Adverum Biotechnologies have announced updates for three of its next-generation AAV-based therapy programs: ADVM-043, targeting alpha-1 antitrypsin (A1AT) deficiency, ADVM-022 targeting wet age-related macular degeneration (wAMD), and ADVM-053 targeting hereditary angioedema (HAE).
ADVM-043 is a single-administration treatment to potentially induce long-term A1AT protein expression. A1AT deficiency is an orphan disease which affects approximately 100,000 individuals in the United States, caused by mutations in the SERPINA1 gene, resulting in very low levels of A1AT, which is associated with developing emphysema and death. Adverum are currently treating A1AT deficient patients in the ADVANCE Phase I/II clinical trial. The first patient in Cohort 3 has been dosed with an escalated dose following a recommendation from the independent data monitoring committee (DMC), based on a review of the preliminary safety data from patients in Cohort 2. The trials primary endpoint is safety and tolerability, with secondary endpoints including changes in plasma concentrations of both total and M-specific A1AT levels. Adverum expects to report preliminary data from patients in Cohorts 1 through 3 by the end of this year.
Meanwhile, an Investigational New Drug application has been sent for ADVM-022 to initiate a Phase I trial. ADVM-022 is a gene therapy candidate for the treatment of (wAMD). Long-term preclinical data in a non-human primate model of wAMD was recently presented at the American Society of Gene & Cell Therapy in May 2018, showing that after 13 months a single intravitreal injection of ADVM-022 was found to be safe and statistically significant (p<0.0001) in the prevention of the development of Grade IV lesions compared to the vehicle control group. The results also demonstrated that ADVM-022 induced long-term efficacy that was comparable to aflibercept, an anti-Vascular Endothelial Growth Factor (VEGF) standard-of-care therapy, as the efficiacy at 13 months was found to be consistent with earlier reported data. Furthermore, the long-term preclinical data in the non-human primate model demonstrated ADVM-022 induced sustained intraocular expression of aflibercept for a period of up to 16 months following a single intravitreal injection.
Adverum also plans to submit an IND application to the FDA in the fourth quarter of 2018 for ADVM-053, a potential single-administration treatment for HAE, which is caused by a genetic mutation that results in low levels of the C1 esterase inhibitor (C1EI) protein, which is associated with sudden swelling and edema of respiratory airways, gastrointestinal tract, and extremities.
“We are excited to be able to share positive progress in our three lead gene therapy programs today and to share our continued commitment to improving the quality of life for patients with unmet medical needs,” commented Leone Patterson, interim president and chief executive officer of Adverum Biotechnologies.
Source: Adverum Biotechnologies Announces Clinical Progress Across Gene Therapy Pipeline