Full Press Release Details
SAN RAFAEL, Calif. , Feb. 4, 2022 /PRNewswire/ -- BioMarin Pharmaceutical Inc. (NASDAQ: BMRN ) today announced that the Company presented positive results from a two-year analysis of the Phase 3 GENEr8-1 study and an overall safety update of valoctocogene roxaparvovec, an investigational gene therapy for the treatment of adults with severe hemophilia A, at the 15 th Annual Virtual Congress of the European Association for Haemophilia and Allied Disorders (EAHAD). This is the largest global Phase 3 study to date for any gene therapy in hemophilia with 134 participants.
In the GENEr8-1 Phase 3 study, Annualized Bleeding Rate (ABR) was significantly reduced by 4.1 treated bleeds per year (p-value <0.0001), or by 85% from a baseline mean of 4.8 (median 2.8), in the pre-specified primary analysis in participants from a prior non-interventional study (rollover population; N=112; median follow-up of 110 weeks). The percentage of participants with zero treated bleeds increased from 32% on prophylaxis at baseline to 82% during year 1 and 84% during year 2. The mean ABR was 0.8 (median 0.0) through the entire efficacy evaluation period, 0.9 (median 0.0) during year one, and 0.7 (median 0.0) during year two.
Across all participants in the rollover population (N=112), mean annualized Factor VIII infusion rate was reduced by 133 infusions per year (p-value <0.0001) or 98% from baseline. As of the two-year data cut, 95% of participants remain off Factor VIII prophylactic therapy.
"This data demonstrates sustained bleed control is possible at the lower limits of quantification of Factor VIII activity, which may be the start of understanding the durability of gene therapy in hemophilia A, particularly with valoctocogene roxaparvovec," said Prof. Johnny Mahlangu , a study investigator and Professor in Haematology and Head of School of Pathology in the Faculty of Health Sciences of the University of the Witwatersrand in Johannesburg , South Africa. "I am pleased to see that a high level of study participants remains off prophylaxis reducing the burden of injecting themselves over a hundred times a year."
"We are pleased to share these transformational data at EAHAD that show this important advance for more than 80% of study participants, who are bleed free and more than 95%, who do not require Factor VIII prophylactic therapy," said Hank Fuchs , M.D., President of Worldwide Research and Development at BioMarin. "Such outcomes are not afforded by any currently available therapy."
Valoctocogene Roxaparvovec Safety
All participants in the Phase 3 study received a single 6e13 vg/kg dose. No participants developed inhibitors to Factor VIII, malignancy, or thromboembolic events. During year two, no new safety signals emerged, and no treatment-related serious adverse events (SAE) were reported. Most patients had discontinued any corticosteroid (CS) use in year one, and there were no CS-related SAEs in the remaining patients being tapered off CS in year two. Overall, the most common adverse events (AE) associated with valoctocogene roxaparvovec occurred early and included transient infusion associated reactions and mild to moderate rise in liver enzymes with no long-lasting clinical sequelae. Alanine aminotransferase (ALT) elevation (119 participants, 89%), a laboratory test of liver function, remained the most common AE. Other common adverse events were headache (55 participants, 41%), arthralgia (53 participants, 40%), nausea (51 participants, 38%), aspartate aminotransferase (AST) elevation (47 participants, 35%), and fatigue (40 participants, 30%). In a Phase 1/2 study, an SAE of a salivary gland mass was identified in one study participant, who was treated more than five years ago, and was reported as unrelated to valoctocogene roxaparvovec by the investigator. The relevant health authorities were notified in late 2021, and all studies remain ongoing without modification. The independent Data Monitoring Committee (DMC) further reviewed the case. A genomic analysis is being conducted as prespecified in the clinical trial protocol.
GENEr8-1 Study Description
The global Phase 3 GENEr8-1 study evaluates superiority of valoctocogene roxaparvovec at the 6e13 vg/kg dose compared to the current standard of care, FVIII prophylactic therapy. All study participants had severe hemophilia A at baseline, defined as less than or equal to 1 IU/dL of Factor VIII activity. The study included 134 total participants, all of whom had a minimum of 24 months of follow-up at the time of the data cut. The first 22 participants were directly enrolled into the Phase 3 study, 17 of whom were HIV-negative and dosed at least 36 months or 3 years prior to the data cut date. The remaining 112 participants (rollover population) completed at least six months in a separate non-interventional study to prospectively assess bleeding episodes, Factor VIII use, and health-related quality of life while receiving Factor VIII prophylaxis prior to rolling over to receive a single infusion of valoctocogene roxaparvovec in the GENEr8-1 study.
About Hemophilia A
People living with hemophilia A lack sufficient functioning Factor VIII protein to help their blood clot and are at risk for painful and/or potentially life-threatening bleeds from even modest injuries. Additionally, people with the most severe form of hemophilia A (FVIII levels <1%) often experience painful, spontaneous bleeds into their muscles or joints. Individuals with the most severe form of hemophilia A make up approximately 50 percent of the hemophilia A population. People with hemophilia A with moderate (FVIII 1-5%) or mild (FVIII 5-40%) disease show a much-reduced propensity to bleed. The standard of care for individuals with severe hemophilia A is a prophylactic regimen of replacement Factor VIII infusions administered intravenously up to two to three times per week or 100 to 150 infusions per year. Despite these regimens, many people continue to experience breakthrough bleeds, resulting in progressive and debilitating joint damage, which can have a major impact on their quality of life.
Hemophilia A, also called Factor VIII deficiency or classic hemophilia, is an X-linked genetic disorder caused by missing or defective Factor VIII, a clotting protein. Although it is passed down from parents to children, about 1/3 of cases are caused by a spontaneous mutation, a new mutation that was not inherited. Approximately 1 in 10,000 people have Hemophilia A.
BioMarin is a global biotechnology company that develops and commercializes innovative therapies for serious and life-threatening rare and ultra-rare genetic diseases. The Company's portfolio consists of seven commercialized products and multiple clinical and pre-clinical product candidates. For additional information, please visit www.biomarin.com . Information on BioMarin's website is not incorporated by reference into this press release.
Forward Looking Statements
BioMarin® is a registered trademark of BioMarin Pharmaceutical Inc.
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SOURCE BioMarin Pharmaceutical Inc.