Clinical trials: Companies tackle AMD in early 2024

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Age-related macular degeneration (AMD) is among the leading causes of vision loss. For this reason, many companies see the importance of developing treatment options that would allow patients to preserve or potentially regain some visual acuity. As the pipeline of pharmaceuticals fills with more and more candidates, we look back on the first quarter of 2024, to highlight some of the key players in the space and the data that supports the treatments they are developing.

Note: The following updates are provided in alphabetical order by company name and are a non-exhaustive list of current AMD trials.

4DMT

In January, 4D Molecular Therapeutics announced that the FDA granted the RMAT designation for the investigational genetic medicine candidate 4D-150 for intravitreal treatment of wet AMD. The company noted the designation comes on the heels of interim Phase 1 PRISM clinical data for 4D-150 that demonstrated an encouraging safety, tolerability, and clinical activity profile.

In February, the company announced positive interim data from the Phase 2 PRISM clinical trial evaluating intravitreal 4D-150, which met a favorable safety profile with no significant or recurring intraocular inflammation. 4D-150 also reduced treatment burden while effectively controlling disease activity without fluid fluctuations.

4DMT noted that additional FDA and EMA interactions planned in Q2 2024, with an update expected in Q3 2024.

Adverum

At the 47th annual meeting of the Macula Society, Arshad Khanani, MD, MA, FASRS, presented preliminary safety and efficacy data on the ongoing LUNA Phase 2 trial in patients with wet AMD from Adverum Biotechnologies Inc. The LUNA Phase 2 trial evaluated Ixoberogene soroparvovec (Ixo-vec) intravitreal gene therapy in 60 patients with wet AMD were enrolled equally across two dose cohorts, 2E11 and 6E10 vg/eye.

Ixo-vec was generally well-tolerated, and when present intraocular inflammation was responsive to local corticosteroids. No Ixo-vec related serious adverse events were reported. Both the 2E11 and 6E10 doses demonstrated maintenance of visual and anatomic outcomes.

Read Modern Retina’s coverage for further data points.

Alvotech

In January, Alvotech announced positive top-line results from a confirmatory clinical study for AVT06, Alvotech’s proposed biosimilar to aflibercept. The company is focusing on biosimilars and sees AVT06 as a key clinical milestone.

AVT06-GL-C01 confirmatory clinical study is a randomized, double-masked, parallel-group, multicenter, therapeutic equivalence study evaluating the efficacy, safety, and immunogenicity of AVT06 compared with aflibercept (Eylea) in patients with wet AMD. The primary outcome measure was change from baseline to Week 8 in Best-Corrected Visual Acuity (BCVA). The study met its primary endpoint, with results demonstrating therapeutic equivalence between Alvotech’s biosimilar candidate and Eylea.

Bayer AG and Regeneron

In early January of 2024, the European Commission granted marketing authorization for aflibercept (Eylea) 8mg. Approval was recommended based on results from the PULSAR and PHOTON randomized, double-masked, active-controlled pivotal trials. The data from these trials indicated an extended period between dosing with 8 mg aflibercept, compared to 2 mg aflibercept, could significantly lower patient burden.

The PULSAR study was a randomized study, patients with neovascular AMD were assigned to 1 of 3 treatment groups, i.e., aflibercept 2 mg every 8 weeks, aflibercept 8 mg every 12 weeks, or aflibercept 8 mg every 16 weeks after 3 initial monthly doses. The primary efficacy endpoint was the mean change in BCVA from baseline at week 48. The results showed that at weeks 48 and 96, the 2 groups treated with aflibercept 8 mg demonstrated non-inferior BCVA gains compared to aflibercept 2 mg administered every 8 weeks. The non-inferiority P values at week 96 for aflibercept 8mg every 12 and 16 weeks were 0.0006 (nominal) and 0.0007 (nominal), respectively. The investigators found no new ocular safety signals for aflibercept 8 mg compared with aflibercept 2 mg.

Cognition Therapeutics

In a 2024 update, Cognition Therapeutics CEO, Lisa Ricciardi, noted that the company was actively enrolling participants in the 246-patient Phase 2 MAGNIFY study for adults with dry AMD who have measurable geographic atrophy. This trial will evaluate whether CT1812, a small molecule, oral medication capable of crossing the blood-retinal barrier and shown to reach the back of the retina without an injection, has a beneficial effect on the retinal damage-response processes.

EyePoint Pharmaceuticals

EYP-1901 is a pan–VEGF receptor inhibitor from EyePoint Pharmaceuticals. In the DAVIO-2 trial, EYP-1901 was compared with aflibercept. After 3 loading doses, the patients were randomly assigned to receive EYP-1901 or continue to receive aflibercept at an 8-week dosing pattern for 32 weeks. The study is set for 56 weeks overall, meaning there will be a long-term outcome from the study as well. Modern Retina reviewed the data of this study with Rishi P. Singh, MD, as well as Carl D. Regillo, MD, FACS, FASRS.

Ocular Therapeutix

In February, Ocular Therapeutix Inc. screened the first 3 subjects in the Phase 3 SOL-1 clinical trial of AXPAXLI (axitinib intravitreal implant, also known as OTX-TKI) for the treatment of wet age-related macular degeneration (wet AMD). These 3 participants have also received their first aflibercept injection. AXPAXLI is an investigational bioresorbable, hydrogel implant incorporating axitinib, a small molecule, multi-target, tyrosine kinase inhibitor with anti-angiogenic properties, being evaluated for the treatment of wet AMD and other retinal diseases.

Outlook Therapeutics

The European Medicines Agency (EMA) has issued a positive Committee for Medicinal Products for Human Use (CHMP) opinion concerning the authorization of bevacizumab gamma (ONS-5010/LYTENAVA), a formulation of bevacizumab for treatment of wet age-related macular degeneration (wet AMD). The European Commission is expected to make a decision about the application before the end of June.

REGENXBIO

AAVIATE is a Phase II, multi-center, open-label, randomized, active-controlled, dose-escalation trial that is evaluating the efficacy, safety and tolerability of suprachoroidal delivery of ABBV-RGX-314, a gene therapy treatment, in patients with wet AMD.

According to the REGENXBIO news release regarding the positive interim data, the primary endpoint of the trial is mean change in vision in patients dosed with ABBV-RGX-314, as measured by best corrected visual acuity (BCVA) at Week 40 from baseline, compared to patients receiving monthly injections of ranibizumab. ABBV-RGX-314 continues to be well tolerated in over 100 patients from 3 dose levels with no drug-related serious adverse events. ABBV-RGX-314 in over 50 patients at third dose level demonstrated highest reduction in treatment burden. Zero cases of intraocular inflammation observed in patients that received short-course prophylactic topical steroid eye drops.

Further reading

As patients with AMD continue to present to ophthalmologists for treatment, some providers may seek clinical trial enrollment for their patients. In a Modern Retina’s Spring 2024 issue, Pamela Ann Weber, MD, shares her insights as to which patients are right for clinical trials and how providers can become a part the meaningful work of clinical trials.

Read the article