The BBM-H901 injection independently developed by Shanghai Xinzhi Pharmaceutical Technology Co., Ltd. (an AAV gene therapy drug suitable for preventing bleeding in adult male patients with hemophilia B) has been approved for drug clinical trials by the National Medical Products Administration (NMPA) and will officially start registered clinical trials. This is the first hemophilia AAV gene therapy drug approved for registration in clinical trials in China, and also the first rare disease gene therapy administered systemically in China.
Zheng Jing, CEO of Faith Pharmaceuticals, said, "If small molecule drugs and antibody drugs are called the first two revolutions of biomedicine, gene therapy is seen as the third industrial revolution that will lead biomedicine. After years of technological accumulation, the market size of the gene therapy industry has grown rapidly, and large pharmaceutical companies such as Pfizer, Novartis, and Johnson&Johnson have laid out." Zheng Jing further stated, "Relying on a strong R&D team and core key technologies in the biotechnology field, Faith Pharmaceuticals is one of the few new startups in the global gene therapy new drug field that can compete with the technology of European and American multinational companies
BBM-H901 injection is an AAV gene therapy drug with independent intellectual property rights owned by Faith Pharmaceuticals. It introduces the human factor IX (FIX) gene into hemophilia B patients through intravenous administration, thereby increasing and maintaining the level of coagulation factors in the patient's body for a long time, in order to achieve a "one-time administration, long-term effectiveness" therapeutic and bleeding prevention effect. The design of BBM-H901 injection drug adopts a liver targeted serotype and efficient gene expression cassette with completely independent intellectual property rights, and uses the company's self-developed serum-free suspension culture and chromatography process for drug production that meets GMP requirements. BBM-H901 injection has the characteristics of good expression effect, high yield, and strong safety.
The gene therapy of BBM-H901 injection is one of the earliest AAV gene therapies to undergo clinical trials in China. Investigator Initiated Trial (IIT, NCT04135300) initiated by researchers began in 2019. Clinical research data shows that BBM-H901 injection has good safety and efficacy. After AAV gene therapy drug infusion, the levels of coagulation factors in patients' bodies significantly increase and remain stable for a long time. No significant adverse reactions were found during the clinical period, and the annualized bleeding rate (ABR) of patients was significantly reduced. In April 2021, Faith Pharmaceuticals officially submitted a clinical trial application (Investigational New Drug, IND) for BBM-H901 injection to the National Medical Products Administration (NMPA). On May 14, 2021, the Center for Drug Evaluation (CDE) officially accepted the application and approved BBM-H901 injection to enter the clinical trial phase on August 6, 2021.
In addition, according to CDE's recent announcement on August 9, 2021, the BBM-H901 injection from Xinzhi Pharmaceutical Technology has been approved for clinical use in hemophilia B.
Hemophilia B is a type of hemophilia caused by a lack of coagulation factor IX, accounting for approximately 15% of hemophilia cases. The most common treatment method is intravenous injection of concentrated factor IX, and severe hemophilia B patients will also receive preventive treatment to maintain coagulation factor IX. BBM-H901 is an AAV gene therapy that delivers the missing human coagulation factor (FIX) encoding gene to patients through a vector to increase endogenous FIX levels and treat hemophilia.
Although gene therapy has the potential to be a "once and for all" therapy, it is highly anticipated. However, the difficulty of successful development is enormous, and currently the most advanced gene therapies for hemophilia are not progressing smoothly. UniQure hemophilia B gene therapy AMT-061 has been reported as a potential safety event. At the end of last year (December 21, 2020), a phase III clinical trial of AMT-061 reported a case of hepatocellular carcinoma in a patient. Due to suspicion that the adverse event was related to AMT-061, the FDA suspended the clinical trial. On March 29, 2021, uniQure released a comprehensive investigation into the incident, which concluded that hepatocellular carcinoma is highly unlikely to be caused by eAMT-061. At present, there is no news of restarting clinical trials.
In addition to safety incidents, the durability of gene therapy efficacy for hemophilia is also a concern. Last August, the FDA refused to approve Roctavian, the first hemophilia A gene therapy to be declared for market. In the CRL, the FDA stated that BioMarin needs more data to support BLA and recommended that BioMarin complete the BMN 270-301 Phase III clinical study and provide 2-year follow-up data as substantial evidence that the therapy can sustain annual bleeding rate efficacy. On June 28th of this year, BioMarin once again submitted a Marketing Authorization Application (MAA) to EMA, despite Roctavian's recent disclosure of declining efficacy persistence.
Founded in September 2016, Faith Medicine (a subsidiary of Xinzhi Pharmaceutical Company) is a high-tech enterprise that integrates the research and development, production, and clinical application of gene therapy drugs. The company's founder is Professor Xiao Xiao, a well-known leader in the gene therapy industry. As a senior expert in the global gene therapy industry, Professor Xiao Xiao has over 35 years of experience in the development and transformation of AAV gene therapy industry, as well as profound international influence. He has led more than 20 domestic and international gene therapy research projects, successfully developed dozens of AAV gene therapy drugs and related key technologies, and his research results have been selected as one of the 100 major discoveries in the global scientific field of the year by the American magazine Discover.
Professor Xiao Xiao is also a well-known serial entrepreneur in the global gene therapy industry. In August 2016, its Bamboo Therapeutics company was acquired by Pfizer for $645 million, and the drug has now entered Phase III clinical trials; In October 2020, its founded Asklepios BioPharmaceutical company was acquired by Bayer for $4 billion, and multiple drugs have entered clinical stages.
Professor Xiao Xiao, founder of Faith Medicine
Faith Medicine has several globally leading patents and technologies, and has made comprehensive layouts in the fields of AAV novel capsids targeting different tissues, efficient transgenic expression cassette design, advanced clinical grade vector manufacturing processes, and innovative clinical development paradigms. It has successfully developed the world's leading HEK293 500L suspension culture process and large-scale downstream purification process using full chromatography. Multiple projects have entered the IND application and clinical validation stage. The company's R&D pipeline includes multiple indications such as hemophilia A, hemophilia B, Parkinson's disease, age-related macular degeneration, mucopolysaccharidosis, spinal muscular atrophy, etc.
The clinical trial approval of Faith Medicine's hemophilia gene therapy is not only a milestone event for the company, but also opens a new chapter in domestic AAV gene therapy. Relying on leading technology, Faith Medicine will continue to provide more effective and innovative solutions for monogenic genetic diseases, age-related diseases, and some malignant diseases through AAV (adeno-associated virus) vector technology. With technology as the foundation and patients as the concern, it will help promote public health.
