Data Roundup: January 2025 Features Updates for Sarepta's Elevidys in DMD, Tenaya's Hypertrophic Cardiomyopathy Gene Therapy, and More

Last month, January 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 for Sarepta Therapeutics' delandistrogene moxeparvovec-rokl (marketed as Elevidys) in Duchenne muscular dystrophy (DMD), Tenaya Therapeutics’ hypertrophic cardiomyopathy (HCM) gene therapy TN-201, and more. 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 Shows Sustained Benefit in Updated Phase 3 Data

January 29, 2025 - Sarepta Therapeutics’ delandistrogene moxeparvovec-rokl (marketed as Elevidys), a marketed adeno-associated virus (AAV) vector-based gene therapy for patients with DMD, has shown sustained benefit in patients who are ambulatory who were treated in the phase 3 EMBARK clinical trial (NCT05096221; SRP-9001-301), according to new results from part 2 of the study.

Among 59 patients in part 2 who crossed over to receive treatment with Elevidys after having received the placebo in part 1 of the study, a least square means (LSM) improvement of +2.34 points from baseline on the North Star Ambulatory Assessment (NSAA) in comparison to a matched external controlgroup (EC) at 52 weeks posttreatment (P < .0001). In addition, the patients treated with Elevidys in part 2 also showed an LSM –2.70 seconds improvement on Time to Rise (TTR) (P < .0001) and an LSM –1.07 seconds improvement on 10-meter walk/run (10MWR) (P = .0001) in comparison to a prespecified, propensity-weighted EC. Sarepta noted that the study remained blinded during the 52 weeks posttreatment period in part 2 and that the cross-over treated patients had an average age of 7.18 years, whereas the patients treated in part 1 of the study had had an average age of 5.98 years.

Sarepta also reported updated 2 year results from the 63 patients who originally received Elevidys in part 1 of EMBARK. At 2 years posttreatment, the patients treated with the gene therapy in EMBARK showed an LSM improvement of +2.88 points on NSAA (P =. 0001), -2.06 seconds on TTR (P = .0033), and –1.36 seconds on 10MWR (P =.0028) in comparison to EC. The company pointed out that an increased difference from 1 year posttreatment to 2 years posttreatment on NSAA, TTR, and 10MWR was observed between patients treated with Elevidys in part 1 and the EC, suggesting a continued widening of the chasm in disease trajectory between patients who received the gene therapy and the natural history course of the disease.

Tenaya’s Hypertrophic Cardiomyopathy Gene Therapy TN-201 Well-Tolerated in Early Clinical Data

January 9, 2025 - Tenaya Therapeutics’ TN-201, an investigational AAV-vector based gene therapy, has been well-tolerated and shown early signs of efficacy in data reported from the phase 1b MyPeak-1 clinical trial (NCT05836259) evaluating it for the treatment of hypertrophic cardiomyopathy (HCM) caused by mutations in the MYBPC3 gene.

The data comes from 3 patients treated at the trial’s low dose (3x10¹³ vg/kg), 1 of whom has 52 weeks of follow-up (patient 1), 1 of whom has 40 weeks of follow-up (patient 2), and 1 of whom has 12 weeks of follow-up (patient 3). In these patients there were no cardiac toxicities, complement activation-associated adverse effects, or thrombotic microangiopathy (TMA)-related events reported. Isolated elevations in liver enzymes associated with treatment were observed, but were managed with corticosteroids; no other signs of liver damage were seen in association with these elevations. A single grade 1 case of mild, asymptomatic enzyme elevation was managed with a corticosteroid bolus in a hospital and thus was considered to be a serious adverse event (SAE). Generally, AEs that occurred during the study were mild, transient, or reversible and the majority of AEs associated with treatment were typical of AAV vector-based gene therapy or immunosuppressive regimens. Two SAEs deemed unrelated to TN-201 occurred. Tenaya noted that all 3 patients remain on study and that patient 1 and patient 2 have tapered off their immunosuppressive regimens.

With regard to signs of efficacy, at 8 weeks posttreatment cardiac transduction was seen in patients 1 and 2 at levels above those considered effective in mouse model research. Furthermore, patients 1 and 2 showed levels of TN-201-derived mRNA at 8 weeks posttreatment that were considered similar to those that have been observed in other clinical-stage gene therapies for cardiac disease; although, it was noted that these levels were lower than what was observed in preclinical research. In patient 1, TN-201 mRNA expression showed an increase of 50% at 52 weeks posttreatment. In addition, patient 1 showed a 3% increase in total levels MyBP-C, the disease-targeted protein encoded by TN-201, at 52 weeks posttreatment compared to 8 weeks posttreatment.

NGGT Biotechnology’s Gene Therapy NGGT001 Continues to Show Encouraging Safety in Bietti’s Crystalline Dystrophy

January 22, 2025 - Next Generation Gene Therapeutics (NGGT) Biotechnology’s NGGT001 (also known as rAAV2-hCYP4V2), an investigational AAV vector-based gene therapy intended to treat Bietti’s crystalline dystrophy (BCD), did not show any substantial safety concerns in updated data from an early phase 1 investigator-initiated trial (NCT06302608).

The trial, which treated 12 patients across 2 trial sites in China, utilized 2 dose levels: 1.5x10¹¹ and 3.0x10¹¹ total vector genomes of NGGT001. Six patients were treated at the lower dose, and 6 were treated at the higher dose.

At 12 months of follow-up, there were no dose-limiting toxicities and no severe adverse events (AEs) related to the treatment reported. A mild case of intraocular inflammation occurred in 1 patient, but speedily resolved.

Ocugen’s Retinitis Pigmentosa Gene Therapy OCU400 Sustains or Improves Visual Function in 2-Year Follow-Up Data

January 13, 2025 - Ocugen’s OCU400, an investigational gene therapy product based on the company’s Modifier Gene Therapy Platform, has demonstrated the ability to sustain or improve visual function in comparison to untreated eyes in patients treated in a phase 1/2 clinical trial (NCT05203939) in retinitis pigmentosa (RP), according to newly announced 2-year follow-up data.

Among 9 patients treated in the study who were evaluable at 1 year and 2 years posttreatment, all 9 (100%) showed improved or preserved visual function in comparison to their untreated fellow eyes at both time points. Furthermore, all 9 evaluable patients (100%) showed improvement or stabilization on mobility testing at 1 year posttreatment; mobility testing was not carried out again after this time point. Notably, at 2 years posttreatment, the improvements recorded in visual function compared to untreated fellow eyes were determined to be statistically significant (P = .01) without regard to the underlying mutation causing the patient’s RP.

RP is associated with over 100 genes. Because of the wide range of genes implicated in the condition, it is unlikely to be feasible for gene therapy approaches targeted at each specific gene to be developed and commercialized in a reasonable amount of time. In order to work around this issue, Ocugen developed its Modifier Gene Therapy Platform, which is intended to allow for a gene-agnostic approach to treating IRDs.