GDC-0214 Well-Tolerated for Patients with Mild Asthma

August 8, 2020

In a study presented virtually at ATS 2020, investigators find 15 mg of the study drug resulted in a 43% decrease in FeNO.

GDC-0214 could be a beneficial option for patients with mild asthma by inhibiting various Janus Kinase (JAK) pathways.

In data planned for presentation at the American Thoracic Society (ATS) 2020 International Conference, a team, led by Honglin Chen, Senior Scientific Researcher, Genentech, tested GDC-0214 as a treatment for patients with mild asthma to reduce fractional exhaled nitric oxide (FeNO), a common JAK1-depenendnt IL-4 and IL-13 pathway biomarker.

The Janus Kinase pathway mediates activity for several asthma-relevant cytokines, including IL-4 and IL-13. However, GDC-0214, a potent, small molecule JAK1 inhibitor developed for inhaled delivery, has been safe and effective in past studies involving health volunteers.

In the double-blind, randomized, placebo-controlled, phase 1, proof-of-activity study, the investigators tested inhaled GDC-0214 at multiple dose levels in 36 patients. The team examined patients between 18-65 years old with physician-diagnosed asthma for at least 6 months with FeNO greater than 40 ppb, controlled with as-needed reliever medication.

The study consisted of 4 sequential ascending-dose cohorts mg QD, 4-mg QD, 15-mg QD, and 15-mg BID) with 6-12 patients each.

After receiving 4 days of blinded placebo, the patients were randomized 2-to-1 to GDC-0214 or placebo for an additional 10 days.

The investigators sought primary outcomes of the percent change in FeNO during the active treatment period and assessed pharmacokinetics, safety, and tolerability.

In the study there were 6 participants in each of the first 2 cohorts (1-mg QD; 4- mg QD) and 12 in each of the last 2 cohorts (15-mg QD; 15-mg BID). The mean age was 28 years old, with 54% of the patient population being female.

Overall, patients were diagnosed an average of 17 years prior to enrollment and had a mean FeNO of 93 ppb at baseline.

There were no significant treatment differences observed in the 1 mg and 4 mg dosing groups when compared to placebo, while FeNO was reduced by 23% (18 ppb difference) compared to placebo in the 15 mg QD arm and by 43% (45 ppb difference) in the 15 mg BID dose arm.

The investigators also found higher plasma exposures, which reflects higher lung concentrations, correspond with greater FeNO reductions.

There were no dose-limiting adverse events, serious adverse events, or treatment discontinuations. The most common adverse events in the study were asthma symptoms, upper respiratory tract infections, and headache.

There were also no major imbalances in adverse events or laboratory finding between the different treatment groups.

“Treatment with inhaled JAK inhibitor, GDC0214, for 10 days resulted in a dose-dependent reduction in FeNO in patients with mild asthma, and was found to be well tolerated, without evidence of systemic toxicity,” the authors wrote.

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The study, “Inhaled JAK Inhibitor GDC-0214 Reduces Exhaled Nitric Oxide in Patients with Mild Asthma,” was published online by ATS 2020.