 5 times sit-to-stand (5xSTS) test and displayed enhanced strength through quantitative muscle testing (QMT) total scores. Additionally, they reported a reduction in disease burden.
When compared to a natural history cohort, z-basivarsen-treated participants exhibited superior functional and strength outcomes as well as improvements in patient-reported Myotonic Dystrophy Health Index scores.
Dr. Andersson further noted that z-basivarsen maintained a favorable safety profile, with treatment-related adverse events including infusion-related reactions, nasopharyngitis, diarrhea, headache, procedural pain, influenza, and back pain. Importantly, no serious treatment-emergent adverse events linked to the study drug were reported.
“These data address two important questions,” Dr. Andersson emphasized. “Firstly, despite the majority of participants in this larger group receiving lower doses than our chosen registrational dose, we still observed the same improvement pattern from baseline at 12 months that we previously noticed in the smaller cohort treated at the full registrational dose.”
“Secondly, when comparing this larger group to a well-matched cohort of untreated DM1 patients, we observed a clear divergence at 12 months from the natural course of the disease, across every reported endpoint,” she stated. “Collectively, these findings reinforce our confidence in z-basivarsen’s potential for delivering functional improvement to individuals living with myotonic dystrophy type 1.”
Myotonic dystrophy type 1 is a rare progressive disorder caused by mutations in the DMPK gene, leading to widespread RNA splicing disruptions. Symptoms for adult-onset DM1 typically emerge between ages 20 and 40, and there are currently no disease-modifying therapies available, with treatment options mainly focused on symptom management.
Z-basivarsen (DYNE-101) is an investigational drug that comprises an antisense oligonucleotide conjugated to an antigen-binding fragment targeting the transferrin receptor 1. The drug aims to reduce toxic nuclear DMPK RNA to free splicing proteins, thereby facilitating normal mRNA processing.
This treatment is being explored in the phase I/II ACHIEVE trial as well as the phase III HARMONIA trial, which is currently recruiting participants. The primary endpoint of HARMONIA will assess the change from baseline in 5xSTS at 12 months.
Additionally, ACHIEVE includes a registrational expansion cohort (REC) to support potential regulatory submissions, including accelerated approval in the U.S. The primary endpoint for this cohort focuses on changes from baseline in middle finger myotonia measured by vHOT at 6 months compared to placebo.
The mean baseline vHOT value for the 71 participants enrolled in the ACHIEVE REC study is 8.3 seconds, with topline data anticipated from this cohort in the first quarter of 2027.
Disclaimer: This information is intended for educational purposes only and should not be considered as medical advice. Always consult a healthcare professional for medical guidance and treatment options.
Fuente: https://www.medpagetoday.com/meetingcoverage/aanem/123265
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