Nucala

The safety and efficacy of Nucala were established in 3 double-blind, randomized, placebo-controlled trials (ClinicalTrials.gov Identifier: NCT01000506, NCT01691521 and NCT01691508) in patients 12 years of age and older with severe asthma on currently available medicines.

Study patients were given either Nucala or placebo every 4 weeks as an add-on asthma treatment. In the 2 confirmatory trials (N=711), patients were required to have blood eosinophils of ≥150 cells/mcL at screening (within 6 weeks of dosing) or blood eosinophils of ≥300 cells/mcL within 12 months of enrollment.

Treatment with Nucala resulted in fewer exacerbations requiring hospitalization and/or emergency department visits, and a longer time to the first exacerbations when compared with placebo.

Patients treated with Nucala saw greater reductions in their daily maintenance oral corticosteroid dose, while maintaining asthma control vs patients treated with placebo.

A significant improvement in lung function however was not seen with Nucala, as measured by the volume of air exhaled by patients in 1 second.

Approval in the younger patient population was supported by evidence from clinical trials in adults and adolescents. In addition, findings from an open-label trial (ClinicalTrials.gov Identifier: NCT02377427) evaluating the pharmacokinetics, pharmacodynamics, and safety of Nucala in patients 6 to 11 years old (N=36) showed that a dose of 40mg administered subcutaneously (SC) every 4 weeks resulted in similar drug exposure as a dose of 100mg SC in adults and adolescents.

Eosinophilic Granulomatosis With Polyangiitis

Approval was based on data from a 52-week trial where patients were randomly assigned to receive either Nucala 300mg or placebo subcutaneously once every 4 weeks while continuing oral corticosteroid (OCS) therapy (OCS was tapered starting at week 4). Disease remission while on an OCS dose of ≤4mg of prednisone was considered the primary efficacy outcome. 

Results showed that compared with placebo, Nucala-treated patients achieved a significantly greater accrued time in remission, with a higher proportion of patients in the Nucala group achieving remission at both week 36 and week 48.

Moreover, significantly more patients who received Nucala achieved remission within the first 24 weeks and remained in remission for the remainder of the 52-week study.

Hypereosinophilic Syndrome

Approval was based on data from a 32-week, randomized, double-blind, placebo-controlled phase 3 study (ClinicalTrials.gov Identifier: NCT02836496) that assessed the efficacy and safety of Nucala in 108 patients aged 12 years and older with severe HES, defined as having at least 2 HES flares within the past 12 months and a blood eosinophil count of 1000 cells/µL or higher. 

Patients were randomly assigned to receive Nucala 300mg subcutaneously every 4 weeks or placebo. The primary endpoint was the proportion of patients who experienced an HES flare during the 32-week treatment period.

Findings showed that patients treated with Nucala experienced significantly fewer HES flares compared with placebo (56% vs 28%, respectively; P =.002). The risk of first HES flare over the treatment period was 66% lower for patients treated with Nucala vs placebo (hazard ratio, 0.34; 95% CI 0.18-0.67; P =.002). Treatment with Nucala resulted in a statistically significant 66% reduction in the annualized rate of HES flares compared with placebo.

Approval was based on data from the randomized, double-blind, parallel group phase 3 SYNAPSE study (ClinicalTrials.gov Identifier: NCT03085797), which evaluated the efficacy and safety of Nucala as an add-on maintenance treatment in over 400 adults with CRSwNP.

All patients had a history of prior surgery and were in need of further surgery due to severe symptoms and increased size of their polyps. Patients were randomly assigned to receive Nucala 100mg subcutaneously every 4 weeks or placebo for 52 weeks, in addition to standard of care (eg, mometasone furoate nasal spray).

The co-primary endpoints were change from baseline to week 52 in total endoscopic nasal polyp score (NPS; 0-8 scale) as graded by independent blinded assessors and change from baseline in nasal obstruction visual analog scale (VAS) score (0-10 scale) during weeks 49 to 52.

At the end of the 52 week treatment period, patients treated with Nucala had a statistically significant improvement in bilateral NPS at week 52 (mean difference vs placebo, -0.93 [95% CI, -1.31, -0.55]) and nasal obstruction VAS score from weeks 49 to 52 (mean difference vs placebo, -1.86 [95% CI, -2.53, -1.19]).

The proportion of patients who had surgery was significantly reduced by 57% (hazard ratio, 0.43; 95% CI, 0.25-0.76) in the group treated with Nucala vs placebo. Mepolizumab treatment was also associated with statistically significant improvement in loss of smell and with reduced need for systemic corticosteroids.