Shares of Adverum Biotechnologies plunged more than 20% in premarket trading after the company announced it was revising its clinical development plan for investigational gene therapy candidate ADVM-022 based on safety concerns in patients with diabetic macular edema (DME).
Shares of Adverum Biotechnologies plunged more than 20% in premarket trading after the company announced it was revising its clinical development plan for investigational gene therapy candidate ADVM-022 based on safety concerns in patients with diabetic macular edema (DME).
On Thursday, Redwood City, Calif.-based Adverum announced that a review of two separate studies assessing ADVM-022 revealed marked differences in safety for patient populations. Adverum has been studying ADVM-022 in DME as well as wet age-related macular degeneration (wet AMD). Adverum said data from the INFINITY study in DME raised concerns about safety, especially in the high doses of the medication. As a result, the company is suspending its study of ADVM-022 in DME. Specifically, Adverum cited toxicity concerns it had “not seen before in ocular gene therapy or anti-VEGF treatment” in patients with DME.
Concerns about the toxicity were first realized in April. At the time, Adverum unmasked the trial and closely monitored those DME patients who received the gene therapy after a patient who received the high dose was suspected of developing hypotony (low intraocular pressure) in the treated eye. Other patients who received the high dose experienced adverse events that have included rapid, clinically-relevant decreases in intraocular pressure, the company said. These events occurred 16-36 weeks after treatment with the high dose.
These events were not seen in the wet AMD study, Adverum said. The company now plans to evaluate a low dose of the gene therapy, along with alternative prophylactic regimens, in a Phase II clinical trial in wet AMD.
Laurent Fischer, M.D., president and chief executive officer at Adverum Biotechnologies, thanked the trial participants and researchers who assessed the gene therapy in DME after culling the program.
“The data show marked differences for ADVM-022 in patients with wet AMD versus DME. Our fully dedicated team and expert advisors are working relentlessly to better understand the root cause of the events experienced by certain high-dose patients in INFINITY and potential risk factors in these patients with DME,” Fischer said in a statement. “Following completion of our analysis and discussions with advisors and regulators, we are planning a Phase II clinical trial in wet AMD patients to explore additional low doses with alternative prophylactic regimens to support the best possible path for delivering ADVM-022 safely to patients.”
ADVM-022 is a gene therapy that harnesses Adverum’s propriety vector capsid, AAV.7m8. The therapy is delivered via a single intravitreal (IVT) injection and is designed to reduce the burden of frequent anti-VEGF injections and improve real-world vision outcomes for patients. ADVM-022 earned Fast Track Designation from the U.S. Food and Drug Administration for wet AMD.
The company noted that both wet AMD and DME have different pathophysiological causes with different risk factors. Although they have not determined the cause of the toxicity concerns in DME patients, Adverum noted that diseases have multiple underlying comorbidities, such as severe vascular disease. The vascular issues may have contributed to inflammatory factors that caused an increase in vascular permeability and disrupted the blood-ocular barrier in DME patients.
Long-term data from the wet AMD OPTIC study has shown ADVM-022 generated sustained durability and efficacy following a single dose. Data presented earlier this year showed 60% of patients were injection-free beyond one year and patients had an 85% reduction in annualized injection frequency following a single low dose, the company said. Additional long-term data will be presented later this year.
