Recapping Research From 2023 MDA Clinical and Scientific Conference


As a recap from MDA 2023, get caught up on some of the latest news in neuromuscular diseases 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 diseases (NMD), including those with amyotrophic lateral sclerosis (ALS), myasthenia gravis (MG) and other neuromuscular conditions.

To recap the 2023 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, March 19-22, in Dallas, Texas, the team has culminated some of the biggest pieces of news to offer updates on new developments in literature about NMDs to spread awareness on the prevention and treatment of the conditions.

Click here for more coverage of MDA 2023.

Latest Literature

Losmapimod Demonstrates Significant Slowing of Facioscapulohumeral Muscular Dystrophy Over Long-Term Period

New long-term findings from the phase 2b ReDUX4 trial (NCT04003974) showed that treatment with losmapimod (Fulcrum Therapeutics) slowed disease progression and demonstrated maintenance of effect through a 96-week period in patients with facioscapulohumeral muscular dystrophy (FSHD), expanding on the previously reported 48-week results.1

Led by Leo H. Wang, MD, PhD, associate professor of neurology, University of Washington Medical Center, the study featured 80 adults, aged 18 to 65 years with genetically confirmed FSHD1 who were randomly assigned 1:1 to 15 mg losmapimod or placebo. Of these, 76 (99%) entered the open-label extension (OLE) after 48 weeks, and 74 (97%) were enrolled at week 96. All patients received study drug in the OLE, and had durability of treatment response assessed through upper extremity function with Reachable Workspace (RWS).

The durability of treatment response in RWS was observed at 96 weeks in those on continuous losmapimod throughout the study. Patients on placebo who converted to study drug at week 48 also demonstrated trends of slowing or stopping disease progression. Of note, those who converted to losmapimod during the OLE had been exposed for an average of 47 to 72 weeks, depending on when they entered the OLE due to implementation of a COVID-19 protocol amendment.

Myasthenia Agent Zilucoplan Continues to Show Positive Efficacy in Long-Term Extension

Interim data from RAISE-XT, a phase 3, open-label extension (OLE) study of UCB Pharma’s zilucoplan, an agent currently under review for myasthenia gravis (MG), showed favorable long-term safety profile, with positive efficacy in those who continued treatment from the double-blind period and those who switched from placebo.2

RAISE-XT, an ongoing study, featured 199 patients with MG who participated in previously conduced phase 2 (NCT03315130) and phase 3 (NCT04115293) studies. Patients self-administered daily subcutaneous injections of 0.3 mg/kg zilucoplan and were assessed on the primary outcome of treatment-emergent adverse events (TEAEs). At data cutoff (February 18, 2022), participants had a median duration of exposure of 253 days (range, 29-1434) during RAISE-XT and the OLE portion of the phase 2 study for participants who continued in RAISE-XT.

At the 24-month period, 84.9% (n = 169) experienced a TEAE, and 23.1% (n = 46) documented serious AEs. Between both groups, the most common TEAEs were headache and worsening of MG, both occurring in 16.6% of patients. Throughout the study, 4 treatment-emergent deaths occurred, all in patients with multiple cardiovascular risk factors, and none of them were considered treatment related. Cardiac arrest was the cause in 2 patients, 1 patient experienced head injury, and 1 had severe pneumonia 2 days prior to death. Infections were reported in nearly half (49.2%) of the cohort, although most (86%) were non-serious.

Consensus Considerations Developed for SRP-9001 Adverse Event Management in DMD

A set of consensus considerations for the management of relevant adverse events (AEs) related to the use of the investigational gene therapy delandistrogene maxeparvovec (SRP-9001; Sarepta Therapeutics) in the treatment of Duchenne muscular dystrophy (DMD) has been established by the Delphi panel, which reviewed data from 3 clinical trials of the therapy.3

The considerations were for a set of occurring AEs: vomiting, myocarditis, acute liver injury, and immune-mediated myositis. The trials included in developing these considerations were Study 101 (NCT03375164; n = 4), Study 102 (NCT03769116; n = 41), and Study 103, also known as ENDEAVOR (NCT24626674; n = 40). The trials included a range of patients, including children as young as 3 years old and as old as 19 years, and both ambulatory and nonambulatory individuals with DMD.

For vomiting, the most commonly occurring AE (reported in 61.2% of patients), the Delphi panel noted those patients and caregivers should provide immediate follow-up if post-treatment vomiting occurs, while physicians should offer antiemetics as needed, with a recommended switch to intravenous steroids if oral administration is not able to be tolerated or retained.

Acute liver injury occurred in 36.5% of those in the utilized data, with most cases occurring within 4 to 8 weeks post infusion. The observed cases generally resolved within 2 months of onset. The Delphi panel offered considerations for patients and caregivers to provide immediate follow-up upon onset of symptoms such as jaundice or abdominal pain, and that close monitoring of liver function should be initiated, to be increased as clinically indicated.

Treg Suppressing Agent COYA 302 Shows Slowing of ALS Disease Progression

New data from a proof-of-concept study assessing Coya Therapeutics’ investigational agent COYA 302 showed that over a 48-week treatment period, patients with amyotrophic lateral sclerosis (ALS) showed amelioration in the progression of their disease.4 The therapeutic, designed to enhance proinflammatory T lymphocytes (Treg), successfully increased Treg suppressive function and was safe throughout the study.

In a cohort of 4 patients with ALS, the mean ALS Functional Rating Scale-Revised (ALSFRS-R) scores at week 24 (33.75 [±3.3]) and week 48 (32.00 [±7.8]) were not statistically different to those observed at baseline (33.5 [±5.9]). The study reported no discontinuations, no deaths or serious adverse events (AEs), with mild injection site reactions as the most common AE observed.

COYA 302 is a combination of 2 biologics with a dual mechanism of action, synergistically enhancing Treg function and depleting effector T cells, activated macrophages, and pro-inflammatory cytokines to further decrease inflammation. One of the many products in development by Coya, COYA 302 includes COYA 301 as part of its mechanism of action. This Treg-enhancing biologic therapy plays a key role in the development, expansion, activity, and survival of Tregs.

Post-Hoc Analysis of ADAPT Reveals Several Subgroup Responders to Efgartigimod

When grouping patients by clinical characteristics such as time from diagnosis, thymectomy status, and concomitant medications, new findings from the phase 3 ADAPT study (NCT03669588) showed that efgartigimod (Vyvgart; Argenx) is consistently effective across subgroups of individuals with generalized myasthenia gravis (gMG).5

The study featured 129 patients with acetylcholine receptor autoantibody positive (AChR-Ab+) gMG who received intravenous efgatigimod 10 mg/kg or placebo in cycles of 4 weekly infusions, with subsequent cycles based on clinical evaluation. In those who had less than 3 years since diagnosis, 76.8% (11 of 14) of efgartigimod-treated patients demonstrated at least a 2-point improvement for at least 4 consecutive weeks on Myasthenia Gravis Activities of Daily Living (MG-ADL) vs 23.5% of those on placebo (difference, 55.0%; 95% CI, 25.6-84.5). In the analysis, responder status was defined as at least 2-point improvement on MG-ADL or at least 3-point improvement on Quantitative Myasthenia Gravis (QMG) scores.

In non-thymectomized patients, 85.0% (17 of 20) on efgartigimod achieved responder status vs 32.4% (11 of 34) of those on placebo. An even greater between-group difference was seen for concomitant medications, as 84.6% (11 of 13) of those on efgartigimod while only receiving concomitant acetylcholinesterase inhibitors achieved responder status vs 16.7% of those on placebo (difference, 67.9%; 95% CI, 32.3-100.0). For those who received any corticosteroid, 63.0% (29 of 46) of patients on efgartigimod were responders compared with 29.4% (15 of 51) on placebo (difference, 33.6; 95% CI, 14.9-52.4). Results for other subgroups, along with the proportion of QMG responders, also favored efgartigimod.

1. Wang L, Han J, Shoskes J, Jiang J, Tawi R. Results from 96 weeks open-label extension of a phase 2 trial of losmapimod in subjects with FSHD: ReDUX4. Presented at: MDA 2023; March 19-22; Dallas, TX. Abstract 120.
2. Genge A, Hussain Y, Kaminski HJ, et al. Safety and tolerability of zilucoplan in RAISE-XT: a multicenter, open-label extension study in patients with myasthenia gravis. Presented at: MDA 2023; February 19-22; Dallas, TX. Abstract 145.
3. Goedecker N. Management of Select Adverse Events Following Delandistrogene Moxeparvovec Gene Therapy in Patients with DMD: Delphi Consensus Guidance. Presented at: MDA Clinical & Scientific Conference; March 19-22, 2023; Dallas, TX. Late-breaking session.
4. Coya Therapeutics announces positive results from a proof-of-concept academic clinical study for COYA 302 in amyotrophic lateral sclerosis (ALS). News release. Coya Therapeutics. March 21, 2023. Accessed March 23, 2023.
5. Ritt E, Bril V, Vu T, et al. Efgartigimod demonstrates consistent improvements in generalized myasthenia gravis across patient subgroups, including early in diagnosis. Presented at: MDA 2023; March 19-22; Dallas, TX. Abstract 134
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