The European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the therapeutic indication of Uplizna (inebilizumab, Amgen Europe) to include treatment of adult patients with active immunoglobulin G4-related disease (IgG4-RD). The decision marks the first authorized medicine in the EU for this rare autoimmune condition.

Uplizna is already authorized in the EU as a monotherapy for adult patients with anti-aquaporin-4 immunoglobulin G seropositive neuromyelitis optica spectrum disorders.

Significant Unmet Need

IgG4-RD is a rare, chronic autoimmune condition that causes fibrosis and inflammation in one or multiple organs, typically affecting individuals aged 40-60 years. The disease manifests with new or worsening symptoms that can lead to irreversible organ damage and dysfunction if left untreated.

There are currently no medicines authorized in the EU specifically for the treatment of adults with this disease. Standard treatment often involves glucocorticoids and other immunomodulatory medicines, but some patients do not achieve complete remission or may relapse within a year. Also, the use of glucocorticoids can lead to side effects such as high blood pressure, high blood sugar, and osteoporosis, especially in older patients, highlighting a significant need for steroid-sparing treatments.

Uplizna contains inebilizumab, a monoclonal antibody that targets and depletes CD19+ B cells, which may be effective for treating patients with this multiorgan, relapsing fibroinflammatory disorder.

Clinical Evidence and Safety Profile

The CHMP's recommendation is based on positive data from the phase 3 MITIGATE trial, involving 135 adults with active IgG4-RD. Participants were randomized to receive either intravenous inebilizumab or placebo over a 52-week treatment period (on day 1, day 15, and week 26), with both groups receiving identical glucocorticoid tapers. 

Results showed that 10% of participants in the inebilizumab group experienced at least one flare, compared with 60% in the placebo group. Additionally, 58.8% of patients receiving Uplizna achieved corticosteroid-free, flare-free complete remission at week 52, compared with 22.4% receiving placebo. The annualized flare rate was significantly lower with inebilizumab than placebo.

The safety profile remained consistent with that observed in patients with neuromyelitis optica spectrum disorder. Most common adverse events included infections such as urinary tract infections, nasopharyngitis, and upper respiratory tract infections, along with joint pain, back pain, and decreased lymphocyte levels. 

After European Commission approval, individual Member States will make decisions regarding pricing and reimbursement, considering the medicine's role within their national health systems. 

Detailed recommendations for Uplizna use will be described in the updated summary of product characteristics, which will be published on the EMA website in all official EU languages after the European Commission grants the marketing authorization change.