The IIT is a single-arm, open-label, single-dose administration clinical trial to evaluate the safety and tolerability of GS1191 in HA patients older than 18 years of age whose endogenous factor VIII (FVIII) activity was lower than 1 IU/dL (<1%). 12 patients with HA were enrolled in two dose groups (6 in the 2E12 vg/kg group and 6 in the 4E12 vg/kg group, respectively). The last patient was enrolled on May 17, 2023, and all the enrolled patients have been followed up for at least 12 weeks after dosing by Aug. 9, 2023. Preliminary results indicate that GS1191 can continuously and significantly improve the endogenous FVIII activity. All the enrolled patients have experienced significant reductions in Annualized Bleeding Rate (ABR) after receiving GS1191 infusions. Currently, all patients enrolled in 4E12 vg/kg dose group have normal FVIII activities with no episodes of bleeding events observed after dosing. Most of the adverse events (AEs) reported in this IIT study were grade 1 in severity. No AEs have been observed in any patients receiving either dose considered to be grade 3 or higher in severity, indicating a favorable safety profile.
GS1191 received clinical trial approval from the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) in January of this year. The IND approval was granted by NMPA in January 2023. This multicenter, single-arm, open-label, single-dose administration Phase 1 study was designed to evaluate the safety, preliminary efficacy, and vector kinetics profile of a single intravenous infusion of GS1191 at different dose levels in patients with severe HA and determine the dose for Phase 2/3 clinical studies based on the patients’ benefit/risk profile. The first patient has been dosed in the China Phase 1 trial on Aug. 2, 2023.
Dr. Wu Fenglan, Co-founder and CEO of Gritgen, commented that, "as the first flagship gene therapy product developed independently by our company, Gritgen's GS1191 has successfully achieved First Patient In Phase I and all the enrollment in the IIT study. We appreciate the investigators, patients and their families as well as our own team, for bringing effective and valuable treatment to HA patients."
GS1191 is the first gene therapy product for HA gaining IND approval in China. Dr. Wu Fenglan further remarked that, "the outstanding safety and efficacy data from IIT have instilled immense confidence in the entire team. Gritgen is committed to developing innovative gene therapy products, revolutionizing the quality of life of patients at the genetic level, and reshaping the clinical treatment pattern of hemophilia A."
About Hemophilia
Hemophilia is an X-linked recessive hereditary bleeding disorder. Epidemiology estimates approximately 120,000 patients with hemophilia in China. This disorder can be classified into Hemophilia A (HA) and Hemophilia B (HB). HA accounts for about 85% of all hemophilia patients, making it the most prevalent subtype. HA results from mutations in the gene encoding FVIII, causing a genetic deficiency of coagulation factor VIII. HB, constitutes about 15% of all hemophilia cases and is caused by mutations in the F9 gene, resulting in an genetic deficiency of coagulation Factor IX. Factor VIII is larger than factor IX, making it the more difficult to be delivered by gene therapy. The success of delivering Factor VIII means that technically, the same team should be able to deliver Factor IX.
The primary manifestations of hemophilia are spontaneous bleeding or excessive bleeding following minor injuries. The standard clinical treatment for hemophilia involves replacement therapy with coagulation factors, requiring lifelong injection of proteins on a regular basis, which brings a significant economic burden to patients, their families, and societies. Gene therapy stands as a cutting-edge technology with the potential to offer a cure for hemophilia patients with a single injection.
About GS1191-0445 Injection
GS1191 is an investigational adeno-associated virus (AAV) gene therapy for the treatment of Hemophilia A. GS1191 can deliver human FVIII gene to patients with Hemophilia A in vivo and achieve long-term gene expression via a single dose of intravenous infusion, thereby raising and sustaining endogenous FVIII activity over the long term. As an innovative treatment, the goal is to achieve a therapeutic effect of "single-dose, long-term efficacy" by addressing the underlying cause and preventing bleeding events.
GS1191 is the first gene therapy product receiving IND approval from NMPA in January 2023, and the first product completing patient enrollment for IIT in China.
About Gritgen
Founded in 2019 by Dr. Yi Rao, a leader of biomedical research in China, Gritgen is dedicated to apply “Great Science for Human Health”. The company has independently developed a globally leading highly efficient GritPAC and GritOcul platform. Combining fundamental understanding of genetics and biology of diseases with modern technologies in molecular biology, Gritgen has developed multiple product pipelines in rare and common diseases to fulfill the unmet medical needs of patients and improve the health of people in China and the world.
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