EMA’s human medicines committee (CHMP) has recommended extending the therapeutic indication of Uplizna (inebilizumab) to include the treatment of adult patients with active immunoglobulin G4-related disease (IgG4-RD).
IgG4-RD is a rare, chronic, autoimmune condition (a disease caused by the body’s own defence system attacking normal tissue) that can cause fibrosis (tissue scarring) and inflammations in one or multiple organs. Patients with IgG4-RD suffer from new or worsening signs and symptoms in one or more organs. The consequences of inflammation manifest gradually or acutely and can lead to irreversible organ damage and dysfunction. IgG4-RD normally affects people between the ages of 40 and 60.
There are currently no authorised medicines in the EU for the treatment of adults with IgG4-RD, and patients are commonly treated with glucocorticoids and other immunomodulatory medicines. Some patients show significant reductions in the size of lesions and improvement in laboratory test results, but others fail to achieve complete remission or relapse within one year. In addition, side effects associated with the use of glucocorticoids, including high blood pressure, high blood sugar, osteoporosis (thinning bones), a weakened immune system and muscle weakness, are more likely to occur in older patients. There is therefore a high unmet medical need for steroid-sparing treatments in patients with IgG4-RD.
Uplizna contains inebilizumab, a monoclonal antibody (a type of protein) that attaches to immune cells called B cells and destroys them. Uplizna is already approved to treat patients with neuromyelitis optica spectrum disorders (NMOSD).
The CHMP based its recommendation on the assessment of efficacy and safety data from a phase 3, randomised, double blind, 52-week clinical trial in 135 adult patients with active IgG4-RD who received either intravenous Uplizna or matching placebo on day 1, day 15, and week 26. The median time to the first treated IgG4-RD flare was significantly longer in patients receiving Uplizna. Similarly, of the 68 patients receiving Uplizna, only seven were treated for IgG4 RD flares, compared to 40 of the 67 patients receiving placebo. In addition, 58.8% of patients receiving Uplizna achieved corticosteroid-free, flare-free complete remission (a period without disease symptoms after treatment) at week 52, compared to 22.4% of patients receiving placebo.
The safety profile of Uplizna in patients with IgG4 RD or in patients with NMOSD was generally consistent. The most common side effects were infections (including urinary tract infections, nasopharyngitis and upper respiratory tract infections), joint pain, back pain and low levels of lymphocytes, a type of white blood cell.
The opinion adopted by the CHMP is an intermediary step on Uplizna’s path to patient access. The opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide extension of the therapeutic indication. Once an extension has been granted, decisions about price and reimbursement will take place at the level of each Member State, taking into account the potential role or use of these medicines in the context of the national health system of that country.
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