It’s been a big season for anyone with a vested interest in wet AMD, as advancement news for three different clinical studies was announced in September.
Wet (neovascular) age-related macular degeneration, or wet AMD, is a disease characterized by the loss of vision of the middle of the visual field caused by degeneration of the central portion of the retina (the macula). Abnormal growth of blood vessels below the retina, and the leakage of fluid and protein from the vessels, causes retinal degeneration that leads to severe and rapid loss of vision. Wet AMD is the leading cause of blindness in the developed world in individuals aged over 50 years, and its prevalence is increasing. Without treatment, wet AMD patients often experience a rapid decline in visual acuity.
The current standard-of-care therapy for wet AMD is anti-VEGF intravitreal injections. These are effective, but typically require long-term eye injections every four to eight weeks in order to maintain vision. Compliance with this regimen can be difficult for patients, caregivers and healthcare systems, leading to under-treatment and resulting in loss of vision.
The first piece of news addressing this condition comes out of Melbourne, Australia, where Opthea Limited announced new clinical data from a completed Phase 2b randomized controlled study of 366 patients using a combination of OPT-302 with ranibizumab (Lucentis) compared to ranibizumab alone. The data—originally presented at an international ophthalmology congress by Prof. Tim Jackson, chief investigator of the study and consultant ophthalmic surgeon at King’s College London—were presented again last month at the European Society of Retina Specialists EURETINA 2019 Congress in Paris.
Further analysis of the original findings of the study supports the initial outcome, which demonstrated superior vision gains following OPT-302 + ranibizumab combination therapy compared to the current standard therapy for wet AMD. OPT-302 combination therapy was also associated with improved anatomical changes of retinal lesions, including reduced central subfield thickness, and reduced subretinal fluid and intraretinal cysts. The combination therapy also led to reduced total lesion area and choroidal neovascularization area compared to ranibizumab alone.
“We are pleased to report additional results from our Phase 2b clinical trial at EURETINA. Together with the previously reported superiority in visual acuity gains, the further data analyses support the primary outcome of the study and demonstrate that OPT-302 has direct mechanistic effects on wet AMD lesion pathology,” commented Dr. Megan Baldwin, CEO and managing director of Opthea Ltd. “We continue to be encouraged by the positive outcomes of the further analyses of the Phase 2b trial. We anticipate reporting additional outcomes from the study over the following months at international ophthalmology meetings.”
Moving a bit earlier in the clinical timeline, Adverum Biotechnologies, Inc. had encouraging results to share regarding a Phase 1 trial. The company announced the presentation of positive 24-week clinical data from the first cohort of patients treated with a one-time intravitreal dose of ADVM-022 in the OPTIC Phase 1 clinical trial in wet AMD. Patients treated in this cohort achieved vision maintenance and improvements in retinal anatomy, with zero anti-VEGF rescue injections required, after a one-time intravitreal dose of ADVM-022 through week 24. In addition, ADVM-022 was found to be safe and well tolerated.
“Typically, patients with wet AMD require frequent anti-VEGF injections to maintain vision, representing a substantial treatment burden that often results in vision loss due to under-treatment. The single largest unmet clinical need for these patients is for a long-lasting anti-VEGF treatment,” explained Dr. Szilárd Kiss, a retinal specialist who presented the data at the Retina Society 2019 Annual Meeting in London in September. “These data on ADVM-022 are compelling, as they demonstrate for the first time that a one-time gene therapy delivered by intravitreal injection has the potential to provide sustained efficacy and transform the treatment paradigm for patients with wet AMD.”
Aaron Osborne, chief medical officer of Adverum, added, “Given these positive results from OPTIC, we are working with key stakeholders to continue development and seek regulatory approval of ADVM-022 to meet our goal of delivering this novel gene therapy candidate as soon as possible to patients with wet AMD and diabetic retinopathy, our second indication for ADVM-022. I’d like to thank the investigators, patients and caregivers for their ongoing participation in the OPTIC trial.”
Going forward, an update on further development plans for the OPTIC trial will be provided in the fourth quarter of 2019 with 52-week data from the first cohort of patients, with 24-week data from the second cohort of patients in the OPTIC trial to be presented in the first half of 2020. Adverum expects to be able to occupy its new corporate headquarters in Redwood City, Calif., by the end of this year, allowing for the expansion of in-house process development capabilities to the 1000-liter production scale, and the company is planning the submission of an Investigational New Drug application for ADVM-022 in diabetic retinopathy in the first half of 2020.
And for the third study, this one at the far end of the clinical track, Outlook Therapeutics Inc. announced in August that it had completed patient enrollment for the NORSE 1 Phase 3 clinical trial, which is evaluating ONS-5010 against ranibizumab for wet AMD. A total of 61 patients at nine sites in Australia will participate in the first of two ongoing, adequate and well-controlled Phase 3 clinical trials evaluating ONS-5010 against ranibizumab for wet AMD. The study will look for a mean change in baseline visual acuity at 11 months for ONS-5010 dosed on a monthly basis, compared to ranibizumab dosed using the PIER alternative dosing regimen of three monthly doses followed by quarterly dosing. Outlook expects to announce a readout of the top-line results from NORSE 1 in the third quarter of 2020.
If this clinical program is successful, Outlook will submit for regulatory approval in multiple markets in 2020. Once approved, ONS-5010 has potential to mitigate risks associated with off-label use of Avastin or other drugs, which is currently estimated to account for at least 50 percent of all wet AMD prescriptions in the United States for Avastin alone.
“We are pleased with the building momentum in our two ongoing Phase 3 clinical trials for ONS-5010, including completing enrollment in NORSE 1. Achieving this milestone keeps us on track for our goal to submit ONS-5010 for regulatory approval in the United States in 2020, pending the successful outcome of our trials. I am very proud of our clinical development team’s work as we move this program forward in an effort to provide an approved bevacizumab treatment option for wet AMD patients around the world,” said Lawrence A. Kenyon, president, CEO and chief financial officer.