8-K: Adverum's Ixo-vec Shows Promising Results in Wet AMD Phase 2 Trial, 6E10 Dose Selected for Phase 3

Adverum Biotechnologies reports positive interim results from its LUNA Phase 2 trial of Ixo-vec for wet AMD, with the 6E10 dose demonstrating a potential best-in-class profile and selected for Phase 3 development.

Summary

• Adverum Biotechnologies announced interim efficacy and safety results from the LUNA Phase 2 trial of Ixoberogene soroparvovec (Ixo-vec) for wet age-related macular degeneration (AMD).
• The trial enrolled 60 patients, randomized equally across two dose cohorts: 6E10 and 2E11 vg/eye.
• The primary goal of the trial is to determine the optimal dose of Ixo-vec and corticosteroid prophylactic regimen for Phase 3 trials.
• The interim analysis, with a data cut-off of February 14, 2024, included 58 patients who completed the 26-week study visit.
• Both the 6E10 and 2E11 doses showed maintenance of visual and anatomic outcomes, with a significant proportion of patients remaining free of anti-VEGF injections.
• The 6E10 dose resulted in 76% of patients being injection-free, while the 2E11 dose had 83% injection-free patients at week 26.
• Mean annualized anti-VEGF injections were reduced by 90% in the 6E10 group and 95% in the 2E11 group.
• Visual acuity was maintained at both dose levels, with a least squares mean BCVA change from baseline of -1.1 letters for 6E10 and -2.2 letters for 2E11.
• Fluid control was also maintained, with a least squares mean central subfield thickness (CST) change from baseline of -12.6 μm for 6E10 and -12.0 μm for 2E11.
• Ixo-vec was well-tolerated at both doses, with no Ixo-vec-related serious adverse events reported.
• The most common Ixo-vec-related adverse events were mild to moderate anterior inflammation, responsive to local corticosteroids, and anterior pigmentary changes with no impact on vision.
• A patient preference survey showed that 88% of participants preferred Ixo-vec over their prior anti-VEGF treatments, and 93% would want to receive Ixo-vec in their other eye if they had bilateral disease.
• The 6E10 dose with local corticosteroid prophylaxis was selected for Phase 3 development.

Sentiment

Score: 8

Explanation: The document presents very positive clinical trial results, with strong efficacy and safety data, and high patient preference. The selection of the 6E10 dose for Phase 3 is a significant step forward. However, there are inherent risks in drug development, which temper the overall sentiment slightly.

Positives

• Ixo-vec demonstrated a significant reduction in the need for anti-VEGF injections, with a high percentage of patients remaining injection-free.
• Both doses of Ixo-vec maintained visual acuity and anatomic outcomes.
• The safety profile of Ixo-vec was favorable, with no serious adverse events related to the treatment.
• Enhanced corticosteroid prophylaxis improved the inflammatory profile compared to the OPTIC study.
• Patient preference for Ixo-vec over standard anti-VEGF injections was very high.
• The 6E10 dose with local prophylaxis was selected for Phase 3, indicating a clear path forward.
• 100% of patients receiving the 6E10 dose with difluprednate-alone prophylaxis had no or minimal inflammation at the 26-week timepoint and did not require additional corticosteroids.

Negatives

• A small percentage of patients experienced mild to moderate anterior inflammation, though this was responsive to local corticosteroids.
• Some patients in the Ozurdex + difluprednate prophylactic arm did not complete the scheduled regimen by the 26-week interim analysis data cut-off date, limiting full evaluation of this arm.
• Oral prednisone did not demonstrate incremental benefit in reducing inflammation.
• Ozurdex without difluprednate did not provide adequate prophylaxis.

Risks

• The company's novel technology makes it difficult to predict the timing of clinical trials.
• There are regulatory uncertainties associated with the development of new therapies.
• Enrollment uncertainties could impact the progress of clinical trials.
• Early clinical trial results may not always be predictive of future clinical trial outcomes.
• There is a potential for future complications or side effects in connection with the use of Ixo-vec.
• Cross-trial comparisons are inherently limited and may suggest misleading similarities or differences in outcomes.

Future Outlook

The company anticipates continued regulatory interactions with the FDA and EMA, presentation of the 9-month and 52-week LUNA trial data, a Phase 3 trial design update, and the planned initiation of a Phase 3 trial in the first half of 2025.

Management Comments

• Laurent Fischer, MD, President and Chief Executive Officer, highlighted the potential best-in-class profile for Ixo-vec at the 6E10 dose.
• Management emphasized the strong patient preference for Ixo-vec over standard of care anti-VEGF injections.

Industry Context

This announcement is significant in the context of the wet AMD treatment landscape, where there is a need for therapies that reduce the burden of frequent injections. The results suggest that Ixo-vec could be a competitive option, potentially offering a more durable treatment with a single injection.

Comparison to Industry Standards

• The document compares Ixo-vec's performance to other gene therapies for wet AMD, such as RGX-314 and 4D-150.
• Ixo-vec demonstrated a higher percentage of injection-free patients at 6 months compared to RGX-314 and 4D-150.
• Ixo-vec also showed a greater reduction in treatment burden at 6 months compared to RGX-314 and 4D-150.
• The OPTIC study, which used a higher dose of Ixo-vec (2E11), showed sustained aflibercept levels for up to 4.5 years, suggesting long-term durability.
• The LUNA trial's 6E10 dose demonstrated an improved safety profile compared to the 2E11 dose used in the OPTIC study, with a lower incidence of inflammation.

Stakeholder Impact

• Shareholders: The positive results and advancement to Phase 3 are likely to be viewed favorably by investors.
• Patients: The potential for a less burdensome treatment option with Ixo-vec is a significant benefit.
• Employees: The progress of the clinical trial is a positive development for the company and its employees.
• Healthcare providers: The data suggests a potential new treatment option for wet AMD.

Next Steps

• Continued formal and informal regulatory interactions with the FDA and EMA.
• Presentation of the landmark LUNA 9-month analysis in 4Q 2024.
• Update on the Phase 3 pivotal trial design in 4Q 2024.
• Presentation of the landmark LUNA 52-week analysis in 1Q 2025.
• Planned initiation of the Phase 3 trial in H1 2025.

Key Dates

Keywords

Ixo-vec, wet AMD, gene therapy, anti-VEGF, clinical trial, LUNA trial, ophthalmology, macular degeneration, aflibercept, corticosteroids