Data Roundup: May 2024 Features Updates from ASGCT in Rare Neurological, Retinal Diseases, and more.


Catch up on any of the key data updates you may have missed last month, with coverage highlights from the CGTLive™ team.

Last month, May 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 American Society of Gene and Cell Therapy Annual Meeting across rare, inherited retinal, and even infectious diseases. Our team has highlighted these and other updates below.

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

SPG50 Gene Therapy Warrants Further Study for Spastic Paraplegia

May 8, 2024- MELPIDA (AAV9/AP4M1; Elpida Therapeutics) gene therapy has been well-tolerated in patients with hereditary spastic paraplegia, type 50 (SPG50).

“Our approach utilizes early intervention and higher intrathecal AAV doses than are used in most other intrathecal AAV clinical trials. We speculate that the self-complimentary design of the vector contributes to its potential efficacy, and the relatively modest strength UsP promoter contributes to its safety,” Souad Messahel, BS, MS, PhD, head, clinical operations, Elpida Therapeutics, and colleagues wrote in their poster.

MELPIDA has had a positive safety profile so far, with no negative immune responses and a manageable safety profile, as measured by MRI brain and spine scans, cerebral spinal fluid analysis, complete blood profiles, EKGs, and nerve conduction studies. There has been no evidence of dorsal root ganglion toxicity and nerve conduction was stable or improved after treatment.

NGGT Biotechnology’s Gene Therapy NGGT001 Improves Vision in Patients With Bietti’s Crystalline Dystrophy

May 9, 2024- Next Generation Gene Therapeutics (NGGT) Biotechnology’s NGGT001, an investigational adeno-associated virus (AAV) vector-based gene therapy intended to treat Bietti’s crystalline corneoretinal dystrophy (BCD), improved the vision of patients treated in 2-site investigator-initiated trial (NCT06302608).

“BCD is caused by mutations in the cytochrome P450 (CYP) family 4 subfamily V member 2 gene (CYP4V2) encoding a polyunsaturated fatty acid hydroxylase which is dominantly expressed in retinal pigment epithelium cells in the retina,” cofirst author Xiuju Chen, of the Xiamen Eye Center of Xiamen University and colleagues wrote in the poster’s abstract.“There has not been any treatment available for BCD. NGGT Biotechnology has developed NGGT001, an rAAV2-based vector expressing codonoptimized human CYP4V2 for treating BCD.”

In terms of safety, NGGT001 was deemed well-tolerated. One of the treated patients experienced 2 ocular treatment-emergent adverse events (TEAEs), a case of conjunctival edema and a case of eyelid edema, both of which resolved in 5 days and were deemed definitely not related to NGGT001. Several nonocular TEAEs were also observed among patients treated in the study. These included 2 cases of upper respiratory tract infection in a single patient, a case of calcaneal stress fracture in a different patient, and a case of pharyngitis in yet another patient.

Elevidys Shows Slight Statistical Improvements on Time to Rise, 10-Meter Walk/Run Despite NSAA Fail

May 10, 2024- While Sarepta’s phase 3 EMBARK trial (NCT05096221) of delandistrogene moxeparvovec (Elevidys, SRP-9001) gene therapy has failed its primary endpoint, primary data from the trial demonstrate some small, but statistically significant differences from placebo in key secondary endpoints in participants with Duchenne muscular dystrophy (DMD).

“What's really going to tell the story is as these patients are followed over longer periods of time. There’s a lot of challenges in showing efficacy, even with something that may be fairly efficacious, over such a short period of time,” coauthor Damon Asher, MS, PhD, senior director, global medical affairs, Sarepta Therapeutics, told CGTLive during the conference.

The trial’s primary endpoint, change in NSAA total score from baseline compared with placebo was not met, as previously announced. However, key secondary endpoints of change in time to rise (TTR) and time to walk/run 10 meters (10MWR) had small but significant differences from placebo, with a least square mean (LSM) difference of -.964 seconds (standard error [SE], 0.21; P = .0025) on TTR and an LSM of -0.42 seconds (SE, 0.15; P = .0048) on 10MWR. A composite, prespecified global statistical test including NSAA, TTR, 10MWR, Stride Velocity 95th Centile, 100MWR, and ascend 4 steps test was statistically significant compared with placebo (P = .0044)

Multicharacteristic Opsin Gene Therapy Improves BCVA, MLSDT in Retinitis Pigmentosa

May 14, 2024- Patients with retinitis pigmentosa (RP) treated with high dose MCO-010 gene therapy had statistically significant improvements on best-corrected visual acuity (BCVA) and near-field object recognition from baseline compared with those who received sham injections.

“RP stands as the most prevalent inherited retinal disease globally, impacting over 1.5 million individuals worldwide. With over 90 identified genetic mutations linked to RP, the absence of effective treatments underscores the substantial unmet need,” Samuel Barone, MD, chief medical officer, Nanoscope Therapeutics, and colleagues wrote in their poster.

On BCVA, the low dose cohort had mean improvements of 0.160 (P against sham =.2767), 0.191 (P = .1945), 0.431 (P = 0.0058), and 0.332 LogMAR (P = .0290) at weeks 16, 24, 36, and 52, respectively. The high dose cohort had mean improvements of 0.022 (P against sham = .8403), 0.197 (P = .0772), 0.214 (P = .0549), and 0.287 (P = .0104) at weeks 16, 24, 36, and 52, respectively.

CRISPR-Editing EBT-101 Therapy Safe, Temporarily Suppresses HIV Infection

May 21, 2024- Excision BioTherapeutics’ EBT-101-001 phase 1/2 trial (NCT05144386) of EBT-101 CRISPR-based gene editing therapy has met its primary safety endpoint and its secondary biodistribution/immunogenicity endpoint.

“Initial data from the EBT-101-001 trial provides important clinical evidence that a gene editing treatment modality can be safely delivered for targeting the HIV DNA reservoirs in human cells. This study provides researchers with invaluable insights for how CRISPR technology can be applied for addressing infectious disease and was an important first step towards additional programs designed to optimize this treatment modality for treating the millions of individuals who are impacted by HIV and other infectious disease,” principal investigator Rachel M. Presti, MD, PhD, Professor of Medicine, Washington University School of Medicine, St. Louis, said in a statement

Investigators observed no serious adverse events (AEs), grade 1 AEs related to the therapy, and grade 1 or 2 AEs that resolved without treatment. Of the 5 participants who received a single infusion of the initial dose of EBT-101, 3 stopped antiretroviral therapy, experienced viral rebound, and had to restart antiretrovirals. One participant maintained viral suppression for 16 weeks after treatment discontinuation.

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