Breakthrough Clinical Results
Aldeyra Therapeutics announced that it received a Special Protocol Assessment Agreement from the FDA for ADX-2191, a novel formulation of methotrexate, for treating primary vitreoretinal lymphoma (PVRL). This follows a Complete Response Letter in 2023 requesting additional clinical trial data. The new protocol outlines a single clinical trial comparing cancer cell clearance in patients receiving either a single or multiple intraocular injections of ADX-2191. The trial is expected to begin in the second half of 2025 and conclude in 2026. ADX-2191 is a vitreous-compatible formulation designed for intraocular injection, potentially reducing injection volume compared to compounded methotrexate, the current standard of care for PVRL, a rare and potentially fatal cancer.
Key Highlights
- FDA grants Special Protocol Assessment for ADX-2191 in primary vitreoretinal lymphoma (PVRL).
- A single Phase 2 clinical trial will compare single vs. multiple injections of ADX-2191 for PVRL.
- Trial is expected to start in 2H 2025 and conclude in 2026.
- ADX-2191 is a novel, vitreous-compatible formulation of methotrexate designed for intraocular injection.
Incidence and Prevalence
Global Epidemiology of Primary Vitreoretinal Lymphoma
Based on the available information, there are no specific data on the global incidence and prevalence of Primary Vitreoretinal Lymphoma (PVRL) or intraocular lymphoma in the provided context.
The context explicitly states that after careful review, no information was found regarding: - Global epidemiological metrics - Incidence rates - Prevalence statistics
While there appears to be information in the original sources about diagnostic approaches, clinical manifestations, treatment options, and imaging findings related to vitreoretinal lymphoma, the context indicates that these sources focus on clinical features, diagnostic techniques, and treatment outcomes rather than population-based epidemiological metrics.
The context does not contain any information about geographical or demographic variations in PVRL incidence or prevalence patterns, as no epidemiological data was present in the reviewed materials.
Economic Burden
Economic Burden of Primary Vitreoretinal Lymphoma Treatment
After reviewing the available context, I cannot provide specific information about the economic burden of treating Primary Vitreoretinal Lymphoma (PVRL) in the USA and Europe. The context provided does not contain any data or studies related to:
- Economic costs associated with diagnosing and treating PVRL in the United States
- Financial burden metrics for management of PVRL across European healthcare systems
- Comparative economic analyses between US and European healthcare systems for PVRL treatment
- Cost-effectiveness analyses of different treatment modalities for PVRL
Without specific information from the context, I cannot provide the requested economic estimates or comparisons.
Study Design Parameters
Study Design Parameters and Endpoints in Primary Vitreoretinal Lymphoma Trials
Study Design Parameters
Primary Vitreoretinal Lymphoma (VRL) research has employed various study designs to investigate this rare condition. Retrospective reviews have been predominant, including a notable study examining 55 patients with vitreous specimens from the Mayo Clinic pathology database spanning 2000-2010. Similarly, a Korean retrospective analysis evaluated 20 patients diagnosed with intraocular lymphoma between December 2007 and June 2014.
Larger cohort studies included an analysis of 95 patients with vitreoretinal lymphoma to determine association with systemic lymphoma. For diagnostic purposes, a threshold study involving 119 patients (16 with VRL, 103 with uveitis) was conducted to establish IL-10 and IL-10/IL-6 ratio cutoffs.
Experimental approaches included a pilot study using biodegradable microneedle implants loaded with 10% methotrexate in albino New Zealand rabbits. For ongoing data collection, an International Vitreoretinal B-Cell Lymphoma Registry was designed to retrospectively gather information from individuals ≥18 years diagnosed with new or recurrent vitreoretinal B-cell lymphoma from January 2020.
Sample Collection Methods
Research protocols typically involved vitreous and serum samples collection. One study obtained samples from 14 patients with VRL and various controls (40 with uveitis, 12 with macular hole, 14 with epiretinal membrane, and 12 healthy individuals). Advanced molecular analysis included examining expression levels of 2565 miRNAs in these samples.
Vitreous aspiration biopsy was utilized for cytological confirmation of VRL. Additionally, aqueous humor (AH) and vitreous samples were collected specifically for IL-10 and IL-6 measurement, which serve as key diagnostic markers.
Key Endpoints
Diagnostic Markers
Studies established important diagnostic thresholds including IL-10 levels (cutoff of 65 pg/mL in vitreous, 30 pg/mL in AH) and IL-10/IL-6 ratio (>1 in vitreous). These markers demonstrated impressive sensitivity and specificity: IL-10 in vitreous (93% and 100%), IL-10 in AH (78% and 97%), and IL-10/IL-6 ratio >1 in vitreous (93% and 100%).
Survival Outcomes
The Korean study reported progression-free survival (PFS) with a median of 19.7 months (95% CI, 8.7-30.7 months) and overall survival (OS) with an estimated 3-year rate of 75.1%.
Biomarkers
Several miRNA biomarkers were identified, including miR-326 (associated with B-cell proliferation), miR-6513-3p (for discriminating VRL from uveitis), miR-1236-3p (showing correlation with IL-10), and miR-361-3p (serving as a discriminator between VRL and uveitis).
Additional Endpoints
Other important endpoints included histopathologic safety assessment of methotrexate implants in animal models, as well as visual outcomes and treatment response in retrospective studies.
International Registry Parameters
The International Registry collects 20 key clinical data items including patient demographics, tissue involvements, diagnostic testing, treatments, complications, visual acuity, and survival outcomes. Data is collected at 3-month reporting intervals. Planned outcome measures include descriptions of clinical presentations, diagnostic and therapeutic preferences, associations between presentations and treatments, and estimations of vision loss, progression-free and overall survival.
Drug used in other indications
ADX-2191 Clinical Indications Beyond Primary Vitreoretinal Lymphoma
Based on the available information, there is no specific data regarding ADX-2191 (methotrexate injection, USP) being trialed for indications other than Primary Vitreoretinal Lymphoma. The review of all relevant information does not reveal any additional clinical indications for which this specific formulation is being investigated.
Similarly, there is no information available about intervention models, study designs, or treatment protocols for clinical trials of ADX-2191 for indications beyond Primary Vitreoretinal Lymphoma.
The current data only confirms the investigation of ADX-2191 for Primary Vitreoretinal Lymphoma, without mention of additional therapeutic applications or specific trial methodologies for this particular formulation.