Etranacogene dezaparvovec-drlb gene therapy for patients with hemophilia B (congenital factor IX deficiency)

Abstract

Introduction: Congenital hemophilia B (HB) is an X-linked bleeding disorder resulting in Factor IX (FIX) deficiency and bleeding of variable severity. There is no cure for HB. Typical management consists of prophylactic intravenous (IV) recombinant or plasma-derived FIX infusions. Etranacogene dezaparvovec-drlb (Hemgenix, AMT-061) is an adeno-associated virus serotype 5 (AAV5) vector containing a codon-optimized Padua variant of the human F9 gene with a liver-specific promoter. Etranacogene dezaparvovec-drlb received FDA approval on 22 November 2022 for the treatment of HB in adult patients who use FIX prophylaxis therapy, have current or historical life-threatening hemorrhage, or have experienced repeated, serious spontaneous bleeding episodes.

Areas covered: This drug profile discusses the safety and efficacy of etranacogene dezaparvovec-drlb in patients with HB.

Expert opinion: Etranacogene dezaparvovec-drlb therapy results in stable and sustained expression of near-normal to normal FIX levels in patients with HB regardless of neutralizing antibodies to AAV5 up to a titer of 678. Its use has led to significant reduction in bleeding and FIX prophylaxis. Etranacogene dezaparvovec-drlb was well tolerated; however, 17% of patients required corticosteroid therapy for alanine aminotransferase (ALT) elevation. Etranacogene dezaparvovec-drlb therapy marks the beginning of an exciting era in HB treatment and opens questions regarding treatment longevity and long-term safety.

Keywords: Annual bleeding rate; Hemgenix; Padua variant; etranacogene dezaparvovec-drlb; factor IX (FIX); gene therapy; glucocorticoid therapy; hemophilia B.