Data Roundup: March 2024 Features Updates in Muscular Dystrophies at MDA 2024

Last month, March 2024, the CGTLive® team was diligently tracking the latest data readouts and published literature on cell and gene therapies within oncology, ophthalmology, and rare diseases.

As more and more innovative therapies enter the clinical trial field, more data is accrued every month, buoying excitement in the field and sometimes making or breaking the fates of small biotech companies. Last month delivered promising data updates presented at the 2024 Muscular Dystrophy Association conference, for multiple therapies treating varied aspects and subtypes of muscular dystrophies. Our team has highlighted these and other updates below.

Click the read more buttons for more details and information about each update.

BlueRock Therapeutics' Parkinson Disease Cell Therapy Bemdaneprocel Shows Safety and Efficacy at 18 Months Posttreatment

March 22, 2024 - BlueRock Therapeutics’ bemdaneprocel (BRT-DA01), an investigational neuronal cell therapy intended to treat Parkinson disease (PD), has continued to show safety and promising initial results in terms of efficacy at 18 months posttreatment in patients who received the therapy in an ongoing phase 1 clinical trial (NCT04802733).

“It’s exciting that bemdaneprocel met safety and tolerability criteria at 12 months, and now the 18-month results suggest that these allogeneic cells survive and have potentially positive effects even after discontinuation of immunosuppressants,” Claire Henchcliffe, MD, the chair of the University of California, Irvine, School of Medicine Department of Neurology and a principal investigator for the trial, said in a statement. “We should not overinterpret results of a phase 1 study, but this is a promising step that deserves to be followed up with further studies.”

At 18 months posttreatment, the patients treated at the high dose experienced a mean increase from baseline of 2.7 hours in the “ON” state and a 2.7 hour decrease for time in the “OFF” state. For patients treated at the low dose, a mean increase of 0.2 hours in the “ON” state compared to baseline was observed at 18 months posttreatment, with a corresponding mean decrease of 0.8 hours spent in the “OFF” state.

Cardiac Function Preserved in Long-Term Follow-Up of Patients Treated With Duchenne Muscular Dystrophy Gene Therapy SGT-001

March 6, 2024 - Patients treated with SGT-001, Solid Biosciences’ investigational microdystrophin gene therapy for Duchenne muscular dystrophy (DMD), in the phase 1/2 IGNITE-DMD study (NCT03368742) showed preservation of cardiac function as they aged.

“This is the first study that describes longitudinal cMRI findings in DMD subjects that have received micro-dystrophin gene therapy,” first author Stephanie Salabarria, BHSc, a clinical research coordinator III at the University of Florida, and colleagues wrote. “We observed that cardiac function was preserved as the individuals age with expected worsening of DMD-related cardiomyopathy. Further studies are needed to better understand the effects of the DMD gene therapy in the heart and carefully quantify the extent of cardiac gene transfer.”

Most patients’ left ventricular end diastolic volume (LVEDV) remained normal throughout the study, ranging from 56 to 108 mL/m2 (median, 67.2 mL/m2). Similarly, ejection fraction (EF) also stayed in the normal range, ranging from 51% to 72% (median, 61.8%). One patient, who had a 94.7 mL/m2 LVEDV at baseline, had a 118.76 mL/m2 LVEDV at year 5 (Y5). This patient showed a decrease in left ventricular EF from a baseline of 53.8% to 39% at Y5.

Patients With Spinal Muscular Atrophy Who Required Tracheostomies Show Motor Function Improvements in Real World Setting After Treatment With Zolgensma

March 5, 2024 - Patients with spinal muscular atrophy (SMA) who also required tracheostomies and were treated with disease-modifying treatments (DMTs) including onasemnogene abeparvovec (Zolgensma; Novartis), a marketed adeno-associated virus vector (AAV)-based gene therapy, showed improvements in motor function, in addition to safety outcomes consistent with Zolgensma’s known safety profile.

“Clinically meaningful motor function improvements were observed independent of DMT types received before or after Zolgensma administration and most patients were still alive at the end of follow-up in this analysis. TEAEs were consistent with the established safety profile of Zolgensma suggesting that, unlike previously reported, a greater risk of TEAEs was not observed in this small sample of patients with tracheostomies. Cumulatively, these data support the DMT administration can provide improvements in motor function for patients with SMA who received tracheostomies,” first author Laurent Servais MD, PhD, a professor of paediatric neuromuscular Disease at the University of Oxford, and colleagues wrote.

Real-world data from the noninterventional RESTORE registry (NCT04174157) included 18 patients who had available motor milestone data based on any assessment, 16 patients of which (88.9%) achieved or maintainedmotor milestones during the observation period. Clinically meaningful score improvements were seen in 13 of 17 patients (76.5%) who had Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) scores. The change in CHOP INTEND score per month ranged from –1.0 to 4.0 (median, 0.43).

Gene Therapy Improves Functional Measures in XLRP

March 14, 2024 - Patients with X-linked retinitis pigmentosa (XLRP) treated with AGTC-501 gene therapy experienced improvements in visual function including retinal sensitivity as assessed by macular Integrity Assessment (MAIA) microperimetry and full-field stimulus threshold (FST) with a favorable benefit-risk profile.

“The benefit-risk profile is favorable and supports continued clinical development for the treatment of patients with XLRP caused by RPGR mutations,” Mark Pennesi MD, PhD, Director, Ophthalmic Genetics Retina Foundation Dallas, and Texas Professor of Ophthalmology Professor of Molecular and Medical Genetics, Paul H. Casey Ophthalmic Genetics Division Casey Eye Institute, Oregon Health & Science University, said. “To date, AGTC-501 data show robust improvements in visual function including retinal sensitivity as assessed by MAIA microperimetry and FST,” Pennesi said.

Seventeen percent of patients in the low-dose cohort and 63% of the high-dose cohort achieved at least a 7 dB improvement from baseline in at least loci at month 12. Patients in the high dose cohort also had improvements in baseline mean sensitivity in MAIA. These patients also showed statistically significant improvements in their treated eyes on Red and White light FST compared to both the low dose and the untreated control eyes, with a strong trend in blue light FST.

RGX-202 Gene Therapy Reduces CK, Yields Detectable Microdystrophin in Patients With DMD

March 4, 2024 - RGX-202 investigational gene therapy was well-tolerated, reduced creatine kinase (CK) levels and produced detectable microdystrophin in patients with Duchenne muscular dystrophy (DMD).

“The absence of functional dystrophin results in muscle cell damage during contraction, inflammation, fibrofatty replacement of muscle tissue, and ultimately cell death,” Aravindhan Veerapandiyan, MD, assistant professor, pediatric neurology, University of Arkansas, and colleagues wrote in their poster. “This reflects clinically in progressive weakness of skeletal muscle, eventual loss of ambulation, and weakness of cardiac muscle and the diaphragm which can present as cardiomyopathy and respiratory failure.”

The therapy has been well-tolerated in patients with DMD with no significant serious adverse events. Biomarker data were available for 3 participants, with ages 4.4, 10.5, and 6.6 years at dosing. These patients had Western Blot expression of 38.8%, 11.1%, and 83.4% of normal at 3 months, respectively, and CK level reductions of –43%, -44%, and –93% from baseline at 10 weeks.