This document addresses gene therapy for hemophilia, a congenital medical condition in which the blood does not clot normally due to lack of sufficient blood-clotting proteins known as clotting factors. There are several forms of hemophilia, the most common of which are hemophilia A, which involves a deficiency in clotting factor VIII, and hemophilia B, which involves a deficiency in clotting factor IX. Gene therapy products for hemophilia use a virus vector with a working copy of the missing gene attached (factor VIII and factor IX for hemophilia A and B, respectively).

Position Statement

Medically Necessary:

Etranacogene dezaparvovec-drlb is considered medically necessary in individuals who meet all of the following criteria:

1. Diagnosis of hemophilia B; and
2. Age 18 years or older; and
3. Baseline factor IX level is less than 1 international unit (IU)/deciliter (dL) (or 1% endogenous factor IX); and
4. No contraindications to infusion (if any of the following are present, treatment is contraindicated):
   1. Active infection; or
   2. Immunosuppressive disorder; or
   3. Liver cirrhosis; or
   4. Active hepatitis B or C; or
   5. Alanine transaminase (ALT) greater than 3 times the upper limit of normal; or
   6. Bilirubin greater than 3 times the upper limit of normal; or
   7. Alkaline phosphatase greater than 3 times the upper limit of normal; or
   8. International normalized ratio (INR) greater than1.4.; or
   9. Prior infusion of etranacogene dezaparvovec-drlb;
      and
5. Poor disease control meeting one or more of the following:
   1. One or more episodes of spontaneous bleeding into a joint or the central nervous system while receiving routine prophylaxis factor replacement therapy; or
   2. Four or more episodes of soft tissue bleeding in an 8-week period while receiving routine prophylaxis factor replacement therapy; or
   3. At least 12 bleeding episodes over the previous year while receiving on-demand therapy.

Valoctocogene roxaparvovec-rvox is considered medically necessary in individuals who meet all of the following criteria:

1. Diagnosis of hemophilia A; and
2. Age 18 years or older; and
3. Baseline factor VIII level is less than 1 international unit (IU)/deciliter (dL) (or 1% endogenous factor VIII); and
4. No contraindications to infusion (if any of the following are present, treatment is contraindicated):
   1. Detectable pre-existing immunity to the AAV5 capsid as measured by AAV5 transduction inhibition or AAV5 total antibodies; or
   2. History of factor VIII inhibitor; or
   3. Active infection; or
   4. Immunosuppressive disorder; or
   5. Liver cirrhosis; or
   6. Active hepatitis B or C; or
   7. Alanine transaminase (ALT) greater than 3 times the upper limit of normal; or
   8. Bilirubin greater than 3 times the upper limit of normal; or
   9. Alkaline phosphatase greater than 3 times the upper limit of normal; or
   10. International normalized ratio (INR) greater than1.4.; or
   11. Prior infusion of valoctocogene roxaparvovec-rvox;
       and
5. Poor disease control meeting one or more of the following:
   1. One or more episodes of spontaneous bleeding into a joint or the central nervous system while receiving routine prophylaxis factor replacement therapy; or
   2. Four or more episodes of soft tissue bleeding in an 8-week period while receiving routine prophylaxis factor replacement therapy; or
   3. At least 12 bleeding episodes over the previous year while receiving on-demand therapy.

Investigational and Not Medically Necessary:

Gene therapy for hemophilia is considered investigational and not medically necessary when the criteria above are not met and in all other situations.