ICER Releases Draft Evidence Report on Gene Therapies for Hemophilia A and B

Despite $2.5 million placeholder price tags, the Institute for Clinical and Economic Review draft evidence report considers gene therapy cost-effective versus comparators in both hemophilia A and B.

The Institute for Clinical and Economic Review (ICER) has released a draft evidence report concluding that gene therapies for hemophilia A and hemophilia B are cost-effective in the long term despite their high costs. This is especially true for hemophilia B, the report found.

Hemophilia A and B both put patients at risk of excessive and even life-threatening bleeding. The standard treatment options are currently clotting factor administration for both types, as well as prophylaxis with the monoclonal antibody emicizumab for hemophilia A.

The ICER report evaluated the clinical efficacy and value of the gene therapy etranacogene dezaparvove compared with factor IX prophylaxis in patients with hemophilia B. It also provided updates to a prior assessment of valoctocogene roxaparvovec versus emicizumab or factor VII prophylaxis in hemophilia A. Both gene therapies are one-time infusions, and neither is FDA approved.

Etranacogene dezaparvovec, an adeno-associated virus serotype 5 (AAV5)-mediated gene therapy for hemophilia B, boosts production of an active variant of factor IX after a one-time infusion. Patients who received the treatment saw an 80% reduction in treated joint bleeds, as well as reductions in other bleeds, compared with bleed rates while on factor prophylaxis before etranacogene dezaparvovec. Patients who responded to the gene therapy did not need additional factor prophylaxis in the 18 months post-therapy. The treatment burden was also reduced dramatically, as patients would previously need weekly factorIX therapy at a minimum.

While uncontrolled study design, a small number of patients, and relatively short follow-ups are limitations of etranacogene dezaparvovec research, the report concludes there is at least a small net health benefit to gene therapy over factor prophylaxis for patients with hemophilia B. And even at a placeholder price of $2.5 million, cost-savings and projected quality-adjusted life years (QALYs) led ICER to deem etranacogene dezaparvovec the more cost-effective option.

Valoctocogene roxaparvovec, an AAV5-mediated gene therapy for hemophilia A, is a one-time infusion that facilitates production of an active variant of factor VIII. There is only indirect evidence to compare valoctocoge neroxaparvovec with emicizumab for hemophilia A, but ICER determined that the benefits of gene therapy in this population to be at least as substantial as emicizumab versus factor prophylaxis. Valoctocogene roxaparvovec does pose a greater risk of initial adverse events compared with emicizumab, however.

The report also concludes that valoctocogene roxaparvovecmay provide a comparable, small, or substantial health benefit to patients versus factor VIII prophylaxis, although there is insufficient evidence to come to a definitive conclusion. As with etranacogenede zaparvovec, however, the long-term outcomes after treatment with valoctocogene roxaparvovec are not yet clear.

Valoctocogene roxaparvovec was also found to be more cost-effective than the comparators in the report. Again, despite a placeholder $2.5 million cost of treatment, the cost-savings and projected QALYs led ICER to consider gene therapy to be the favorable option compared with the hemophilia A comparators.

While neither gene therapy option is approved by the FDA, the agency has accepted a Biologics License Application (BLA) from CSL Behring for etranacogene dezaparvovec, and BioMarin is expected to resubmit a BLA for valoctocogene roxaparvovec by the end of September of 2022.


Gene therapy for hemophilia B and an update on gene therapy for hemophilia A: effectiveness and value. ICER. September 13, 2022. Accessed September 16, 2022.