CABLIVI 10 mg (caplacizumab)

Key points

Favourable opinion for reimbursement in the treatment of adults experiencing an episode of acquired thrombotic thrombocytopenic purpura (aTTP), in conjunction with plasma exchange and immunosuppression.

Unfavourable opinion for reimbursement in adolescents of 12 years of age and older weighing at least 40 kg in this indication.

 What therapeutic improvement?

In adults in combination with standard therapy including plasma exchange and immunosuppression, therapeutic improvement compared to standard treatment of the aTTP episode.

Role in the care pathway?

aTTP requires rapid diagnosis, its management constituting a therapeutic emergency for which daily plasma exchanges should be rapidly implemented in combination with immunosuppression (generally corticosteroids ± rituximab). The urgent initiation of plasma exchanges as soon as possible is essential, since these enable the supply of ADAMTS13, the elimination of abnormal von Willebrand factor (vWF)  multimers and anti ADAMTS13 auto-antibodies. The confirmation of the diagnosis, provided by the measurement of ADAMTS13 activity, occurs after emergency treatment initiation.

Role of the medicinal product in the care pathway

In adults

CABLIVI (caplacizumab) is a first-line treatment for adults experiencing an episode of acquired thrombotic thrombocytopenic purpura (aTTP), in conjunction with plasma exchange and immunosuppression. The available data does not enable the definition of a typology of patients derive a greater benefit from the treatment with CABLIVI (caplacizumab).

CABLIVI (caplacizumab) is active on the initial microthrombi formation phase. Treatment with CABLIVI (caplacizumab) should therefore be initiated early on during standard treatment including plasma exchanges and immunosuppression, upon clinical presumption of an aTTP episode, without waiting for confirmation.

CABLIVI (caplacizumab) is initiated by intravenous injection before plasma exchange, then continued by daily subcutaneous administration after each plasma exchange, for the entire duration of daily plasma exchange treatment, followed by daily subcutaneous injections for 30 days after termination of plasma exchange treatment. For patients in clinical remission and whose ADAMTS13 activity has normalised, no data concerning discontinuation before the end of the 30-day post-PE caplacizumab treatment is available.

In clinical studies, the relapse rate was higher at the end of treatment in patients receiving caplacizumab and maintaining an undetectable ADAMTS13 activity. Consequently, if, at the end of this 30-day period, signs indicate that disease activity has not been resolved, the immunosuppression treatment should be optimised and subcutaneous administration of CABLIVI (caplacizumab) should be continued until the signs of the underlying disease have been resolved (in particular sustained normalisation of ADAMTS13 activity). The phase 3 study (HERCULES - ALX0681-C301) scheduled weekly monitoring of the activity of this protease. There is no data available on the long-term efficacy, in particular on relapses, and safety of CABLIVI (caplacizumab).

In adolescents above 12 years of age weighing at least 40 kg

Given the very scarce clinical data available, based only on a small number of case studies published in the literature, and in the absence of conclusive clinical data concerning its efficacy and safety in this population, CABLIVI (caplacizumab) has no role in the care pathway in adolescents above 12 years of age weighing at least 40 kg.