A single infusion of FLT180a resulted in sustained mean Factor IX activity of 45%, with no toxicity or adverse effects, and eliminated need for patient infusions of FIX replacements
- Category: DNA RNA and Cells
- Published on Monday, 03 December 2018 09:25
- Hits: 27
December 3, 2018 I Freeline, a clinical stage gene therapy company focused on providing life-changing curative treatments for chronic diseases, on December 3rd presented initial results from the ongoing B-AMAZE Phase 1/2 trial investigating FLT180a for Haemophilia B. After one infusion, the two patients dosed in the lowest dose cohort achieved mean FIX activity levels of 45%±5, which approaches the normal range of 50-150%.
The presentation was made by UCL Professor Amit Nathwani, Chief Scientific Officer of Freeline, Director of the Katharine Dormandy Haemophilia Centre at the Royal Free Hospital and a Senior NIHR Investigator. The study was sponsored by University College London.
Two patients with severe Haemophilia B received FLT180a at a single dose of 4.5 x 1011 vector genomes/kg body weight. Enrolment criteria included FIX activity levels <2% and no neutralising antibodies to AAVS3, the company’s proprietary high performing liver specific capsid, as measured by a transduction inhibition assay. Within 4 weeks of infusion, FIX activity in both participants rose to greater than 30%, and at 15 weeks stabilised at 45% ±5%. This level has now been sustained for six and nine months, respectively.
FLT180a was well-tolerated in these patients, with no infusion related reactions or late toxicities, no evidence of transaminitis and no evidence of neutralising anti-FIX antibodies. Following gene transfer, there were no spontaneous bleeding episodes and no need for FIX concentrate usage.
Professor Amit Nathwani, Founder and Chief Scientific Officer of Freeline and Professor of Haemophilia at UCL Cancer Institute said:
“Every day, I meet with patients whose lives are severely disrupted by Haemophilia B and who aspire to live free of the effects of this disease. These clinical results show that the Freeline technology has the potential to provide these patients normalisation of FIX activity levels.”
Anne Prener, Chief Executive Officer of Freeline, added:
“Freeline has been built on the ambition of providing patients a gene therapy with high protein expression. I am excited about the results, which support escalation to the next dose level with the goal of developing a functional cure for people with Haemophilia B. These data provide initial validation in humans of our proprietary capsid and manufacturing platform and support our plan to quickly progress our broad pipeline of programmes in a variety of diseases.”