Reason for request
Key points
Favourable opinion for reimbursement for the treatment of progressive familial intrahepatic cholestasis (PFIC) type 1 or 2 (with the exception of the BSEP3 subtype) in patients aged 6 months or older.
Unfavourable opinion for reimbursement in other types of PFIC.
What therapeutic improvement?
Therapeutic improvement in the management of patients aged 6 months or older with PFIC type 1 or 2 (with the exception of the BSEP3 subtype).
Role in the care pathway?
The current treatment for PFIC is based on treatments with a non-specific action, used to control clinical symptoms and signs: nutritional supplements, prevention of vitamin deficiencies, treatment of hepatic manifestations, including severe pruritus. Medicinal products use off-label for the disease include ursodesoxycholic acid (except in PFIC type 3 for which it has an MA in France), rifampicin, hydroxyzine, antihistamines, naltrexone. None of these medicinal products have demonstrated a long-term effect or modify the prognosis. Hence, recourse to surgery is necessary in the majority of patients, with, in particular, the performance of external biliary diversion surgery, and liver transplant as a last-resort.
The main reason for recourse to biliary diversion is pruritus not controlled by medicinal products, particularly in the event of PFIC type 2. In addition, patients having undergone successful biliary diversion surgery can still have high serum bile acid levels and severe pruritus.
As a last resort, liver transplantation is considered: this eliminates cholestasis in patients with PFIC types 1 et 2. However, in the event of PFIC type1, extra-hepatic manifestations can occur following transplantation.
Therefore, there is currently no medicinal product specifically indicated in the event of PFIC (in particular types 1 and 2, which are the most common) and the medical need in these sometimes rare genetic conditions remains high.
Role of the medicinal product in the care pathway
In patients with PFIC type 1 and 2, the Transparency Committee considers that BYLVAY (odevixibat) is a second-line treatment that should be prescribed in addition to first-line medical treatment (UDCA +/- rifampicin), when the prescriber deems it necessary to continue therapeutic efforts in order to reduce serum bile acid levels and/or reduce pruritus in order to improve the patient’s quality of life.
In patients with the BSEP3 subtype of PFIC type 2 (odevixibat not effective), and in other types of PFIC, the role of BYLVAY (odevixibat) cannot be determined in the absence of clinical data.
Clinical Benefit
Substantial |
The Committee deems that the clinical benefit of BYLVAY (odevixibat) is substantial in the treatment of progressive familial intrahepatic cholestasis (PFIC) type 1 or 2 (with the exception of the BSEP3 subtype) in patients aged 6 months or older.
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Insufficient |
The Committee deems that the clinical benefit of BYLVAY (odevixibat) is insufficient to justify public funding cover in the other types of PFIC. |
Clinical Added Value
moderate |
The Transparency Committee considers that BYLVAY (odevixibat) in combination with the medicinal treatments currently used, such as ursodesoxycholic acid (UDCA) or rifampicin (off-label) provides a moderate clinical added value (CAV III) in the treatment of PFIC type 1 and 2 (excluding subtype BSEP3). |