At the American Thoracic Society (ATS) conference, positive Phase III results of GSK’s interleukin 5 (IL-5) inhibitor Nucala (mepolizumab) were presented for eosinophilic granulomatosis with polyangiitis (eGPA).
IL-5 regulates eosinophils, which are thought to induce pathogenic effects in eGPA. Nucala has demonstrated a reduction in blood eosinophil count in patients with eosinophilic asthma and other hypereosinophilic syndromes, marking strong potential for Nucala as a treatment of eGPA. Ample need exists for the development of drugs for eGPA, as there are currently no approved biologics for this indication. Approval of Nucala would signify the first biologic to target the eGPA space, offering the drug first-to-market advantage, a significant opportunity for GSK.
Also known as Churg-Strauss Syndrome, ePGA is a form of anti-neutrophil cytoplasmic antibody (ANCA) associated small vessel vasculitis defined by eosinophil-rich and necrotising granulomatous inflammation, often of the respiratory tract. First-line therapy consists of glucocorticoids (GC), most commonly prednisone (5-10mg/day). This is prescribed in combination with immunosuppressants such as cyclophosphamide or azathioprine, which all present their own sets of side effects.
While GCs are very effective and provide immediate relief of vasculitis symptoms, their efficacy declines as the dose is reduced to a level better tolerated by patients. Many patients require increased doses of prednisone to achieve remission, which leads to more frequent adverse events. Furthermore, the long-term use of immunosuppressants such as cyclophosphamide and azathioprine is associated with serious adverse events, including lymphoma and death. Alternative treatment options, such as Nucala, are needed to quickly and effectively reduce steroid use and to minimise side effects.
In a Phase III, placebo controlled, double blind, parallel group, multi-center study, patients with eGPA and a history of relapsing or refractory disease on stable therapy (prednisolone/prednisone 7.5-50mg/day with or without immunosuppressive therapy for at least four weeks) were randomised to receive Nucala (300mg, n=68) or placebo (n=68) both via a subcutaneous injection every four weeks for 52 weeks, in addition to standard of care. After Week 4, glucocorticoid dose could be tapered.
Duration of accrued remission (Birmingham Vasculitis Activity Score of zero and a prednisolone / prednisone dose of no more than 4mg a day) over 52 weeks, one of the co-primary endpoints, was significantly longer in patients treated with Nucala compared with placebo (p<0.001). In addition, a significantly higher proportion of Nucala-treated patients compared with patients treated with placebo were in remission at weeks 36 and 48 (32% versus 3%, p<0.001), the other co-primary endpoint. Secondary endpoints, including average GC dose from Week 49-52 (median dose of 5mg/day in Nucala-treated patients compared with 10mg a day in patients treated with placebo) and time to first eGPA relapse were met as well.
Nucala is the only biologic in late-stage development for eGPA. Should it gain approval and launch, Nucala is expected to have an edge in the eGPA market space. Physicians’ familiarity with the biologic will also be beneficial, as it is indicated as an add-on treatment for patients with severe asthma with an eosinophilic phenotype.
GlobalData anticipates that Nucala will hold a substantial advantage in the biologic market for eGPA, garnering sales of $29.1 million across the seven major pharmaceutical markets of the US, France, Germany, Italy, Spain, the UK, and Japan in 2024.
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