DOPTELET 20 mg (avatrombopag)

Key points

Unfavourable opinion for reimbursement in the treatment of primary chronic immune thrombocytopenia (ITP) in adult patients who are refractory to other treatments.

Role in the care pathway?

In France, the treatment of primary immune thrombocytopenia (ITP) (or idiopathic thrombocytopenic purpura) is based primarily on the French national diagnostic and care protocol (PNDS) updated in 2017.

ITP requires the initiation of specialised care, in liaison with the general practitioner.

In the absence of clinical or haematological signs of ITP severity and consequences on quality of life (asthenia, impact on schooling, etc.), no treatment or corticosteroid/IgIV therapy (on demand or programmed) may be proposed.

In the event of chronic ITP present for more than 12 months, several second-line treatments may be proposed in adults; few of these treatments have been evaluated in randomised controlled studies. Only thrombopoietin receptor agonists (romiplostim, eltrombopag) and azathioprine have an indication in ITP validated by an MA. Rituximab has a temporary recommendation for use (RTU) in this indication. Splenectomy is also one of the second-line therapeutic options in the event of ITP present for at least 12 months. Despite the increased risks of serious infections and venous and/or arterial thrombosis in adults, splenectomy is the only treatment that has been established as being curative. There is no consensus with respect to its role in the hierarchical sequence of second-line treatments and it may be performed before or after rituximab and/or TPO-R agonists.

In the absence of a consensus-based care pathway, the choice of treatment must remain personalised and be discussed on a case-by-case basis.

In accordance with the most recent Committee opinions relative to TPO-R agonists (eltrombopag and romiplostim), the occasional use of TPO-R agonists may be considered in the treatment of marked thrombocytopenia refractory to first-line treatments, in the event of severe bleeding syndrome, in the context of preparation for a surgical procedure or pending the effect of already initiated second-line therapy (according to expert opinion). Outside these occasional uses, given the primarily suspensive effect and uncertainties with respect to the long-term safety data of these medicinal products, they may be considered in the treatment of chronic ITP refractory to first-line treatments (e.g. corticosteroids, immunoglobulins) and following the failure of one of the second-line treatments (immunosuppressant, rituximab or splenectomy) or as an alternative to these treatments when they are not considered to be appropriate.

It should be noted that after the development of the 2017 French national diagnostic and care protocol (PNDS), a new medicinal product - fostamatinib (TAVLESSE) - was granted a marketing authorisation in chronic ITP in adults “refractory to other treatments”. The Committee issued a favourable opinion for its funding and considered that, on the basis of available data, fostamatinib was:

• a last-resort treatment for multirefractory chronic ITP resistant to second-line treatments (which, according to the 2017 PNDS, include splenectomy, TPO-R agonists [switches included] and rituximab),
• a therapeutic option in patients not having undergone splenectomy, multirefractory to medicinal treatments, when splenectomy is deemed to be inappropriate by reference or expert centres.

This medicinal product is not available at present.

Role of the medicinal product in the care pathway

Considering the limitations of the clinical studies having assessed DOPTELET (avatrombopag) in refractory chronic ITP, and, in particular:

• the absence of direct comparison with the other therapies available, despite this being feasible, in a context when two medicinal products belonging to the same TPO-R agonist therapeutic class are already available,
• the marked heterogeneity of the population included in the placebo-controlled study in terms of previous ITP treatments, which does not make it possible to have access to robust data in patients having exhausted all the treatment options (only 35%, 19% and 37% of patients respectively had undergone previous treatment with splenectomy, rituximab or TPO-R agonists), or to identify a subpopulation of patients that might benefit from avatrombopag treatment,
• demonstration of its efficacy in comparison with placebo only in terms of biological response, on endpoints of debatable relevance (cumulative number of weeks for which the platelet count was ≥ 50 × 10⁹/L in the absence of rescue therapy, and platelet response at D8), and uncertainties with respect to the effect size observed given the very numerous major protocol deviations occurring during the study,
• the absence of demonstrated impact on the occurrence of haemorrhage or quality of life,

the Committee considers that DOPTELET (avatrombopag) has no role in the care pathway in the treatment of primary chronic immune thrombocytopenia (ITP) in adult patients who are refractory to other treatments.