FDA accepts BLA for MCO-010 in retinitis pigmentosa

The US Food and Drug Administration (FDA) has accepted Nanoscope Therapeutics’ Biologics License Application (BLA) for sonpiretigene isteparvovec (MOGENRY), formerly MCO-010, an intravitreally delivered optogenetic gene therapy for adults with retinitis pigmentosa (RP) and severe vision loss.¹ The acceptance advances toward regulatory review for treatment that, if approved, would be positioned as the first mutation-agnostic therapy intended to restore useful vision in patients with RP regardless of the causative gene.¹

The therapy proposes to bypass the degenerated photoreceptor layer entirely and confer light sensitivity on surviving inner retinal neurons, using a single in-office intravitreal injection rather than genetic testing, subretinal surgery, or repeat dosing.¹

Regulatory pathway and trial basis

The BLA is supported principally by the RESTORE trial (NCT04945772), a multicenter, randomized, double-masked, sham-controlled study that enrolled 27 patients with advanced RP, randomizing 18 to intravitreal MCO-010 (across low- and high-dose arms) and 9 to sham injection.^2,3 Longer-term data from the ongoing REMAIN extension study (NCT06162585) were also submitted.¹

Efficacy was anchored on change in best-corrected visual acuity (BCVA), a low-vision endpoint the company has stated the FDA endorsed as appropriate for registration.³ At week 52, the high-dose arm showed a mean BCVA improvement of 0.337 logMAR versus sham (P = .021), a gain corresponding to roughly three lines and exceeding the 0.3-logMAR threshold generally regarded as clinically meaningful; the low-dose arm improved 0.382 logMAR (P = .029).³ At week 76, the high-dose arm sustained a 0.539-logMAR mean gain (P = .001), and longitudinal analysis reported significant separation from sham across weeks 36 through 88.⁴ Composite functional measures combining multi-luminance mobility (MLYMT) and shape-discrimination (MLSDT) testing were also reported, with the company describing an approximately 89% response rate at 12 months.²

On safety, no treatment-related serious adverse events were reported in the MCO-010 arms over two years.^1,4 The most common ocular findings were anterior chamber inflammation (approximately 44%) and elevated intraocular pressure (approximately 39%), described as mild to moderate and manageable with topical therapy.⁴

Clinical context and unmet need

RP is a group of inherited retinal dystrophies characterized by progressive rod-then-cone photoreceptor degeneration, with an estimated prevalence near 1 in 4000 and marked genetic heterogeneity spanning dozens of causative genes.⁵ Nanoscope estimates RP affects more than 100,000 people in the US, of whom more than 25,000 are legally blind.¹ Apart from vitamin A supplementation and management of complications, no therapy halts or reverses vision loss for the large majority of patients, and disease-modifying options remain limited for those with advanced disease.⁵

Drug and drug-class background

MCO-010 delivers a multi-characteristic opsin gene to retinal bipolar cells via an adeno-associated viral vector, rendering those cells directly responsive to ambient light and thereby substituting for lost photoreceptor input.¹ Because the approach targets surviving inner retinal neurons rather than correcting a specific mutation, it is intended to be gene-agnostic—a distinction from the only currently approved ocular gene therapy, voretigene neparvovec (Luxturna), which the FDA approved in 2017 for the narrower population of patients with confirmed biallelic RPE65-mediated inherited retinal dystrophy.⁶ MCO-010 has received FDA Fast Track and Orphan Drug designations for RP and Orphan Drug and Regenerative Medicine Advanced Therapy designations in Stargardt disease.¹

Interpretive framing

The data are notable for advanced RP, where controlled evidence of measurable visual improvement has historically been scarce, and the intravitreal, in-office delivery could lower practical barriers to adoption relative to surgical gene therapy.^1,3 SriniVas Sadda, MD, framed durability as the salient feature, stating that "what sets MOGENRY apart is a meaningful benefit, with evidence of sustained effect for years," while Allen C. Ho, MD, the company's chief medical advisor, noted that avoiding genetic testing and a surgical suite "could enable broad adoption by community retina practices."¹

REFERENCES

1. Nanoscope Therapeutics announces US Food and Drug Administration acceptance of Biologics License Application for MOGENRY for the treatment of retinitis pigmentosa with severe vision loss. PR Newswire. September 9, 2026. https://www.prnewswire.com/news-releases/nanoscope-therapeutics-announces-us-food-and-drug-administration-acceptance-of-biologics-license-application-for-mogenry-for-the-treatment-of-retinitis-pigmentosa-with-severe-vision-loss-302873158.html

2. Nanoscope Therapeutics announces positive topline results from Phase 2b RESTORE trial of MCO-010 for treatment of retinitis pigmentosa. Ophthalmology Times. https://www.ophthalmologytimes.com/view/nanoscope-therapeutics-announces-positive-topline-results-from-phase-2b-restore-trial-of-mco-010-for-treatment-of-retinitis-pigmentosa

3. MCO-010 Phase 2b data supports BLA submission for retinitis pigmentosa. CGTLive. https://www.cgtlive.com/view/mco-010-phase-2b-data-supports-bla-submission-retinitis-pigmentosa

4. Nanoscope presented positive 2-year randomized, controlled trial results of MCO-010 for retinitis pigmentosa. PR Newswire. October 2024. https://www.prnewswire.com/news-releases/nanoscope-presented-positive-2-year-randomized-controlled-trial-results-of-mco-010-for-retinitis-pigmentosa-302293414.html

5. Fahim AT, Daiger SP, Weleber RG. Nonsyndromic retinitis pigmentosa overview. In: GeneReviews. University of Washington, Seattle. https://www.ncbi.nlm.nih.gov/books/NBK1417/

6. FDA announces landmark approval of gene therapy for inherited retinal dystrophies (voretigene neparvovec, Luxturna). American Academy of Ophthalmology. https://www.aao.org/education/headline/fda-announces-landmark-approval-of-gene-therapy-in

7. RESTORE study record. ClinicalTrials.gov identifier NCT04945772. https://clinicaltrials.gov/study/NCT04945772