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Adverum Provides Update on ADVM-022 and the INFINITY Trial in Patients with Diabetic Macular Edema | ||
By: GlobeNewswire - 22 Jul 2021 | Back to overview list |
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-- Based on latest analyses, company is revising ADVM-022 development plan to focus on wet AMD and low doses (2 x 10^11 vg/eye and lower); no longer planning development for DME -- -- Company to host conference call and webcast today at 1:30 pm PT / 4:30 pm ET -- REDWOOD CITY, Calif., July 22, 2021 (GLOBE NEWSWIRE) -- Adverum Biotechnologies, Inc. (Nasdaq: ADVM), a clinical-stage gene therapy company targeting unmet medical needs in ocular and rare diseases, today provided an update on the ADVM-022 development program following a thorough review of data available from the INFINITY clinical trial in patients with diabetic macular edema (DME) and the OPTIC clinical trial in patients with wet age-related macular degeneration (wet AMD). The data from the studies show marked differences in the safety profile between the two patient populations and between the low (2 x 10^11 vg/eye) versus high (6 x 10^11 vg/eye) doses. Adverum no longer plans future development for DME after a dose-limiting toxicity (DLT) not seen before in ocular gene therapy or anti-VEGF treatment has been observed at the high dose (6 x 10^11 vg/eye) in patients with DME. The company is planning to evaluate ADVM-022, a single intravitreal (IVT) injection gene therapy, at low doses (2 x 10^11 vg/eye and lower) and with alternative prophylactic regimens in a future Phase 2 clinical trial in wet AMD. Wet AMD and DME have different pathophysiological causes with different risk factors. While the root cause of the DLT is not yet known, diabetic patients with DME typically have multiple underlying comorbidities, such as severe vascular disease, which can contribute to inflammatory factors that may induce an increase in vascular permeability and disrupt the blood-ocular barrier in DME patients.i As disclosed in late April 2021, Adverum immediately unmasked INFINITY and began closely monitoring all patients treated to date with ADVM-022 following a Suspected Unexpected Serious Adverse Reaction (SUSAR) of hypotony in the treated eye of a patient with DME who received a single high dose of ADVM-022. Additional patients in INFINITY treated with a single high dose of ADVM-022 have, despite close monitoring and aggressive treatment, experienced adverse events that have included rapid, clinically-relevant decreases in intraocular pressure refractory to steroids and requiring subsequent additional treatment. These events occurred 16-36 weeks after treatment with the high dose. No similar clinically-relevant events have been observed to date in DME patients in INFINITY treated with the low dose or to date in any wet AMD patients in OPTIC treated at either the high or low dose. The company is closely managing patient care working with the data monitoring committee (DMC), its scientific advisory board (SAB), leading retina specialists, and investigators. All clinical trial sites and the U.S. Food and Drug Administration (FDA) have been advised of these cases. “Our primary focus remains patient safety,” said Laurent Fischer, M.D., president and chief executive officer at Adverum Biotechnologies. “We deeply appreciate the continued expertise shared by the DMC, the SAB, retina specialists, and investigators to guide best patient care decisions. Gene therapy is a new and very promising, yet challenging field, as we work to develop durable treatments for patients. Our team is grateful for all of the patients and investigators participating in our clinical studies for their critical roles as we strive to shift the treatment paradigm through developing a one-time intravitreal gene therapy for patients.” Dr. Fischer continued, “Based on an ongoing, thorough review of the clinical and non-clinical data for ADVM-022, we are planning future development for wet AMD and we no longer plan to pursue DME. 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. Following completion of our analysis and discussions with advisors and regulators, we are planning a Phase 2 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.” “Working collectively, the DMC, SAB, investigators, leading specialists, and Adverum have taken swift action to assess and provide the best care to patients,” said Szilárd Kiss, M.D., Associate Professor in Ophthalmology and member of Adverum’s Scientific Advisory Board. “In unmasking INFINITY, the company has taken the right steps immediately to share findings real-time and ensure investigators can closely monitor patients and manage patient safety. Dose finding has been a challenge for the field of gene therapy, and while AAV remains a very safe delivery system, we should expect as with any biologic product that unexpected dose-limiting toxicities may be encountered. It is important to learn from the data generated by this field to bring new treatments with durable efficacy and well-managed safety to patients.” Long-term data from the OPTIC trial (n=30) of ADVM-022 for wet AMD have demonstrated long-term durability and maintained efficacy following a single, in-office IVT injection. Safety and efficacy data presented at the Association for Research in Vision and Ophthalmology (ARVO) in April 2021 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 (n=15). The company plans to present additional long-term data at a medical conference in the fall of 2021. The company plans to report financial results for the second quarter 2021 on August 5, 2021 after market close and remains well capitalized to execute on its priorities. Recent Developments
Anticipated Milestones for ADVM-022:
Conference Call Today About the OPTIC Trial of ADVM-022 in Wet AMD In Cohort 1 (n=6) and Cohort 4 (n=9), patients received a high dose (6 x 10^11 vg/eye) and in Cohort 2 (n=6) and Cohort 3 (n=9), patients received a low dose (2 x 10^11 vg/eye) of ADVM-022. Patients in Cohorts 3 and 4 received six weeks of prophylactic steroid eye drops rather than 13 days of prophylactic oral steroids which were used in Cohorts 1 and 2. The primary endpoint of the trial is the safety and tolerability of ADVM-022 after a single IVT administration. Secondary endpoints include changes in best-corrected visual acuity (BCVA), measurement of central retinal thickness (CRT) and the need for supplemental anti-VEGF injections. Each patient enrolled is being followed for a total of two years with the option to enroll in an extension study for an additional 3 years. For additional information about the OPTIC trial, please visit https://clinicaltrials.gov/ct2/show/NCT03748784 and for information about the long-term extension study, please visit https://clinicaltrials.gov/ct2/show/NCT04645212. About the INFINITY Trial of ADVM-022 in DME The INFINITY trial enrolled 36 patients and was designed to demonstrate superior control of disease activity following a single IVT injection of ADVM-022 compared to a single aflibercept injection, as measured by time to worsening of DME disease activity. Participants in this double-masked trial were randomized to one of three arms for their study eye treatment: Arm 1 received high dose (6 x 10^11 vg/eye) of ADVM-022, Arm 2 received low dose (2 x 10^11 vg/eye) of ADVM-022, and Arm 3 received aflibercept at a dose of 2 mg. Patients assigned to receive ADVM-022 were further randomized to receive either a preceding aflibercept or sham ocular injection. Additional objectives include assessments of treatment burden, visual acuity, retinal anatomy, and safety outcomes. For additional information about the INFINITY trial, please visit www.clinicaltrials.gov using Identifier NCT#04418427. About ADVM-022 Gene Therapy About Adverum Biotechnologies Forward-looking Statements ______________________ i Noma H, Mimura T, Yasuda K, Shimura M: Role of Inflammation in Diabetic Macular Edema. Ophthalmologica 2014;232:127-135. doi: 10.1159/000364955 CONTACT: Investor Inquiries Amy Figueroa, CFA Vice President, Investor Relations and Corporate Communications Adverum E: afigueroa@adverum.com T: 650- 649-1257 Media Inquiries Chantal Allan Sam Brown Inc. E: chantalallan@sambrown.com T: 805-242-3080 |
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