CSL Behring's Hemgenix has been recommended for managed access as a treatment option for adults with moderately severe or severe haemophilia B (congenital factor IX [FIX] deficiency) who do not have anti-FIX antibodies. The recommendation is contingent upon adherence to the conditions set in the managed access agreement for etranacogene dezaparvovec. The treatment, priced at £2.6 million per dose, shows promise in addressing this genetic disorder.
Clinical Trial Evidence
The primary evidence for Hemgenix comes from the ongoing HOPE-B trial, a Phase 3, open-label, single-dose, single-arm multinational study. This trial involves 54 adult males with moderately severe or severe haemophilia B who previously received routine FIX prophylaxis treatment. The trial had a lead-in period of at least six months where participants were on FIX prophylaxis before transitioning to etranacogene dezaparvovec treatment. Outcomes from the lead-in period were compared to those in the post-treatment follow-up period, with data presented up to 24 months and additional data up to 36 months.
Significant Reduction in Bleeding Rates
The HOPE-B trial's primary outcome was the annualized bleeding rate (ABR). Results showed substantial reductions in various types of bleeds:
The adjusted ABR for all bleeding episodes decreased from 4.19 to 1.51, a 64% reduction.
The adjusted annualized spontaneous bleeding rate dropped from 1.52 to 0.38, a 75% reduction.
The adjusted annualized joint bleeding rate fell from 2.35 to 0.46, an 80% reduction.
The adjusted ABR for bleeds requiring FIX treatment decreased from 3.65 to 0.99, a 73% reduction.
Despite these improvements, it was noted that at 7 to 24 months post-treatment, 27 out of 54 participants experienced bleeds, averaging 2.7 bleeds per person compared to 3.4 bleeds per person during the lead-in period. Experts suggest this may be due to patients needing time to distinguish between joint pain and actual bleeds after receiving the treatment.
Economic and Clinical Analysis
A cohort-based Markov model was presented to evaluate the cost-effectiveness of Hemgenix. This model considered various health states based on bleeding events, including 'no bleed,' 'non-joint bleed,' 'joint bleed,' and 'death.'
The company conducted both fully incremental and pairwise analyses to compare the cost-effectiveness of Hemgenix against FIX prophylaxis treatments. Clinical experts indicated that the choice of prophylaxis treatment in practice depends on factors such as dosing schedule, FIX activity levels, bleeding patterns, mechanism of action, and availability.
The committee found that using a basket of FIX prophylaxis treatments weighted by NHS market share as a comparator was most appropriate. They noted that Hemgenix, combined with subsequent FIX prophylaxis after treatment failure, had lower costs and higher quality-adjusted life years (QALYs) than the comparator.
Long-Term Effectiveness and Managed Access
The committee expressed concerns about the long-term durability of Hemgenix's treatment effects. While the treatment showed cost-effectiveness in the company's base case, the treatment effect needed to persist significantly beyond trial data to remain cost-effective. The uncertainty around the long-term durability of the treatment led the committee to conclude that routine NHS use could not be recommended without additional data.
Conclusion
The committee recognized the potential of Hemgenix to significantly improve the lives of individuals with severe haemophilia B. However, due to uncertainties regarding long-term effectiveness, it recommended Hemgenix for managed access rather than routine NHS use.
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