TAVNEOS (avacopan)

Key points

Approval of reimbursement of TAVNEOS (avacopan) in the treatment of adult patients with severe and active granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA), in combination with rituximab or cyclophosphamide.

Therapeutic progress?

A therapeutic advance in the management of adult patients with severe and active granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MP).

Role in therapeutic strategy?

The goals of ANCA vasculitis management are to induce remission and prevent relapse, while limiting treatment-related adverse events and disease sequelae.

In France, the therapeutic strategy for inducing remission in severe and active GPA and PAM is based on the French recommendations of the French Vasculitis Study Group (GFEV) (2013), the EULAR European recommendations (2016), and the HAS national diagnosis and care protocol (PNDS 2019). Management is multidisciplinary and coordinated by a hospital doctor in conjunction with a reference centre for rare autoimmune and systemic diseases or a centre of expertise.

The treatment of severe forms of GPA and PAM combines corticosteroids with long-term immunosuppressive agents for more than 18 months. An initial induction therapy phase of approximately 3 to 6 months aims to attain remission of the disease.

In the induction therapy for remission of systemic GPA and PAM, rituximab can be prescribed as a first-line treatment along with cyclophosphamide. The choice of treatment is left to the clinician's discretion when patients are managed for a first episode of the disease. The decision takes into account the patient's history, pre-existing morbidity factors, the disease to be treated and the patient's opinion. Rituximab should be prescribed preferentially for women of childbearing age, particularly those over 30 years of age. These immunosuppressive treatments are given in combination with a high initial dose of corticosteroids. After an initial three-week course of treatment at a dose of 1 mg/kg/day of prednisone equivalent, the aim is to reduce and then discontinue corticosteroids on a tapering schedule, while maintaining remission. The total duration of corticosteroid therapy varies from six months (North American protocols) to 18-24 months (European protocols). In France, it is usually 6 to 12 months according to a tapering schedule in which the main benchmarks are approximately 20 mg/day at 3 months, 10 mg/day at 6 months and 5 mg/day at one year of prednisone equivalent.

Current induction therapy achieves remission in more than 80% of GPA and PAM cases. After remission has been achieved, relapses, which occur in more than half of GPA patients and in about 30% of PAM patients at 5 years, warrant maintenance therapy (with rituximab as the conventional treatment) in order to consolidate remission and limit the risk of relapse.

Role of the medicinal product

TAVNEOS (avacopan), the first selective human complement receptor 5a (C5aR1) antagonist, is a new first-line treatment option in combination with rituximab or cyclophosphamide for the treatment of adult patients with severe and active granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA).

TAVNEOS (avacopan) is particularly indicated for adult patients with severe and active GPA or PAM who are at risk of decompensation from high-dose corticisteroids, or who are identified as being at high risk of developing complications from high-dose corticosteroids.

However, the Committee notes that TAVNEOS (avacopan) has no role for patients with GPA or PMA who are intubated/ventilated due to severe intra-alveolar haemorrhage and/or severe renal impairment (estimated glomerular filtration rate < 15 ml/min), as these patients were not evaluated in the phase III ADVOCATE study.

Special recommendations

• Other requests

The Committee regrets the lack of data on the use of TAVNEOS (avacopan) in the paediatric population in which the partial cortisone sparing provided by avacopan may be of interest.

Furthermore, the Committee hopes that clinical studies on this treatment can soon be put in place in the paediatric population.