Inhaled Anti-TSLP May Be Promising New Treatment for Adults With Mild Asthma

After careful consideration, the American Thoracic Society canceled its annual meeting that was to take place in Philadelphia, Pennsylvania from May 15-20, because of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Although the live events will not proceed as planned, our readers can still find coverage of research that was scheduled to be presented at the meeting. A virtual event is being planned for later this year.

CSJ117, formulated as an engineered powder in hard capsules for delivery to the lungs via dry powder inhaler, may be the first inhaled anti-thymic stromal lymphopoietin (TSLP) treatment for adults with mild asthma, according to research intended to be presented at the American Thoracic Society (ATS) International Conference. (Select research will be available in a virtual format later this year.)

TSLP, an epithelial cell-derived cytokine, may play an important role in asthmatic airway inflammation. CSJ117 is a potent neutralizing antibody fragment directed against human TSLP. Researchers conducted a proof-of-concept, double-blind, placebo-controlled study in 28 patients with mild, atopic asthma who were randomly assigned to receive a daily dose of CSJ117 (n=15) or placebo (n=13) for 12 weeks. An allergen inhalation challenge was conducted at screening, day 42, and day 84.

The primary efficacy variable was the late asthmatic response (LAR) as measured 3 to 7 hours after the allergen challenge at day 84, and primary safety evaluations were the incidence and severity of adverse events (AEs). Secondary end points included early asthmatic response (EAR) as measured within 2 hours after the allergen challenge, and minimum forced expiratory volume in 1 second (FEV₁) during LAR and EAR. Fractional exhaled nitric oxide (FeNO) levels were also measured.

Researchers found that CSJ117 attenuated both LAR and EAR at day 84, and compared with the placebo group, patients in the CSJ117 group had a significantly higher minimum FEV₁ during the LAR on day 84 (P =.038). During the LAR, the time-adjusted area under the curve percentage decrease and maximum decrease in FEV₁ from before the allergen inhalation challenge were significantly less in the CSJ117 group compared with placebo (4.20% vs 11.38%; P =.008 and 9.28% vs 17.70%; P =.029; respectively). Similarly, during the EAR, both measures were smaller in the CSJ17 group vs the placebo group.

A reduction in FeNO in the CSJ117 group compared with placebo was also observed throughout the study. The researchers noted that AEs were mostly mild and balanced between the 2 groups, and that there were no serious AEs or discontinuations as a result of the AEs.

“These findings support TSLP’s role in allergen-induced airway responses and airway inflammation, and suggest that anti-TSLP may be a promising, new therapeutic class for asthma treatment,” the researchers concluded.

Reference

Gauvreau GM, Hohlfeld JM, Grant S, et al. Efficacy and safety of an inhaled anti-TSLP antibody fragment in adults with mild atopic asthma. Am J Respir Crit Care Med. 2020;201:A4207.

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