Molecule of DNA forming inside the test tube equipment.3d rendering,conceptual image.
Molecule of DNA forming inside the test tube equipment. [undefined/Getty Images]

Belief BioMed’s BBM-H901, the first intravenously injectable hemophilia B gene therapy product developed and tested in Asia, showed very promising results in a Phase I study. Findings suggest that BBM-H901 is safe one year after infusion. Factor IX coagulation (FIX:C) concentration was sufficient to prevent bleeding events and minimize the need for replacement therapy in subjects.

The trial results are published in The Lancet Haematology, with Feng Xue, MD, of China’s National Clinical Research Center for blood diseases, as the lead author. The trial was sponsored by the Institute of Hematology and Blood Diseases Hospital at the Chinese Academy of Medical Sciences in collaboration with biotech Belief BioMed and East China University of Science and Technology.

As the authors write “The safety and long-term efficacy of this treatment strategy have been demonstrated with significant relief of disease symptoms.”

BBM-H901 is molecularly engineered adeno-associated virus (AAV) based gene therapy drug for hemophilia B. Belief BioMed has the proprietary rights of the AAV capsid and the expression cassette. The company reports that the novel human liver-tropic AAV capsid can efficiently infect liver cells, greatly shorten the circulation time of drugs in the blood, and reduce the immune response generated by the capsid.

The product’s novel expression cassette uses a mini-liver-specific promoter to drive expression of FIX-padua. The company reports it has achieved several proprietary improvements in process and quality control, forming an advanced, reliable, efficient chemistry, manufacturing, and control process, with a single production cell culture volume of up to 500L currently.

The study included 10 patients with moderate to severe hemophilia B (FIX:C<2%) who were intravenously infused with 5×1012vg/kg BBM-H901. A median follow-up of 58 weeks was completed, and the factor IX coagulation factor reached the mean 36.9±20.5IU/dl. Compared with similar international studies, BBM-H901 appears to work rapidly with vector-derived FIX:C expression within 24h following gene therapy.

Among study subjects, median annualized bleeding rate decreased from 12 times to 0, the median number of target joints decreased from 1.5 to 0, and the median number of FIX infusions decreased from 53.5 times to 0. In addition, BBM-H901 also demonstrated a good safety profile, with no Grade 3–4 adverse events reported over the follow-up period.

“The study was the first clinical trial conducted by Belief BioMed in China. We are very grateful to our partners for their great support throughout the journey,” said Jane Zheng, CEO of Belief BioMed. “We are very proud to introduce BBM-H901, which is the first intravenously delivered gene therapy drug for hemophilia B in China and the first example of systemic gene therapy for rare diseases in China. We will continue to advance discovery and research of all other pipelines, and to accelerate clinical trials and commercialization of the drugs. We hope gene therapy could be accessible to patients with rare or common diseases as soon as possible.”

Zhang Lei, Professor and Vice Director of Institute of Hematology and Blood Diseases Hospital at the Chinese Academy of Medical Sciences said, “The BBM-H901 study is the first clinical study in China and even Asia to utilize liver-targeted AAV vectors for the treatment of hemophilia B.”

Also of Interest