Nanoscope Therapeutics Inc. released positive topline data from the RESTORE phase 2b trial evaluating the use of MCO-010 as an optogenetic therapy for the treatment of retinitis pigmentosa (RP).
Let’s begin with this company.
Founded in 2017 and headquartered in Dallas, Texas, the biotechnology company is developing gene-agnostic, sight-restoring optogenetic therapeutics for inherited retinal diseases (IRDs).
Included in its investigational candidate pipeline are gene therapies that deliver light sensitive multi-characteristic opsins (MCOs), with the intent to treat the following IRDs:
- RP (our topic of discussion)
- Candidate: MC-010
- Stargardt disease
- Candidate: MCO-010
- Dry age-related macular degeneration (AMD)
- Geographic atrophy (GA)
- Candidate: Optogenetics non-viral
- Geographic atrophy (GA)
- Usher syndrome
- Cone rod dystrophy
Now refresh me on MCO-010.
MCO-010 (sonpiretigene isteparvovec) is an ambient-light activatable MCO optogenetic agent, formulated as a single intravitreal injection.
How it works: The gene therapy vector serves to reprogram healthy retina cells, making them photosensitive.
By using proprietary adeno-associated virus serotype 2 (AAV2) and promoter technology, it delivers the MCO genes into retinal bipolar cells to enable vision in different color environments.
The intent: to potentially restore vision with enhanced contrast and definition in real-world environments for patients with advanced RP.
And its clinical status?
The FDA has already granted MCO-010 both Orphan Drug and Fast Track designations for RP and Stargardt disease; it’s also currently the only broadband, fast, and most-light sensitive opsin in clinical trials.
Gotcha. Now talk about this trial.
The randomized, double-masked, sham-controlled, multicenter phase 2b trial (NCT04945772) enrolled 27 patients (ages 18+) with severe vision impairment due to RP.
The setup: Participants were randomized into three groups, with each group receiving one injection of either MCO-010 (two doses) or sham in the experimental arm:
- MCO-010 group (high dose: 1.2E11gc/eye)
- n = 9
- MCO-010 group (low dose: 0.9E11gc/eye)
- n = 9
- Sham comparator group
- n = 9
What was measured?
The primary outcome measure included efficacy of a single injection of MCO-010 as evaluated via best-corrected visual acuity (BCVA) using the Freiburg Visual Acuity (quantitative LogMAR) score, measured from baseline to week 52.
Secondary outcome measures were:
- Efficacy of MCO-010 via:
- BCVA at week 76, measured from baseline to week 76
- Change from baseline in mobility testing score (two methods)
- Static shape recognition assay (two methods)
- Change from baseline in visual field
Note: The timeframe for all secondary efficacy assessments (excluding BCVA) was the following: Weeks 16, 24, 32, 52, 76, and 100
Now this data.
Per Nanoscope, the study met its primary endpoint by demonstrating a statistically significant improvement in (BCVA) a week 52 in both dose groups of MCO-010 vs the sham group:
- High-dose (0.337 LogMAR; p=0.021)
- Low-dose (0.382 LogMAR; p=0.029)
Significance: the company noted that this randomized control trial (RCT) is the only one of its kind in retinal degenerative disease to “demonstrate improvement beyond the clinically important BCVA > 0.3 LogMAR threshold in a statistically significant manner.”
How much did visual function improve?
Improvements continued or increased after week 52 of the study period—indicating MCO-010’s “durable effect of a single intravitreal injection.”
Further, at week 76, the BCVA improvement was noted as statistically significant for the high-dose MCO-010 group vs the control group (0.539 LogMAR; p=0.001).
Was the same noted for the low-dose group?
At the same time point (week 76), a trend toward BCVA improvement was observed in the low-dose group, though it was not statistically significant vs the control group (0.374 LogMAR; p=0.065).
And how do these results compare to previous data on MCO-010?
Pretty consistent, according to Nanoscope.
See here for our coverage on the company’s key efficacy data reported from this trial in May 2023, and click here for positive topline data reported in April 2023.
And click here for positive data from a previous phase 1/2a open-label study on the optogenetic therapy, reported in June 2021.
Anything else?
Yes! Nanoscope also noted that—at week 52— a response rate of 89% in both MCO-010 groups was observed from the composite functional endpoint of novel, multi-luminance shape discrimination and y-mobility testing.
How about adverse events?
As with previous study results, no treatment-related serious or severe adverse events (AEs) were reported—the most common AEs were mild or moderate anterior chamber cell (ACC) reaction and ocular hypertension (OHT).
Expert input?
Per trial investigator David Boyer, MD, adjunct clinical professor of Ophthalmology at the University of Southern California Keck School of Medicine, significant vision restoration was observed in multiple patients with severe vision loss (including those who were completely blind).
"Many patients treated with MCO-010 derived a clinically meaningful benefit measurable on the primary visual function test,” he stated, “and this effect was confirmed by a parallel improvement in functional vision assessments.”
Nanoscope’s co-founder and CEO Sulagna Bhattachayra, PhD, also noted that the week 76 data “provide additional validation of Nanoscope’s versatile MCO platform, which is driving our expanding pipeline of programs in both Stargardt disease and [GA] due to [AMD].”
Significance?
With no currently-approved treatment, these latest data support MOC-010 as the potential first therapy for patients with advanced RP.
What’s next?
Based on RESTORE’s promising data, the company plans to submit a biologics license application (BLA) to the FDA in H2 (the second half of) 2024.
The eventual goal: to receive global regulatory commercialization for advanced RP.