BioMarin hemophilia gene therapy Phase III study was successful

Source: Medical Rubik's Cube Info January 10, BioMarin announced positive top-line results in a global Phase III study (GENEr8-1) on the treatment of severe type A haemophilia in the study of gene therapy valoctocogene roxaparvovec.
the study was the world's largest phase III gene therapy study to date, recruiting 134 subjects, all of them receiving a single dose of valoccogene roxaparvovec and completing a year or more of follow-up.
GenEr8-1 study had an average follow-up time of 71.6 weeks, and in 114 participants in non-interventional studies (subjects followed up for at least 6 months during group progression behavior to assess acceptance of preventive infusion FVI) The results of the analysis of annualized bleeding rate (ABR) at the main endpoint showed that single dose of valoccogene roxaparvovec significantly reduced ABR by up to 84%.
number of annual bleeding events in patients decreased from 4.8 previously collected (2.8) to 0.8 (medding 0.0) (p<0.0001), and 80% of the subjects no longer showed symptoms of bleeding after 5 weeks of treatment.
addition, valoctocogene roxaparvovec significantly reduced the subject's FVIII annual infusion rate by 99%.
number of FVIII infusions in patients decreased from 135.9 (medium 128.6) to 2.0 (medium 0.0) (p<0.0001).
1 year after receiving valoctocogene roxaparvovec treatment, the average endogenous FVIII expression level measured by the mITT population (n-132) using the color scheme (CS) was 43.6 (SD 45.3, with a medium value of 24.2) IU/dL, which supported a reduction in clinically observed bleeding and a decrease in FVI injection rates.
in 17 subjects who received valoctocogene roxaparvovec for at least 2 years, endogeneic FVIII expression levels increased from 42.2 (SD 50.9) at the end of the first year. The medium value of 23.9) IU/dL decreased to 24.4 (SD 29.2, medium value 14.7) IU/dL at the end of the second year, showing continuous hemostation, with an ABR of 0.9 (0.0).
Valoctocogene roxaparvovec was safe in all subjects and no FVIII inhibition or thromboembolism events occurred in patients.
one of the subjects was not interviewed.
reactions can be effectively reduced by controlling the speed of infusion.
most common adverse events (AEs) were elevated ALT, with an 86% (115 cases), and other common AEs included headache (51 cases, 38%), nausea (50 cases, 37%), AST elevation (47 cases, 35%), joint pain (38 cases, 28%) and fatigue (37 cases, 27%).
last August, the FDA rejected three years of phase III study data (26 weeks) and I/II study data provided by BioMarin, requiring it to provide two-year efficacy data for all subjects of Phase III studies.
is currently in communication with the FDA with a view to obtaining approval for valoctocogene roxaparvovec's treatment of severe haemophilia A.
, BioMarin plans to resubmit its MAA application to the EMA in the second quarter of 2021 after discussions with the EMA.
the FDA had previously awarded valoctocogene roxaparvovec breakthrough therapy to identify and treat orphans with severe haemophilia.
Valoctocogene roxaparvovec is a genetically modified gene therapy that uses AAV5 virus vectors to deliver expression coagulation factor VIII, with the advantage that it may take only one treatment to obtain a gene that expresses coagulation factor VIII, eliminating the need for long-term preventive coagulation factor injections.
'This is the first study to demonstrate the clinical superiority of gene therapy in reducing APR, and these data give us confidence in this breakthrough alternative therapy, pushing us one step closer to a potential new treatment option to meet the unsolved medical needs of patients with type A haemophilia,' said Dr. Steven W. Pipe, a professor of pediatrics and infectious diseases medicine at the University of Michigan's Department of Pathology.
data provide more scientific clinical evidence for the valoccogene roxaparvovec gene therapy for haemophilia type A and make it a potentially new treatment model for the disease.
is a recessive hereditary hemorrhagic disease with a chain of X chromosomes, which can be divided into haemophilia A and haemophilia B.
, haemophilia A is a lack of coagulation factor VIII. (FVIII.), accounting for about 80%-85% of all haemophilia patients, patients need life-long medication.
main clinical manifestations of frequent severe bleeding, more often in the joints, may lead to serious joint damage.
prevention treatment is the preferred treatment for patients with type A haemophilia, but patients need frequent intravenous treatment, and some patients receiving preventive treatment will still experience bleeding events.