Results from a phase III study demonstrate benefit with mepolizumab over placebo in patients with hypereosinophilic syndrome

Hypereosinophilic syndromes (HES) are a group of rare myeloproliferative neoplasms (MPN) characterized by elevated eosinophil levels. Abnormally high eosinophil counts eventually contribute to organ damage and, if left untreated, can become life threatening. Interleukin-5 (IL-5) is a major growth factor for eosinophils, and the anti-IL-5 monoclonal antibody, mepolizumab, has been approved for the treatment of several eosinophilic diseases. The question remains whether mepolizumab could be effective in the HES setting.

Results from the phase III study evaluating the efficacy and safety of mepolizumab vs placebo in patients with HES, were presented by Florence Roufosse¹ during the virtual edition of the 25th European Hematology Association (EHA) Annual Congress, and the data are summarized here. 

Study design

• Phase III, randomized, double blind, multicenter, placebo-controlled trial conducted as a parallel group study
• Primary endpoint: Proportion of patients who experienced a flare in the 32-week study period (defined as either, a clinical manifestation of HES requiring an increase of ≥ 10 mg prednisolone or similar for 5 days, or an increase/the addition of cytotoxic or immunosuppressive therapy, or having received more than two courses of oral corticosteroids during treatment)
• Secondary endpoints: Time to first flare, annual rate of flares and the proportion of patients who experienced a flare in weeks 20–32 of the study period

Patient eligibility

• Patients were aged ≥ 12 years with a diagnosis of HES* ≥ 6 months prior to the trial onset
• Patients received HES therapy ≥ 4 weeks prior to the baseline visit
• Patients had uncontrollable HES defined as
  • ≥ two flares within 12 months of trial onset
  • blood eosinophil count ≥ 1,000 cells/µL

*FIP1L1-PDGFRA-negative HES

Treatment

• Eligible patients (N = 108) underwent screening followed by a 32-week treatment period during which they were randomized to receive existing HES therapy plus
  • 300 mg subcutaneous mepolizumab (n = 54) or placebo (n = 54)

Results

Patient characteristics

• Patient characteristics at the time of enrollment are presented in Table 1

Table 1. Baseline patient characteristics¹

Efficacy

• A 50% reduction in the proportion of patients who experienced a flare or withdrew from the study was observed in the mepolizumab vs placebo groups (Figure 1A)
• A 66% reduction in the annualized rate of flares was observed in the mepolizumab vs placebo groups (Figure 1B)
• A 53% reduction in the proportion of patients who experienced a flare or withdrew from the study in the final 12 weeks of the study period was observed in the mepolizumab vs placebo groups (Figure 1C)
• Mepolizumab induced a significant reduction in blood eosinophil levels, which plateaued after three doses, when compared with placebo

Figure 1. Patient responses to mepolizumab. A, proportion of patients who experienced a flare or withdrew from the study across the 32-week study period. B, annualized rate of flare. C, proportion of patients who experienced a flare or withdrew from the study during weeks 20–32 of the study period. CI, confidence interval

Safety

• Frequencies of adverse events (AEs) were similar in the placebo and mepolizumab arms
• No serious AEs were considered to be treatment related
• The most frequently observed on-treatment AEs are presented in Table 2

Table 2. Most common on-treatment AEs reported in ≥ 10% of patients in any group¹

Conclusions

Data from this study have demonstrated that, when added to patient standard of care, mepolizumab significantly reduces the frequency of flares and blood eosinophil levels when compared with placebo, and no new safety concerns were associated with mepolizumab. Professor Roufosse concluded that the findings from this study suggest that mepolizumab may offer patients with FIP1L1-PDGFRA-negative HES an effective option for management, which is currently an area of unmet clinical need.