UPDATE: Adverum's gene therapy reduces treatment burden in wet AMD, but questions remain

Adverum Biotechnologies' gene therapy for wet age-related macular degeneration (AMD) reduced treatment burden and maintained visual acuity in a phase 2 study, though a full picture can't be formed yet from the slice of early data.

The company's stock has fallen 18% to $2.28 compared to yesterday's market close price of $2.80 as of 10:45 a.m. ET today.

The data center around ixo-vec, an AAV-based gene therapy formerly known as ADVM-022 but renamed in 2022. Adverum had previously assessed the intravitreal injection in diabetic macular edema, an effort that was eventually discontinued after a patient went blind in the treated eye.

Now, interim ixo-vec data come from a phase 2 wet AMD study dubbed LUNA, with Adverum claiming the preliminary results demonstrate "potential best-in-class clinical activity in hard-to-treat patients including treatment burden reduction and maintenance of both visual acuity and anatomic endpoints."

The phase 2, double-masked trial is designed to evaluate the safety and efficacy of a single IVT injection of ADVM-022 at one of two doses, a high dose (2E11 vg/eye) and low dose (6E10 vg/eye), accompanied by one of four prophylactic corticosteroid treatment regimens designed to reduce anticipated inflammation that is associated with AAV-based gene therapy.

Among the 60 patients in the trial, no serious adverse events tied to the gene therapy were reported, according to Adverum. The biotech said ixo-vec was generally well tolerated, though specific safety data were not shared.

According to Adverum, the best performing prophylactic regimen appears to be a combination of Ozurdex and Durezol eye drops, with "the vast majority of patients" receiving the combo having no inflammation and over 90% of patients having minimal inflammation.  

On the efficacy side, the biotech reported maintenance of both visual acuity and anatomic endpoints that measures central subfield thickness (CST). In a sub-group analysis of patients with higher baseline CST, a greater CST reduction was seen, according to Adverum.

When looking at treatment burden reduction at 26 weeks, ixo-vec demonstrated annualized reduction in anti-vascular endothelial growth factor (anti-VEGF) injection rates of 90% among the 19 patients in the 6E10 cohort and 94% of the 20 patients in the 2E11 arm. At 26 weeks, ixo-vec demonstrated injection free rates of 68% for the 6E10 group and 85% of the patients in the 2E11 cohort.

"Our goal with Ixo-vec is to provide patients virtually injection-free management of their wet AMD lasting years and potentially for life," Adverum CEO Laurent Fischer, M.D., said in a Feb. 8 release, dubbing ixo-vec a "one-and-done" gene therapy on a call with Fierce Biotech. 

Mizuho analysts' "initial reaction" to the data was positive: "On first blush, we saw no serious adverse events, and with respect to efficacy, the data appear to be better than that recently reported from two wAMD gene therapy competitors over the past week."

The analyst firm is referring to data from competitor 4D Molecular Therapies and Regenxbio, both of which recently dropped respective phase 2 data in the indication.    

4DMT reported an 89% and 85% reduction in annualized anti-VEGF injection rates in its high (3E10 vg/eye) and low (1E10 vg/eye) dose arms for 4D-150, rates slightly lower than those seen for Adverum. Regenxbio’s AbbVie-partnered ABBV-RGX-314 demonstrated the highest reduction in treatment burden in more than 50 patients receiving the third dose level, with an 80% reduction in annualized injection rate.

Mizuho wasn’t quick to form a hard opinion, though, noting that “it may take time to fully digest the totality of this data set and others before we understand fully the efficacy and safety profile of ixo-vec and how it may stack up against its competitors.”

Adverum is expected to share a 26-week interim analysis from LUNA in mid-2024. The biotech anticipates engaging in official discussions with the FDA about phase 3 trial design after those results are shared, Fischer told Fierce, with a potential phase 3 launch slated for the first half of 2025.

Editor's note: This story was updated at 12:35 p.m. ET on Feb. 8 to include commentary from Adverum CEO Laurent Fischer.