FDA approves Nucala as add-on therapy for certain COPD patients
Adults with eosinophilic phenotype, uncontrolled disease seen benefiting
The U.S. Food and Drug Administration (FDA) has approved Nucala (mepolizumab) as an add-on maintenance treatment for certain people with chronic obstructive pulmonary disease (COPD).
The treatment, from GSK, is specifically indicated for adults with COPD whose disease is not adequately controlled with other therapies and who have an eosinophilic phenotype — meaning high numbers of eosinophils, a type of immune cell that contributes to lung inflammation in many COPD patients.
In this patient population, Nucala was shown to be significantly superior to a placebo at reducing the rates of moderate or severe COPD exacerbations (sudden periods of COPD symptom worsening) when added to standard triple inhaled therapy. It is administered via a subcutaneous, or under-the-skin, injection every four weeks.
“The approval of Nucala in the US provides an important option for COPD patients,” Kaivan Khavandi, PhD, senior vice president and global head of respiratory, immunology and inflammation research and development at GSK, said in a company press release. “Long-term follow-up studies have demonstrated that exacerbations are the single most important predictor of future risk, with particularly poor outcomes in those requiring hospital visits or admissions.”
An initial application was rejected by the FDA in 2018, with the agency asking for more clinical trial data confirming the therapy’s efficacy in this subgroup of COPD patients.
Trials with COPD patients
Regulatory agencies in the European Union and China are considering Nucala’s approval for treating COPD patients with an eosinophilic phenotype. An application has also been submitted to authorities in Canada.
Nucala is an antibody-based therapy designed to reduce the number of eosinophils by suppressing IL-5, a signaling protein involved in the cells’ growth, survival, and activation. This is expected to lessen type 2 inflammation, which is marked by high eosinophils and thought to contribute to COPD-related lung inflammation.
The therapy has been approved in the U.S. and elsewhere as a treatment for other inflammatory diseases in which eosinophils can play a role, including some types of asthma and ANCA-associated vasculitis.
The FDA’s approval of Nucala for COPD was based on data from two Phase 3 clinical trials, MATINEE (NCT04133909) and METREX (NCT02105948), which collectively enrolled more than 1,600 adults with inadequately controlled COPD and an eosinophilic phenotype.
In both trials, participants were randomly assigned to receive either Nucala or a placebo once every four weeks for at least a year, and the main goal was to see if Nucala could reduce rates of moderate or severe COPD exacerbations.
Results from both MATINEE and METREX showed that Nucala significantly reduced the risk of moderate or severe exacerbations relative to the placebo, by roughly 20% in both studies. A prespecified analysis from MATINEE showed that the therapy also reduced rates of exacerbations requiring emergency department visits and/or hospitalization by about 35%.
According to GSK, Nucala is the only approved biologic, or treatment derived from living organisms, that’s been evaluated in COPD patients with an eosinophilic phenotype characterized by a blood eosinophil count threshold as low as 150 cells per microliter of blood (cells/uL). Blood eosinophil count, or BEC, can be measured with a simple blood test.
About 70% of people with COPD in the U.S. whose disease is inadequately controlled on inhaled triple therapy and who continue to experience exacerbations have a BEC of at least 150 cells per microliter, according to GSK.
“Today there is hope for improved care for COPD patients with an eosinophilic phenotype, including those with a BEC threshold as low as [150 cells/uL] who need new options like Nucala to support their treatment journey,” Khavandi said.
Jean Wright, MD, CEO of the COPD Foundation, welcomed the news of Nucala’s approval.
“COPD isn’t just a disease, it’s a relentless cycle,” Wright said. “For individuals living with COPD, managing exacerbations is an ongoing challenge, even with inhaled maintenance therapy. Biologics like [Nucala] are providing renewed optimism for those affected by COPD.”
Nucala’s most common side effects include back pain, diarrhea, and cough, according to its prescribing information. The therapy should not be given to people with a history of allergic reactions to any of the treatment’s ingredients.
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