First hemophilia A patient dosed in trial of BBM-H803 in China

One-time gene therapy being developed by Belief BioMed to prevent bleeding

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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The first patient has been dosed in China in a registrational clinical trial of BBM-H803, a one-time investigational gene therapy that Belief BioMed is developing to prevent bleeding in hemophilia A.

The Phase 1/2/3 clinical trial (CTR20233400) is testing how safe and well tolerated BBM-H803 is as a single into-the-vein (intravenous) infusion for adults with severe hemophilia A. The company also plans to test how well it works over 52 weeks, or a year.

“Today is a special day for both Belief BioMed and hemophilia A patients, as the first patient dosing has been successfully completed in the registrational trial of BBM-H803,” Xiao Xiao, Belief BioMed’s co-founder, chairman, and chief science officer, said in a company press release. “This milestone means that Belief BioMed has made another major breakthrough in the field of gene therapy in hematological therapeutical area, and it once again confirms the company’s strong and robust research and development capabilities.”

Hemophilia A is caused by mutations in the F8 gene, which encodes a protein called factor VIII (FVIII) that’s needed for blood clotting. Without FVIII, people with hemophilia A may have excessive bleeding that can occur spontaneously or as a result of an injury or trauma.

BBM-H803, also called BBM-002, is made to deliver a working version of F8 to liver cells aboard a harmless adeno-associated virus (AAV) vector that acts as a delivery vehicle. Once the F8 gene is unloaded from the viral vector, liver cells can start producing FVIII. This is expected to increase FVIII levels for a long time, thereby helping to prevent bleeding.

No AAV-based gene therapies are available in China for treating hemophilia A so the company is “striving to bring this innovative gene therapy to the vast number of Chinese patients that need it as soon as possible,” Xiao said.

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Dosing begins in Phase 1/2a trial of optimized gene therapy for hem A

Recommended dose sought

A preliminary clinical trial of BBM-H803 where patient enrollment was completed last year backed the registrational clinical trial. The proposed clinical dose is lower than that of other AAV-based gene therapy options, which may reduce unwanted side effects, according to the company.

The registrational clinical trial plans to enroll up to 42 men with severe hemophilia A at eight clinical sites across China. The dose of BBM-H803 will be calculated according to each patient’s body weight.

Its main goal is to establish the therapy’s recommended dose during a dose escalation phase and to check on side effects, including changes to liver function, related to treatment with BBM-H803.

To test BBM-H803’s efficacy during a dose expansion phase, researchers will evaluate changes in the annualized bleeding rate, a measure of the number of bleeding episodes adjusted to a one-year window, over 52 weeks. Secondary measures include assessing FVIII activity levels.

BBM-H803’s safety is also being tested in an ongoing investigator-initiated Phase 1 clinical trial (NCT05454774) at the Institute of Hematology & Blood Diseases Hospital in Tianjin, China, where eight men with hemophilia A are expected to receive the gene therapy at a dose of 1×1013 vector genomes per kilogram of body weight (vg/kg).

In late 2022, the U.S. Food and Drug Administration granted BBM-H803 orphan drug status for hemophilia A. The designation provides a series of incentives, such as tax credits for clinical trials, exemption from user fees, and a potential seven-year period of market exclusivity should the therapy be approved.

Belief BioMed is also developing BBM-H901, an investigational gene therapy that’s under Phase 3 clinical testing for hemophilia B. Clinical data showed it was safe and helped prevent bleeds.