- Date 16 December 2020
- Documents : 9
- Economic analysis
- History
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Reason for request
Key points
Favourable opinion for reimbursement only in the treatment of chronic hepatitis delta virus (HDV) infection in plasma (or serum) HDV-RNA positive adult patients with compensated liver disease, in combination with a maintenance therapy against HBV and in the event of failure, intolerance or contraindication to PEGylated interferon alpha.
Unfavourable opinion for reimbursement in other situations, including bulevirtide monotherapy, in particular.
What therapeutic improvement?
Therapeutic improvement in the management of the disease.
Role in the care pathway?
PEGylated interferon alpha (PEG-IFNα-2a) is currently the only medicinal product to have demonstrated its antiviral efficacy against HDV and to be recommended for the treatment of this infection. It reduces the viral load of HDV and can be used in combination or otherwise with another anti-HBV treatment with nucleoside/nucleotide inhibitors (intrinsically ineffective against HDV). The minimum treatment duration is one year, irrespective of the evolution of the response during treatment. It should be noted that interferon is poorly tolerated (influenza-like illness, depression, etc.) and that the tolerance reduces with age and in the event of advanced fibrosis. Intolerance leads to treatment discontinuation in 10 to 30% of cases within the first 6 months. In addition, many patients are not eligible for treatment with interferon alpha due to a contraindication or advanced disease, in particular: auto-immune hepatitis, treatment with immunosuppressive therapy, psychiatric or decompensated thyroid disorders, severe renal impairment and decompensated cirrhosis.
Liver transplantation may be considered in the event of fulminant hepatitis or end-stage liver disease.
The prevention of hepatitis D involves vaccination against hepatitis B.
Role of the medicinal product in the care pathway
HEPCLUDEX (bulevirtide) is a first or second-line option, in combination with maintenance therapy for hepatitis B virus (HBV) (nucleoside or nucleotide analogue), in the management of chronic hepatitis delta virus (HDV) infection in plasma (or serum) HDV-RNA positive adult patients with compensated liver disease, in combination with a maintenance therapy against HBV and in the event of failure, intolerance or contraindication to PEGylated interferon alpha.
The Committee highlights the fact that exacerbations of hepatitis occurring after treatment discontinuation possibly related to a virologic rebound, as identified in the risk management plan (RMP), require the long-term maintenance of treatment, for which the optimal duration is not known. In addition, given that HDV inhibits the replication of HBV, the risk of reactivation of HBV in the event of control of HDV replication by bulevirtide requires maintenance of optimal concomitant HBV treatment.
Special recommendations
In view of the current uncertainties concerning the efficacy, safety and conditions of use of HEPCLUDEX (bulevirtide) and the complexity of management (clinical stage, optimal treatment duration an patient follow-up), the Committee recommends restricting the prescription of HEPCLUDEX (bulevirtide) to physicians experienced in the management of patients with chronic HDV infection and following discussion at a multidisciplinary team meeting.
Clinical Benefit
| Substantial |
The Committee deems that the clinical benefit of HEPCLUDEX (bulevirtide) is substantial only in the treatment of chronic hepatitis delta virus (HDV) infection in plasma (or serum) HDV-RNA positive adult patients with compensated liver disease, in combination with a maintenance therapy against HBV and in the event of failure, intolerance or contraindication to PEGylated interferon alpha; |
| Insufficient |
The Committee deems that the clinical benefit of HEPCLUDEX (bulevirtide) is insufficient to justify public funding cover in the other situations, including bulevirtide monotherapy, in particular. |
Clinical Added Value
| minor |
Considering:
and despite:
the Committee considers that HEPCLUDEX (bulevirtide), in combination with maintenance therapy for HBV, provides a minor clinical added value (CAV IV) in the care pathway for the treatment of patients infected with HDV for whom it is impossible to establish a suppressive antiviral treatment regimen with PEGylated alpha interferon, particularly in the event of failure, intolerance or contraindication.
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