HEPCLUDEX (bulevirtide) - Hepatitis delta virus (HDV) adult and paediatric patients 3 years of age and older

The clinical benefit of HEPCLUDEX (bulevirtide) is substantial in the Market autorisation (MA)indication.

Considering:

• preliminary data (MYR 202 and MYR 203 studies) previously assessed at the time of initial listing (Transparency Committee opinion of 16/12/2020) having demonstrated:
  • a virologic efficacy against HDV, in combination with a nucleoside/nucleotide analogue active against HBV, in patients in whom pegylated interferon alpha has failed or is poorly tolerated (reduction by at least 2 log or conversion to negative viral load in approximately 50% of patients after 24 weeks, but with an undetectable viral load in only 4%),
  • achievement of a combined response (virologic response and ALT normalisation) in only 20% of patients after 24 weeks,
• new data supporting the previously assessed findings:
  • comparative phase 3 (MYR 301) trial versus delayed treatment, having demonstrated a combined response after 48 weeks, with both a virologic response (undetectable HDV RNA [< LLOQ, lower limit of quantitation, target not detected] or an HDV RNA reduction of ≥ 2 log10 IU/mL]) and ALT normalisation in 44.9% (95% CI [30.7%; 59.8%] of treated patients,
  • phase IIb study (MYR 204) not having demonstrated a superiority of bulevirtide 2 mg (administered for 96 weeks) in combination with pegylated interferon for a determined period (administered for 48 weeks) compared to pegylated interferon alone for 48 weeks, on the percentage of patients having achieved undetectable HDV RNA at 24 weeks after the scheduled end of treatment (32% versus 16.4%, p = 0.26),
• the fact that the effects of bulevirtide are not maintained in the event of treatment discontinuation, even after 96 weeks of treatment (MYR 204 study); it is therefore necessary to continue the treatment in the long term. To date, the optimal treatment duration is not known,
• a good safety profile that is better than that of interferon, although marked by an important identified risk in the context of the Risk Management Plan (RMP): hepatitis exacerbation after drug discontinuation, possibly associated with virologic rebound; and there are no long-term safety data concerning patients with total bile salt elevations induced by the medicinal product,
• the substantial medical need, particularly in patients in whom pegylated interferon alpha has failed or is poorly tolerated, and in the absence of an alternative in this situation,
• the absence of clinical data in the paediatric population, for which the MA is extrapolated on the basis of clinical data in adults and pharmacodynamic/pharmacokinetic data in the paediatric population obtained only by simulation,

the Committee considers that HEPCLUDEX (bulevirtide) provides a minor Clinical Added Value (CAV IV) in the care pathway for the treatment of patients infected with HDV in the context of the recommendations issued by the HAS.