information: Treatment of the first patient
Announcement: treatment of the first patient
Company: Adverum Biotechnologies (USA - CA)
- gene therapy. ADVM-043 (AAVrh.10-A1AT) is a gene therapy candidate that has the potential to induce stable, long-term A1AT protein following a single administration. In a preclinical proof-of-concept study, ADVM-043 demonstrated robust protein expression above therapeutic levels in mice following either IV or IP administration. In another study in non-human primates, evidence of stable long-term expression of hA1AT mRNA was observed out to one year following IP administration of ADVM-043.
- Alpha-1 antitrypsin (A1AT) deficiency is caused by mutations in the SERPINA1 gene, resulting in very low levels of A1AT. The current standard-of-care treatment for patients with A1AT deficiency with lung disease can be challenging, with weekly IV infusions of an alpha-1 proteinase inhibitor. The current treatment regimen can result in underdosing and lead to worsening lung function.
Disease: alpha-1 antitrypsin (A1AT) deficiency
area: Rare diseases - Genetic diseases
- The ADVANCE study is an open-label, multicenter, dose-escalation study in order to assess the safety and protein expression of ADVM-043 following intravenous or intrapleural administration in patients with A1AT deficiency. The study will include up to four dosing cohorts of up to 5 patients each. The first cohort will receive an intravenous (IV) low dose of ADVM-043 of 8E13 total vg (equivalent to approximately 1E12 vg/kg based on an 80-kg patient). The next two cohorts will receive an intermediate IV dose or high IV dose, with the fourth cohort potentially evaluating intrapleural (IP) delivery of ADVM-043.
- The primary endpoint is safety and tolerability and secondary endpoints include changes in plasma concentrations of both total and M-specific A1AT levels. Adverum expects to report preliminary data from this trial in the second half of 2018.
- • On December 28, 2017, Adverum Biotechnologies announced the dosing of the first patient in the ADVANCE Phase 1/2 clinical trial of ADVM-043 for alpha-1 antitrypsin (A1AT) deficiency. The ADVANCE clinical trial is designed to evaluate the safety and protein expression following a single administration of ADVM-043, Adverum’s novel gene therapy candidate. The study will include up to 20 patients across up to four dosing cohorts of up to 5 patients each. It will be conducted at 5 leading centers in the United States. The primary endpoint is safety and tolerability and secondary endpoints include changes in plasma concentrations of both total and M-specific A1AT levels. Adverum expects to report preliminary data from this trial in the second half of 2018.