Data Roundup: March 2025 Features Updates from MDA's Conference, an Alzheimer Disease Trial, and More

Last month, March 2025, the CGTLive® team was diligently tracking the latest data readouts and published literature on cell and gene therapies within oncology, neurology, rare diseases, and more.

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 data updates from the 2025 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, held March 16-19 in Dallas, Texas and as well as some general data updates from clinical studies that came outside of medical meetings. Our team has highlighted these below.

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

Sarepta’s DMD Gene Therapy Elevidys Demonstrates Manageable Safety Across 5-Year Timespan

March 26, 2025 - Sarepta Therapeutics’ delandistrogene moxeparvovec-rokl (marketed as Elevidys), a marketed adeno-associated virus ( rAAVrh74) vector-based gene therapy intended to slow progression of Duchenne muscular dystrophy (DMD) through delivery of a microdystrophin transgene, showed consistent safety outcomes across a broad population of patients with the disease. The data, which come from pooled clinical trial results, were recently presented at the 2025 MDA Clinical & Scientific Conference.

Patients (n = 156) from 4 clinical trials were included in the pooled analysis—Study 101 (NCT03375164), Study 102 (NCT03769116), ENDEAVOR Cohorts 1-5b (NCT04626674), and EMBARK Part 1 (NCT05096221). The patients had up to 5 years of follow-up as of January 15, 2024. The pooled group had an age range of 3.2 to 20.2 years (mean, 6.7 years) and the mean weight for the group was 24.6 kg (range, 12.5-80.1 kg). Patients who were ambulatory at baseline constituted 95% (n = 148) of the total group.

Treatment-related, treatment-emergent adverse events (TR-TEAEs) were most often observed in the 90 day window after administration of the gene therapy. The most common TR-TEAEs, reported in at least 15% of patients, included vomiting, nausea, decreased appetite, increased glutamate dehydrogenase levels, and upper abdominal pain, according to Jerry Mendell, MD, advisor to the Jerry R. Mendell Center for Gene Therapy, who presented the findings. Notably, spontaneous resolution or resolution after appropriate management was observed for most of these events.

REGENXBIO’s DMD Gene Therapy RGX-202 Generates Microdystrophin Expression in Additional Patients Treated in Phase 1/2 Trial

March 20, 2025 - REGENXBIO’s RGX-202, an investigational adeno-associated virus (AAV) vector-based gene therapy intended to treat Duchenne muscular dystrophy (DMD), has continued to demonstrate the ability to produce microdystrophin at “consistent, robust” levels in data from 2 new patients treated in the phase 1/2 portion of the AFFINITY DUCHENNE clinical trial (NCT05693142). The results were presented at the 2025 MDA Clinical & Scientific Conference by Fei Cao, the medical program lead at Genethon.

One of the patients, who was aged 3 years at the time of treatment, achieved 122.3% microdystrophin expression compared to control. In the other patient, who was treated at 7 years of age, microdystrophin expression was found to be 31.5% compared to control.

Furthermore, REGENXBIO reported that in all patients RGX-202 was localized to the sarcolemma, as intended. The company also stated that in patients aged 8 years of age and older who are ambulatory, microdystrophin expression has been reported at levels higher than other approved or investigational DMD gene therapy products. In addition, REGENXBIO noted that on qPCR RGX-202 demonstrates vector genome copies from 4.9 to 55.4, which are the highest reported across approved and investigational DMD gene therapy products.

Novartis’ OAV101 IT Improves or Stabilizes Motor Function in Patients With Spinal Muscular Atrophy

March 19, 2025 - Novartis’ OAV101 IT, an investigational intrathecally-delivered version of the marketed gene therapy onasemnogene abeparvovec (Zolgensma), has demonstrated the ability to improve patient scores on the Hammersmith Functional Motor Scale Expanded (HFMSE). The data, which come from the phase 3 STEER clinical trial (NCT05089656), were presented at the 2025 MDA Clinical & Scientific Conference.

The STEER study includes treatment-naive children aged 2 to less than 18 years who could sit but had not ever walked independently, and evaluated OAV101 IT against a placebo procedure. It was found that patients who received the gene therapy (n = 75) achieved a 2.39-point improvement on the HFMSE, whereas those who received the placebo (n = 51) showed only a 0.51 point improvement on the HFMSE (P=0.0074); as such, STEER met its primary end point. Novartis pointed out that results for the secondary end points did not reach statistical significance because of the preplanned multiple testing procedure, but that these findings “consistently favor” OAV101 IT. Patients in the treatment group were aged 2.1 to 16.6 years (mean, 5.89) and patients in the placebo group were aged 2.4 to 14.2 years (mean, 5.87)

With regard to safety, adverse events (AEs), serious AEs (SAEs), and AEs of special interest were reported to have a similar incidence between the treatment group and the placebo group. Upper respiratory tract infection and pyrexia constituted the most common AEs in both groups. Pneumonia and vomiting constituted the most common SAEs in patients who received the gene therapy, whereas pneumonia and lower respiratory tract infection constituted the most common SAEs in patients who received the placebo. Novartis stated that increased transaminase cases did not occur frequently, and those cases that did occur were for the most part transient and low grade. Hy’s law cases did not occur in any patients.

Longeveron's Cell Therapy Lomecel-B Improves Cognitive Function in Mild Alzheimer Disease

March 13, 2025 - New data from the now-completedphase 2a CLEAR MIND trial (NCT05233774), which is evaluating Longeveron's allogeneic bone marrow-derived medicinal signaling cell (MSC) formulation Lomecel-B (also known as laromestrocel) for the treatment of mild Alzheimer disease (AD), have been published in Nature Medicine. Among the findings reported were improvements in cognitive function, quality of life, and brain volume.

The study included 48 patients, 36 of whom received laromestrocel and 12 of whom received a placebo. Longeveron reported that laromestrocel treatment was associated with a slowing in cognitive and functional decline. This finding was informed by statistically significant data from the Montreal Cognitive Assessment, as well as statistical trending improvements, made with comparison to the placebo group, on the Clinical Dementia Rating – Sum of Boxes (CDR-SB) and Mini-Mental State Examination (MMSE). Furthermore, Longeveron noted that on the Composite Alzheimer’s Disease Score (CADS), an improvement from baseline at 39 weeks posttreatment was recorded.

In addition, the company stated that on the Alzheimer’s Disease Cooperative Study Activities of Daily Living (ADCS-ADL), a statistically significant improvement was seen for the laromestrocel group in relation to the placebo group. Statistically significant data indicating that total brain volume, hippocampus volume, temporal and frontal lobe volumes, and thalamus volume losses had been minimized in the laromestrocel group compared to the placebo group were also noted. Improvements for the laromestrocel group in comparison to the placebo group were also observed on the the Alzheimer’s Disease Related Quality of Life (ADRQOL) and Quality of life AD (QOL-AD) scales.

Stem Cell Therapy CALEC Restores Corneal Damage in Trial Led by Massachusetts Eye and Ear Investigators

March 7, 2025 - A therapy known as cultivated autologous limbal epithelial cells (CALEC) transplantation showed over 90% partial and complete success rates in repairing the corneal surfaces that had corneal damage believed to be irreversible, according to data from a phase 1/2 clinical trial (Clinicaltrials.gov registration: NCT02592330) that was published in Nature Communications. The study is led by investigators at the Massachusetts Eye and Ear in Boston, including Ula Jurkunas, MD, PhD, who is associate director of the Cornea Service at the Mass Eye and Ear and professor of Ophthalmology at Harvard Medical School, Boston.

According to the investigators, the clarity of the cornea is dependent upon the regenerative capacity of the limbal epithelial stem cells. These cells are found in the corneal limbus and continuously provide specialised corneal epithelium while serving as a barrier between the conjunctiva and cornea. Conjunctivalisation of the corneal surface and other signs of diminished integrity of the corneal epithelium, such as neovascularisation, inflammation, scarring and opacity, which lead to decreased vision and debilitating symptoms such as pain, photophobia, and tearing, characterize limbal stem cell deficiency (LSCD). Reestablishing a healthy ocular surface and adjacent limbal niche to support limbal epithelial stem cells is the objective of treatment intended to manage LSCD.