FDA NewsPerspective

FDA committee recommends approval of Nucala for adults with severe asthma

An FDA advisory committee today voted unanimously in favor of approving Nucala for the treatment of severe asthma with eosinophilic inflammation in individuals aged 18 years and older.

However, the committee members voted against recommending use of the therapy in adolescents aged 12 to 17 years by a vote of 4-10.

The FDA’s Pulmonary-Allergy Drugs Advisory Committee voted 14-0 in favor of approving Nucala (mepolizumab, GlaxoSmithKline) in adults.

Twelve members from the committee voted safety of mepolizumab 100 mg subcutaneously (SC) administered once every 4 weeks in children aged 12 to 17 years had not been adequately demonstrated for treatment of severe asthma.

And nine of the committee members voted that efficacy data did not provide substantial evidence of a meaningful benefit of mepolizumab 100 mg SC once every 4 weeks for the treatment of severe asthma in children aged 12 to 17 years.

“There simply was little efficacy and safety data in that group of patients,” Ian Pavord, MD, professor of respiratory medicine at Oxford University, told Healio.com/Allergy. “Severe eosinophilic asthma is relatively unusual in an adolescent population and many asthma trials struggle to recruit adolescents with severe asthma. And I think the committee took the view that there wasn’t enough efficacy and safety data.”

The recommendation of mepolizumab in adults and non-recommendation in children followed the presentation of two phase 3 studies of mepolizumab for the treatment of severe asthma.

Mepolizumab effectively reduced daily oral corticosteroid use (OCS) while maintaining asthma control (OR = 2.39; 95% CI, 1.25-4.56) in 135 patients with severe asthma participating in a 24-week double blind, placebo-controlled, multicenter study evaluating the use of mepolizumab 100 mg SC, every 4 weeks compared with placebo in reducing daily OCS use.

Patients receiving mepolizumab also reported a significant improvement (0.52 points, P = .004) in their asthma control (ACQ-5 score) and their quality of life, measured by the St. George's Respiratory Questionnaire (5.8 points, P = .019).

In a second study, mepolizumab reduced time to first asthma exacerbation in 576 patients receiving mepolizumab 75 mg intravenously (28%) and 100 mg SC (24%) compared with placebo (45%) at 16 weeks.

Patients receiving mepolizumab — in the 32-week double blind, double-dummy, placebo-controlled, parallel group multicenter study — also experienced a reduction in their blood eosinophil count (83% reduction for IV and 86% for SC), which was maintained from week 12 for the duration of the study.

Pavord told Healio.com/Allergy that although he understood the committee’s stance on the adolescent population, mepolizumab would benefit the patient population.

“There certainly are adolescent patients who have severe asthma which is having a major impact on them that would respond to this treatment, so I think it’s very disappointing from their point of view,” he said.

Mepolizumab is currently not approved anywhere in the world.

Although the FDA is not required to follow the recommendations of the advisory committees, it often does. – by Ryan McDonald

Disclosure: Pavord reports advisory board and travel expenses from GlaxoSmithKline.

An FDA advisory committee today voted unanimously in favor of approving Nucala for the treatment of severe asthma with eosinophilic inflammation in individuals aged 18 years and older.

However, the committee members voted against recommending use of the therapy in adolescents aged 12 to 17 years by a vote of 4-10.

The FDA’s Pulmonary-Allergy Drugs Advisory Committee voted 14-0 in favor of approving Nucala (mepolizumab, GlaxoSmithKline) in adults.

Twelve members from the committee voted safety of mepolizumab 100 mg subcutaneously (SC) administered once every 4 weeks in children aged 12 to 17 years had not been adequately demonstrated for treatment of severe asthma.

And nine of the committee members voted that efficacy data did not provide substantial evidence of a meaningful benefit of mepolizumab 100 mg SC once every 4 weeks for the treatment of severe asthma in children aged 12 to 17 years.

“There simply was little efficacy and safety data in that group of patients,” Ian Pavord, MD, professor of respiratory medicine at Oxford University, told Healio.com/Allergy. “Severe eosinophilic asthma is relatively unusual in an adolescent population and many asthma trials struggle to recruit adolescents with severe asthma. And I think the committee took the view that there wasn’t enough efficacy and safety data.”

The recommendation of mepolizumab in adults and non-recommendation in children followed the presentation of two phase 3 studies of mepolizumab for the treatment of severe asthma.

Mepolizumab effectively reduced daily oral corticosteroid use (OCS) while maintaining asthma control (OR = 2.39; 95% CI, 1.25-4.56) in 135 patients with severe asthma participating in a 24-week double blind, placebo-controlled, multicenter study evaluating the use of mepolizumab 100 mg SC, every 4 weeks compared with placebo in reducing daily OCS use.

Patients receiving mepolizumab also reported a significant improvement (0.52 points, P = .004) in their asthma control (ACQ-5 score) and their quality of life, measured by the St. George's Respiratory Questionnaire (5.8 points, P = .019).

In a second study, mepolizumab reduced time to first asthma exacerbation in 576 patients receiving mepolizumab 75 mg intravenously (28%) and 100 mg SC (24%) compared with placebo (45%) at 16 weeks.

Patients receiving mepolizumab — in the 32-week double blind, double-dummy, placebo-controlled, parallel group multicenter study — also experienced a reduction in their blood eosinophil count (83% reduction for IV and 86% for SC), which was maintained from week 12 for the duration of the study.

Pavord told Healio.com/Allergy that although he understood the committee’s stance on the adolescent population, mepolizumab would benefit the patient population.

“There certainly are adolescent patients who have severe asthma which is having a major impact on them that would respond to this treatment, so I think it’s very disappointing from their point of view,” he said.

Mepolizumab is currently not approved anywhere in the world.

Although the FDA is not required to follow the recommendations of the advisory committees, it often does. – by Ryan McDonald

Disclosure: Pavord reports advisory board and travel expenses from GlaxoSmithKline.

    Perspective
    Anne-Marie Irani

    Anne-Marie Irani

    • The FDA Pulmonary-Allergy Drugs Advisory Committee's recommendation to approve mepolizumab (a humanized anti-IL 5 monoclonal antibody), given subcutaneoulsy every 4 weeks for the treatment of severe asthma with eosinophilic inflammation in subjects aged 18 years and older is a welcome development in a field that has seen little clinical progress over the past decade in spite of significant resources devoted to novel therapeutic approaches in this area.  On the other hand, the population of adolescents aged 12 to 18 years of age with severe asthma is not included in this recommendation, because of a paucity of efficacy and safety data in this age group. 

      This is an unfortunate situation as  it is precisely because there are fewer numbers of adolescents with severe eosinophilic asthma that it is difficult to recruit adequate number of them in clinical trials, yet, these patients would likely benefit from this treatment  as much if not more than older individuals with more chronic disease.  It would be helpful if guidelines were developed that would ease the way for approval of novel therapies in adolescents by reviewing safety and efficacy data in a young adult population.

      • Anne-Marie Irani, MD
      • Professor of Pediatrics and Medicine
        Children's Hospital of Richmond at VCU
    • Disclosures: Irani reports no relevant financial disclosures.