MARBURG,
'As the first gene therapy candidate for hemophilia B, this pivotal regulatory milestone brings
The MMA is supported by positive findings from the pivotal HOPE-B trial, the largest gene therapy trial in hemophilia B to date. Hemophilia B patients classified as having a severe bleeding phenotype treated with etranacogene dezaparvovec demonstrated reduced adjusted annualized bleed rate (ABR) by 64% and demonstrated superiority to prophylaxis treatment at 18 months post-treatment compared to a 6-month run in period. Additionally, there was stable and durable increases in mean Factor IX (FIX) activity levels. Etranacogene dezaparvovec was specifically designed to make near-normal blood-clotting ability possible by addressing the underlying cause of the condition: a faulty F9 gene that causes a deficiency in clotting Factor IX (FIX).
'The acceptance of etranacogene dezaparvovec for review by the EMA furthers our relentless pursuit to improve the lives and well-being of those living with hemophilia B and other rare and serious medical disorders,' said
The multi-year clinical development was led by
About Hemophilia B
Hemophilia B is a life-threatening degenerative disease. People with the condition are particularly vulnerable to bleeds in their joints, muscles, and internal organs, leading to pain, swelling, and joint damage. Current treatment includes life-long prophylactic infusions of FIX to temporarily replace or supplement low levels of the blood-clotting factor.
About Hemophilia B
Hemophilia B is a life-threatening degenerative disease. People with the condition are particularly vulnerable to bleeds in their joints, muscles, and internal organs, leading to pain, swelling, and joint damage. Current treatment includes life-long prophylactic infusions of FIX to temporarily replace or supplement low levels of the blood-clotting factor.
About Gene Therapy in Hemophilia B
Gene therapy has the potential to make a functional cure possible in hemophilia
About Etranacogene Dezaparvovec
Etranacogene dezaparvovec (also known as CSL222, previously known as AMT-061) uses a specific type of AAV, called AAV5, as its vector. The AAV5 vector carries the Padua gene variant of Factor IX (FIX-Padua), which generates FIX proteins that are 5x-8x more active than normal. Preclinical and clinical data show that AAV5-based gene therapies may be clinically effective in up to 95 percent of hemophilia B patients with pre-existing antibodies to AAV vectors, thereby potentially increasing patient eligibility for treatment compared to other AAV gene therapy product candidates.
About the Pivotal HOPE-B Trial
The pivotal Phase III HOPE-B trial is a multinational, open-label, single-arm study to evaluate the safety and efficacy of etranacogene dezaparvovec. Fifty-four adult hemophilia B patients classified as having a severe bleeding phenotype and requiring prophylactic FIX replacement therapy were enrolled in a prospective, six-month observational period during which time they continued to use their current standard of care therapy to establish a baseline Annual Bleeding Rate (ABR). After the six-month lead-in period, patients received a single intravenous administration of etranacogene dezaparvovec at the 2x10^13 gc/kg dose. Patients were not excluded from the trial based on pre-existing neutralizing antibodies (NAbs) to AAV5. A total of 54 patients received a single dose of etranacogene dezaparvovec in the pivotal trial, with 53 patients completing at least 18 months of follow-up. The primary endpoint in the pivotal HOPE-B study was 52-week ABR after achievement of stable FIX expression compared with the six-month lead-in period. For this endpoint, ABR was measured from month seven to month 18 after infusion, ensuring the observation period represented a steady-state FIX transgene expression. Secondary endpoints included assessment of FIX activity and statistical superiority of ABR after dosing.
Results from the pivotal HOPE-B study demonstrated that etranacogene dezaparvovec produced mean FIX activity of 39.0 IU/dL at six months and 36.9 IU/dL at 18 months post infusion. After the six-month lead-in period post-infusion, the adjusted annualized bleeding rate (ABR) (1.51) for all bleeds was reduced by 64 percent (p=0.0002) and all FIX-treated bleeds was reduced by 77 percent (3.65 to 0.83; p
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