Aldeyra Therapeutics announced positive topline data from the phase 2 trial on its investigational drug candidate ADX-2191 (intravitreal methotrexate 0.8%) for the treatment of retinitis pigmentosa (RP).
Give me a quick refresh on this drug.
ADX-2191 is a preservative-free intravitreal formulation of methotrexate that is being assessed for the potential prevention or treatment of specific rare retinal diseases such as primary vitreoretinal lymphoma (PVRL), proliferative vitreoretinopathy (PVR), and retinitis pigmentosa (RP).
The therapeutic is the first sterile, non-compounded formulation of methotrexate designed for intravitreal administration for specific rare retinal diseases.
To note, the FDA has already granted ADX-2191 orphan drug designation (ODD) for the treatment of PVR and RP.
Wait … didn’t we just hear about it?
Yup we did! The FDA determined last week that ADX-2191’s new drug application (NDA) submission for PVRL lacked substantial evidence of effectiveness.
This followed the agency granting the drug candidate priority review in March 2023.
Is there a connection to these new results?
Not really. The NDA submission was for ADX-2191 in treating PVRL; this latest data is on the use of ADX-2191 for treating RP.
Gotcha. What should I know about this study?
According to Aldeyra, the study design was based on preclinical evidence that methotrexate may facilitate clearance of mutated rhodopsin (a protein essential for visual cycle function).
And the actual study?
The open-label, non-randomized, single-center phase 2 clinical trial (NCT05392179) enrolled eight patients diagnosed with RP due to rhodopsin mutations (including P23H) in order to assess the use of repeated ADX-2191 injection in the worst seeing eye.
How about the dosages?
Patients were randomized to receive monthly injections (n = 4) or twice-monthly injections (n = 4) of ADX-2191 (400 µg in 0.05 mL).
What was measured?
The primary outcome measure was the safety of ADX-2191, measured by the incidence of adverse events (AEs) among the patients.
Secondary endpoints included a change in:
- Visual acuity (from baseline)
- Retinal function
- Retinal morphology
- Central subfield foveal thickness and ellipsoid zone area/width
How and when?
Retinal function was assessed via macular and dark-adapted chromatic perimetry and electroretinography (ERG), while retinal morphology was evaluated via optical coherence tomography (OCT).
All assessments were performed over a 4-month period after the first injection. ERG took place at baseline and at 90 days following the first injection.
And the findings?
All patients completed the study, with a statistical significance being achieved for improvement in:
- Best-corrected visual acuity (BCVA) (P<0.0001)
- Low-light visual acuity (P=0.0001)
- ERG response time to light (P=0.02)
- Macular sensitivity to light (P<0.0001)
- Dark-adapted peripheral sensitivity to light (P<0.0001)
Any safety concerns?
Nope! ADX-2191 was also found to be well-tolerated, with no treatment-related AEs associated with retinal morphology or any AEs observed.
So what’s next?
According to Aldeyra, the company intends to discuss a planned phase 2/3 trial with the FDA.