— Duration of benefit with gene therapies and risks for rare side effects remain major uncertainties —

— Fair pricing benchmarks suggest upper bounds for price of valoctocogene roxaparvovec at approximately $1.9 M and for etranacogene dezaparvovec at approximately $2.9 M —

— At the November 18 virtual public meeting, ICER’s independent appraisal committee will review the evidence, hear further testimony from stakeholders, and deliberate over these treatments’ comparative clinical effectiveness, other potential benefits, and long-term value for money —

BOSTON, November 2, 2022 – The Institute for Clinical and Economic Review (ICER) today posted its revised Evidence Report assessing the comparative clinical effectiveness and value of etranacogene dezaparvovec (CSL Behring) for hemophilia B. ICER also updated the previous Hemophilia A assessment on valoctocogene roxaparvovec (Roctavian™, BioMarin).  

“Hemophilia is a serious, lifelong disease, that leads to pain and disability as a result of repeated bleeds into joints and muscles, and can limit options for education, employment, and recreation,” said David Rind, MD, ICER’s Chief Medical Officer. “Prophylaxis with factor replacement is burdensome and does not achieve normal clotting, although for patients with hemophilia A, emicizumab has reduced burdens and improved outcomes. The new gene therapies can result in successfully-treated patients appearing ‘cured’ for at least a period of time.  During this period these gene therapies will eliminate the need for expensive prophylactic treatment. However, the duration of this ‘cure’ and the safety of therapies remain important uncertainties. At least with valoctocogene roxaparvovec, patients will eventually return to needing prophylaxis.”

This Evidence Report will be reviewed at a virtual public meeting of the CTAF (CTAF) on November 18, 2022. The CTAF is one of ICER’s three independent evidence appraisal committees comprising medical evidence experts, practicing clinicians, methodologists, and leaders in patient engagement and advocacy.

A draft version of this report was previously open for a four-week public comment period. The updated Evidence Report and voting questions reflect changes made based on comments received from patient groups, clinicians, drug manufacturers, and other stakeholders. Detailed responses to public comments can be found here.

Key Clinical Findings

Patients treated with etranacogene dezaparvovec had an 80% reduction in treated joint bleeds and similar reductions in other bleeds when compared with their bleeding rates on factor prophylaxis prior to gene therapy. However, there is still considerable uncertainty about the duration of benefit and the risk of uncommon harms with etranacogene dezaparvovec. We conclude that there is moderate certainty of a small or substantial health benefit with high certainty of at least a small net health benefit (B+) for etranacogene dezaparvovec compared with factor IX prophylaxis. 

There is no direct evidence comparing valoctocogene roxaparvovec with emicizumab.  Indirect evidence suggests that the short-term reduction in bleeding rates with valoctocogene roxaparvovec compared with factor prophylaxis are at least as great as that observed with emicizumab compared with factor prophylaxis, but the duration of benefit is clearly limited and there is uncertainty about uncommon harms. Thus, we conclude that there is low certainty about the net health benefit (I) for valoctocogene roxaparvovec compared with emicizumab. With these same considerations and the greater burdens and lower efficacy of factor VIII prophylaxis, we conclude that there is moderate certainty of a comparable, small, or substantial health benefit with high certainty of at least a comparable net health benefit (C++) for valoctocogene roxaparvovec compared with factor VIII prophylaxis. 

Key Cost-Effectiveness Findings

The cost-effectiveness modeling for these gene therapies shows health gains and the potential for substantial cost offsets due to elimination of the need for very expensive prophylactic treatment.  However, ICER has previously noted the ethical and practical concerns related to factoring in all potential cost offsets over a lifetime horizon when calculating a Health Benefit Price Benchmark (HBPB) for a potentially curative treatment.  In the case of these two gene therapies, more than 99% of the traditional cost-effectiveness “value” is generated by cost offsets of eliminating prophylactic treatment that itself is widely considered to be far too expensive to be cost-effective.  Therefore, to calculate the HBPB for these gene therapies we have applied our alternative cost-effectiveness methodology that shares the savings from cost offsets between the life science company and the health system.

Under this shared savings scenario, cost offsets are limited to $150,000 per year in calculation of the HBPB, which is intended to suggest fair pricing in alignment with the benefits to patients.  For valoctocogene roxaparvovec the HBPB ranges from $1.958 million to $1.963 million; and the relevant HBPB for etranacogene dezaparvovec is $2.93 million to $2.96 million.

ICER’s HBPB is a price range suggesting the highest US price a manufacturer should charge for a treatment, based on the amount of improvement in overall health patients receive from that treatment, when a higher price would cause disproportionately greater losses in health among other patients in the health system due to rising overall costs of health care and health insurance. In short, it is the top price range at which a health system can reward innovation and better health for patients without doing more harm than good.

About ICER

The Institute for Clinical and Economic Review (ICER) is an independent non-profit research institute that produces reports analyzing the evidence on the effectiveness and value of drugs and other medical services. ICER’s reports include evidence-based calculations of prices for new drugs that accurately reflect the degree of improvement expected in long-term patient outcomes, while also highlighting price levels that might contribute to unaffordable short-term cost growth for the overall health care system.

ICER’s reports incorporate extensive input from all stakeholders and are the subject of public hearings through three core programs: the California Technology Assessment Forum (CTAF), the Midwest Comparative Effectiveness Public Advisory Council (Midwest CEPAC), and the New England Comparative Effectiveness Public Advisory Council (New England CEPAC). These independent panels review ICER’s reports at public meetings to deliberate on the evidence and develop recommendations for how patients, clinicians, insurers, and policymakers can improve the quality and value of health care. For more information about ICER, please visit ICER’s website.