About Hemophilia B
Hemophilia B is a life-threatening degenerative disease. People with the condition are particularly vulnerable to bleeds in their muscles, internal organs, and joints, 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. This can reduce joint bleeding events, prevent life-threatening bleeds, and preserve joint function. However, infusions can be cumbersome, painful and veins can fibrose over time, making ongoing treatment difficult. A person's immune system may also generate inhibitors against the replacement factor, negating its benefit. In addition, many people receiving prophylaxis are forced to plan their lives around the highs and lows of their FIX levels, which rise immediately after an infusion but drop over time -- leaving them especially vulnerable to bleeds and pain in the days before their next infusion. Most troubling, prophylactic FIX replacement therapy sometimes fails to control unobservable micro-bleeds in the joints, meaning that the degeneration can continue despite regular infusions. Missing an infusion may also the increase their likelihood of a life-threatening bleed or even premature death.
About Gene Therapy in Hemophilia B
Gene therapy has the potential to make a functional cure possible in hemophilia B. Gene therapy achieves this with modified non-infectious viruses called "vectors" that can enter certain cells. Vectors act as delivery trucks, carrying a package of genetic instructions to specific cells. Once delivered, the package acts like a generator that plugs into the cellular machinery, allowing a person to produce their own stable levels of FIX. A certain type of vector, called an adeno-associated virus, or AAV, dissolves after delivering its package. The genetic instructions remain, but never actually become a part of a person's own DNA.
About Etranacogene Dezaparvovec
Etranacogene dezaparvovec (also known as CSL222 and EtranaDez, previously known as AMT-061) uses a specific type of AAV, called AAV5, as its delivery vehicle. The AAV5 vector carries the patent-protected 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 the 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.