SparingVision completes PRODYGY trial patient dosing with SPVN06

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SPVN06, a novel gene-agnostic adeno-associated virus (AAV) gene therapy designed to slow cone photoreceptor degeneration in retinitis pigmentosa (RP), has completed dosing in the multicenter Phase I/II PRODYGY trial, according to a recent company report.¹ This milestone marks an early safety and exploratory efficacy evaluation in a cohort of 33 adult patients with mid-stage RP, with initial results expected in 2027—an important timeline for clinicians tracking emerging disease-modifying strategies in inherited retinal dystrophies.¹

Retinitis pigmentosa remains a progressive, genetically heterogeneous group of retinal dystrophies that lead to photoreceptor loss and eventual vision impairment in adulthood. There are currently no broadly effective therapies that modify disease progression for most patients, underscoring the clinical interest in gene-based and neuroprotective approaches beyond the limited indications of existing treatments.^2,3

Trial Overview

The PRODYGY (Promising ROd-cone DYstrophy Gene therapY) study (NCT05748873) is a phase I/II, multicenter, open-label dose escalation and controlled extension trial evaluating safety, tolerability, and exploratory efficacy of SPVN06 in adult patients with RP due to mutations in RHO, PDE6A, or PDE6B genes.¹^,² SPVN06 was administered once via subretinal injection into the worse-seeing eye.¹

The trial was conducted in 2 parts:

• Step 1 (Dose Escalation): Nine patients received escalating doses (low, medium, and high) of SPVN06 across 3 cohorts under DSMB oversight; safety data from these cohorts demonstrated a generally favorable tolerability profile, enabling progression through all planned dose levels without reported dose-limiting toxicity.²˒³˒⁶
• Step 2 (Controlled Extension Phase): Twenty-four participants were randomized to receive high-dose (n=9), medium-dose (n=9), or no injection (control, n=6). This extension is intended to provide comparative data on exploratory endpoints, including functional (best-corrected visual acuity), anatomical (structural imaging measures), and quality-of-life outcomes over a minimum of 12 months of follow-up. The first safety outputs of this phase are anticipated to contribute to regulatory dialogue ahead of registrational trial planning.¹

Primary endpoint analysis across both parts is scheduled after all participants complete ≥12 months of follow-up, with an initial data readout expected in 2027.¹

Clinical Context and Unmet Need

RP affects approximately 1.5 million to 2 million individuals worldwide and encompasses a broad spectrum of inherited photoreceptor dystrophies, typically presenting with night blindness, constricted peripheral fields, and progressive reduction of visual acuity as rod loss advances and cones subsequently degenerate.²˒³˒⁴ Current management focuses on supportive care, genetic counseling, and low-vision rehabilitation.²

The only FDA-approved gene therapy for RP remains voretigene neparvovec (Luxturna), which is restricted to patients with confirmed biallelic RPE65 mutations—a small subset of the RP population.^2,3,4 No broadly applicable disease-modifying therapy has been validated across the genetic heterogeneity of RP.²˒³

Mechanism and Rationale

SPVN06 is an AAV-based gene therapy that delivers sequences encoding rod-derived cone viability factor (RdCVF) and its long form (RdCVFL), aiming to enhance cone survival and metabolic resilience in the degenerating retina. This gene-agnostic strategy targets cone photoreceptors irrespective of the specific upstream causative mutation, addressing a key challenge in RP given its extensive genetic diversity.^1,2,3 Preclinical data in rod-cone dystrophy models suggests that RdCVF expression may slow photoreceptor degeneration; nonhuman primate studies have shown favorable biodistribution and safety at clinically relevant vector doses.⁵

Interpretive Analysis

Completion of dosing in the PRODYGY study represents a procedural milestone in early clinical development but does not yet provide definitive evidence of efficacy. The safety/tolerability data reported to date are encouraging but limited by small cohort sizes and the absence of peer-reviewed disclosure of outcomes. Preliminary safety signals align with other AAV-mediated subretinal therapies, where procedural adverse events and mild inflammatory responses are recognized potential risks.^3,8 Continued follow-up and rigorous comparative analyses—including control arm outcomes—will be essential to discern meaningful functional benefit.

Comparison with other emerging RP therapies—including gene-specific approaches (e.g., RPGR-targeting vectors) and optogenetic or cell-based strategies—will depend on forthcoming efficacy data from PRODYGY and parallel trials.^2,3,4

Limitations and Future Directions

Key limitations include the relatively small sample size, short follow-up duration to date, and absence of published full datasets. The controlled phase’s untreated arm provides only rudimentary comparative data but may not capture long-term disease trajectories. Regulatory engagement planned for 2026 may clarify optimal endpoints for a pivotal study, but substantive evidence of sustained visual function preservation is required before broader clinical adoption can be considered.¹

References

1. SparingVision announces completion of dosing in Phase I/II PRODYGY trial of SPVN06 for RP. Press release. SparingVision; Dec 2025.

2. ClinicalTrials.gov. NCT05748873 PRODYGY: Promising ROd-cone DYstrophy Gene therapY. https://clinicaltrials.gov/study/NCT05748873. Accessed Feb 8, 2026.

3. SparingVision advances PRODYGY trial into Phase II after favorable DSMB review. Press release. SparingVision; Jan 21, 2025.

4. Wu KY, et al. Retinitis pigmentosa: novel therapeutic targets and drug delivery mechanisms. J Clin Med. 2023. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9963330/.

5. Preclinical safety and biodistribution of SPVN06 in rod-cone dystrophy models. Gene Therapy. 2025. https://www.nature.com/articles/s41434-025-00556-3.

6. Initial safety data from SPVN06 cohorts presented at Macula Society meeting. Retinal Degeneration Fund; Feb 8, 2024.

7. Pniakowska Z, et al. Genetic therapies for retinitis pigmentosa. J Clin Med. 2025.

8. SparingVision SPVN06 updates presented at ophthalmology conferences (safety data). SparingVision; Sep 23, 2024.