New England Journal of Medicine publishes positive final results from phase 1/IIa study of BIVV001 in people with severe haemophilia A. Sanofi + Sobi

The New England Journal of Medicine published positive final results from the phase 1/IIa trial evaluating the safety, tolerability and pharmacokinetics of BIVV001 (rFVIIIFc-VWF-XTEN) in adult patients with severe haemophilia A . BIVV001 is an investigational factor VIII therapy designed to provide higher bleed protection in a once-weekly prophylactic treatment regimen. Sobi and Sanofi collaborate on the development and commercialization of BIVV001. Phase 1/IIa study results: EXTEN-A is an open-label, multicentre study that evaluated the safety, tolerability and pharmacokinetics of BIVV001 in both a 25 IU/kg (n=6) and a 65 IU/kg (n=8) dose cohort of participants aged 19-63 years with severe haemophilia A (NCT03205163). In the trial, participants received a single dose of conventional recombinant factor VIII (rFVIII) followed, after a washout period, by either a single 25 IU/kg or 65 IU/kg dose of BIVV001. Primary endpoints included occurrence of adverse events and development of inhibitors. Key findings included:BIVV001 was generally well tolerated with no inhibitor development detected through 28 days post-dose. During the study period no adverse events of allergic reaction, anaphylaxis or clinically meaningful treatment-related adverse events were reported. In the 65 IU/kg dose cohort, a single dose of BIVV001 achieved a FVIII half-life of 43 hours, a greater than three-fold increase from the 13-hour half-life observed with rFVIII. Mean factor VIII activity level was greater than 51% and in the normal range for four days, and 17% at seven days post BIVV001 infusion.In the 25 IU/kg cohort, a single dose of BIVV001 achieved a FVIII half-life of 38 hours, a four-fold increase from the 9-hour half-life observed with rFVIII, with a mean factor activity level of 5% at seven days post BIVV001 infusion. Factor activity levels refer to the amount of factor VIII in a person's blood and are used to determine the severity of a person's disease. Participants enrolled in the EXTEN-A trial have severe haemophilia A (factor levels of <1%). moderate haemophilia a is characterized by factor levels of 1-5%, and mild haemophilia a is from 5-40%. phase iii xtend-1 study: the safety and efficacy of bivv001 is currently being evaluated in the ongoing phase iii xtend-1 study in previously treated patients ?12 years of age (n="150)" with severe haemophilia a. xtend-1 is an open-label, non-randomized interventional study with two parallel assignment arms. participants in the prophylaxis arm will receive a weekly prophylactic 50 iu kg dose of bivv001 for 52 weeks. participants in the on-demand arm will receive bivv001 (50 iu kg) on demand for 26 weeks followed by a switch to bivv001 weekly prophylaxis for another 26 weeks. a potential to transform factor replacement therapy for haemophilia a : the half-life of conventional factor viii therapy is constrained by the von willebrand factor's (vwf) chaperone effect, which is believed to limit the time the factor remains in the body. bivv001 is the first factor viii therapy under development that has been shown to break through the vwf ceiling, thus allowing people with haemophilia a to potentially move toward normal factor activity levels for the majority of the week. see- "bivv001 fusion protein as factor viii replacement therapy for hemophilia a."- barbara a. konkle, m.d., amy d. shapiro, m.d., doris v. quon, m.d., ph.d., janice m. staber, m.d., et al.-september 10, 2020 n engl j med 2020; 383:1018-1027 doi: 10.1056 nejmoa2002699.>