Nanoscope Therapeutics Inc. reported a “productive” end-of-phase 2 (EOP2) meeting with the FDA regarding its clinical program of Multi-Characteristic Opsin (MCO)-010 for the treatment of severe vision loss due to Stargardt macular degeneration (SMD; Stargardt disease [SD]).
First off, a company refresh.
The Dallas, Texas-headquartered biotechnology company is developing gene-agnostic, sight-restoring optogenetic therapeutics for inherited retinal diseases (IRDs).
Its investigational candidate pipeline: Gene therapies that deliver light-sensitive multi-characteristic opsins (MCOs), with the intent to treat the following IRDs:
- Dry age-related macular degeneration (AMD)
- Geographic atrophy (GA)
- Candidate: Optogenetics non-viral
- Geographic atrophy (GA)
- Cone rod dystrophy
- Retinitis pigmentosa (RP)
- Candidate: MC-010
- Most recently: Positive phase 2b trial data reported in March 2024
- Candidate: MC-010
- Stargardt disease (our topic of discussion)
- Candidate: MCO-010
- Usher syndrome
Now MCO-010.
As an ambient-light activatable MCO optogenetic agent, MCO-010 (sonpiretigene isteparvovec) is a gene therapy vector formulated to reprogram healthy retina cells—making them photosensitive—via a single intravitreal injection.
How it does this: 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.
- And the intended result: Potentially restoring vision with enhanced contrast and definition in real-world environments for patients with advanced RP.
How far into the clinical process is it?
To date, MCO-010 has received both FDA Orphan Drug and Fast Track designations for RP and SD.
- Also: The gene therapy is currently the only broadband, fast, and most-light-sensitive opsin in clinical trials.
As for trials: MCO-010 has been studied in the phase 2b RESTORE trial (NCT04945772) for RP—as well as a multicenter observational study for advanced RP (NCT05820100)—as well as the phase 2 STARLIGHT trial (NCT05417126) for SD.
Gotcha. So talk about the outcomes of this FDA meeting.
The company noted six key outcomes approved by the agency:
- Proposed phase 3 registrational trial design for SMD
- Design will include a single MCO-010 intravitreal dose group, randomized 1:1 to a sham-injection control cohort
- Primary efficacy endpoint
- Change in best-corrected visual acuity (BCVA) from baseline to Week 52
- Determined by testing on the Early Treatment Diabetic Retinopathy Severity (ETDR) chart
- Change in best-corrected visual acuity (BCVA) from baseline to Week 52
- Statistical methods for proposed primary / secondary endpoints
- These will inform further engagement with the FDA in order to align on statistical analyses
- Ongoing discussion / assistance for further evaluation in supporting the multi-luminance shape discrimination test as a key secondary endpoint
- Enrollment of legally blind patients with vision worse than 20/200 as well as patients as young as aged 12
- This is an extension of the patient population studied in the phase 2 trial
- Current nonclinical package sufficient to support a future Biologics License Application (BLA) submission
What else do we know about this phase 3 trial?
Nanoscope reports that the planned study will be the first randomized, controlled gene therapy for SD.
- The potential: To improve vision for patients with severe vision loss, including macular degeneration patients.
Note: No specifics were provided on when patient enrollment may commence.
Nice! With this in mind, what has previous clinical data shown?
Zeroing in on SD exclusively, we’ll refer to that phase 2b STARLIGHT trial (NCT05417126), which evaluated a single dose of virally carried MCO-010; dosed 1.2E11gc/eye) administered to six patients (≥16 years of age) diagnosed with SD, followed by 48 weeks of assessment.
The data: As we reported in August 2023, vMCO-010-treated patients demonstrated a clinically meaningful improvement in BCVA (a secondary outcome) and achieved an approximate 3 dB gain in mean sensitivity.
- The significance: This data supported MCO-010’s potential in becoming the first approved therapy for SD patients.
That definitely sound promising … and the company’s overall assessment?
Co-Founder and CEO Sulagna Bhattacharya noted that, following the positive topline data from the STARLIGHT trial, “the outcome of this meeting strengthens our conviction to advance clinical development of MCO-010 in this indication.”
They added: “We appreciate the FDA’s guidance and look forward to finalizing preparation for the phase 3 trial.”
And the eventual goal?
To receive global regulatory commercialization as the first approved therapy available to SD patients.