Dive Brief:
- GlaxoSmithKline's IL5 antagonist Nucala for eosinophilic chronic obstructive pulmonary disease comes before the Food and Drug Administration's Pulmonary-Allergy Drugs Advisory Committee Meeting on Wednesday and tone of the briefing document isn't so positive.
- The FDA briefing documents questions the importance of eosinophil count and the lack of precedent, and raises concerns about the validity of the IL-5 pathway as a target, particularly considering the recent failure of two clinical trials for AstraZeneca's Fasenra.
- The briefing documents also query the design and data from the two Phase 3 clinical trials, citing the lack of a statistically significant reduction in a primary endpoint – moderate-to-severe COPD exacerbations – in the second study, the lack of meaningful differences in secondary endpoints, and the issues potentially caused by the inclusion of people with asthma.
Dive Insight:
Nucala (mepolizumab) was first approved in the U.S. in November 2015, as the first anti-IL5 treatment for adults and adolescents with severe asthma with an eosinophilic phenotype. Marketing authorization in Europe followed in December 2015. Since then it has been approved for the treatment of eosinophilic granulomatosis with polyangiitis (EGPA).
Glaxo sought U.S. approval in eosinophilic chronic obstructive pulmonary disease (COPD) in November 2017, along with data from its Phase 3 METREX and METREO studies.
Nucala's key rivals in the biologic treatment of severe asthma are Teva Pharmaceutical's Cinqair (reslizumab), which was approved for the indication in March 2016, and Fasenra in November 2017.
COPD is the next market in GSK's sights. The drug would be used as an add-on maintenance treatment for people with COPD, to support other therapies, and would only be used in the eosinophilic subtype of the disease. Eosinophilic COPD is proving a hard nut to crack. In May, AstraZeneca pulled back from submitting Fasenra for COPD after a second miss in the disease. Teva is not currently pursuing this market for Cinqair.
The outcomes of Wednesday's panel will be eagerly watched. In a one-hundred page briefing document, the committee members have been given the clinical data to consider. They will discuss the role of Nucala as an add-on treatment to reduce worsening in COPD guided by blood eosinophil counts, and then vote on Wednesday on the efficacy, safety and the benefit-risk profile of the drug.
The discussions will be guided by a set of questions. Efficacy will make up a large proportion of the discussion, looking at a number of points, including: the adequacy of dose exploration; the impact of unmeasured variables such as asthma history and previous treatments; the clinical significance of the efficacy data, including the lack of statistically significant results for the primary endpoint in one of the two trials, and the lack of robust results for key secondary endpoints. The discussion will also look at the uncertainty of the definition of the eosinophilic COPD phenotype and how this affects the interpretation of the efficacy results.