"We observed significant vision restoration in many patients with severe vision loss, including those who were completely blind," said David Boyer, MD an investigator in the trial and Adjunct Clinical Professor of Ophthalmology at the University of Southern California Keck School of Medicine. "Many patients treated with MCO-010 derived a clinically meaningful benefit measurable on the primary visual function test, and this effect was confirmed by a parallel improvement in functional vision assessments. If approved, MCO-010 is poised to make a positive, meaningful impact on the lives of patients affected by this debilitating condition."
Based on these results, Nanoscope intends to submit a BLA to the U.S. FDA in the second half of 2024 as the first step in executing its global regulatory and commercialization strategy.
"I am thrilled to see that MCO-010 has the potential to improve vision in patients with advanced RP," said Arshad M. Khanani, MD, MA, FASRS, Director of Clinical Research at Sierra Eye Associates and Clinical Professor at the University of Nevada, Reno School of Medicine. "This is a pivotal moment for the field of ocular gene therapy to have a potential intravitreal mutation-agnostic treatment for RP, a disease that has no available treatment currently and leads to permanent vision loss."
"Nanoscope is at the forefront of advancing optogenetics into a tangible therapeutic solution for patients with RP," said Sulagna Bhattacharya, co-founder and Chief Executive Officer of Nanoscope. "The compelling data from the most recent analyses of the RESTORE trial at week 76 provide additional validation of Nanoscope's versatile MCO platform, which is driving our expanding pipeline of programs in both Stargardt disease and geographic atrophy (GA) due to age-related macular degeneration (AMD). We extend our heartfelt appreciation to the trial participants and their families, as well as to the investigators and all those who contributed to this groundbreaking trial and its successful completion."
These results represent the first evidence of effectiveness of a mutation-agnostic gene therapy for a genetic disease. These results reflect more than a decade of innovation across all aspects of the MCO-010 program, including vector design, manufacturing, and clinical trial design, as well as the development of novel functional vision endpoints for this population with severe vision loss.
"These results are the culmination of more than a decade of work by numerous dedicated individuals, underscoring the potential of our unique broadband, highly photosensitive, and rapid MCO-010 platform," said Samarendra Mohanty, PhD, co-founder, President, and Chief Scientific Officer of Nanoscope. "This achievement marks a significant milestone in the field of mutation-agnostic gene therapy, firmly establishing the promise of optogenetics as a therapeutic modality. We extend our sincere gratitude to the National Eye Institute-NIH and collaborators for their invaluable contributions in realizing the therapeutic potential of MCO therapy, offering hope for vision restoration to patients regardless of their underlying genetic mutation."
RESTORE Trial Detail
The multicenter, Phase 2b trial randomized 28 subjects with severe vision loss and confirmed clinical diagnosis of RP. One randomized subject, who withdrew consent before baseline measurements and study intervention, was not included in the mITT population. Reported results are from the mITT population that included all randomized subjects who received the intervention in the study eye (MCO-010 or control): 18 subjects in the MCO-010 groups and 9 subjects in the control group. For the primary and key secondary endpoints, subjects were evaluated at multiple time points over two years to assess BCVA, measured by the Freiburg visual acuity test.
- A linear mixed-effects model for repeated measures (MMRM) was performed on the primary and key secondary endpoints, where the visual acuity data from all post-baseline visits was included in the model, with baseline visual acuity as a covariate.
- Comparisons between the treatment groups were performed using a Hochberg procedure to adjust for multiple comparisons against the control. Using the results obtained from the MMRM model, the p-values from the two comparisons of the MCO-010 groups versus the control were ordered from largest to smallest.
- Primary and key secondary visual acuity endpoint results being reported are based on regulatory discussions, as previously announced on January 18, 2024, and align the study endpoints with the originally intended study objectives. A revised statistical analysis plan (SAP) was finalized and submitted to regulators before the completion of week 76 and later time points of the study.
- The functional vision was assessed by evaluating subject performance in object recognition or navigating a mobility course under a variety of light levels encountered in activities of daily living.
A summary of top-line efficacy results follows:
| |
Primary endpoint: BCVA at Week-52
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Key secondary endpoint: BCVA at Week-76
|
|
Change in LogMAR from
Baseline (Mean ± SEM)
|
P-Value
vs Control
|
Change in LogMAR from
Baseline (Mean ± SEM)
|
P-Value
vs Control
|
|
High dose MCO-010
(1.2E11 gc, N=9)
|
-0.337 ±0.0829
|
0.0209
|
-0.539 ± 0.1032
|
0.0014
|
|
Low dose MCO-010
(0.9E11 gc, N=9)
|
-0.382 ±0.1244
|
0.0290
|
-0.374 ± 0.1332
|
0.0652
|
|
Sham control
(N=9)
|
-0.050 ±0.0717
|
----
|
-0.078 ± 0.0737
|
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|
About Retinitis Pigmentosa
Retinitis Pigmentosa (RP) encompasses a group of rare genetic disorders in which the retina's photoreceptor cells degrade over time, leading to impaired vision and eventual blindness. These disorders are believed to be linked to over 100 different gene mutations. Approximately 100,000 people in the U.S. and an estimated 2 million people worldwide suffer from RP, making it the leading cause of inheritable blindness.
About MCO-010
Current gene therapies aim to treat patients with specific genetic mutations and are further limited in advanced diseases with degenerated outer retina cells. Ambient-light activatable MCO optogenetic monotherapy targets abundant inner retinal neurons and has the potential to restore vision permanently lost due to advanced RP. MCO-010 (sonpiretigene isteparvovec, suspension for intravitreal injection) is the only broadband, fast, and highly light-sensitive opsin currently in clinical trials. With bipolar cell targeting via mGluR6 promoter-enhancer, the MCO-010 expression cassette is designed for restoring high-quality vision in real-world environments. The proprietary AAV2 vector allows robust transduction of MCO-010 in bipolar cells upon intravitreal injection. The Phase 1/2a study of MCO-010 in advanced RP patients demonstrated favorable safety and dose-dependent improvement in visual acuity.
About Nanoscope Therapeutics Inc.
Nanoscope Therapeutics is developing gene-agnostic, sight-restoring optogenetic therapies for the millions of patients blinded by inherited retinal diseases, for which no cure exists. The company's lead asset, MCO-010, recently completed the RESTORE Phase 2b multicenter, randomized, double-masked, sham-controlled clinical trial in the U.S. for retinitis pigmentosa (NCT04945772). The company has also recently completed the Phase 2 STARLIGHT trial of MCO-010 therapy in patients with Stargardt disease (NCT05417126 ). MCO-010 has received FDA fast-track designations and FDA orphan drug designations for both RP and Stargardt disease. Preclinical assets include non-viral laser-delivered MCO-020 gene therapy for GA due to AMD.
Read the full press release here.