REGN1908/1909 prevented cat allergen-induced early asthmatic responses
Published: August 3, 2022
Cat allergens are a common cause of allergic disease worldwide. The main allergen in cat dander is Felis domesticus 1 (Fel d 1), which is a persistent trigger for allergic rhinitis and asthma symptoms. Therefore, treatments that target both the upper and lower airway are of interest in cat allergy. Nose and eye symptoms of allergy, or rhinoconjunctivitis, is typically managed with antihistamines and intranasal corticosteroids; however, patients with poorly controlled symptoms may receive allergen-specific immunotherapy (AIT). The use of AIT for cat allergy is associated with a risk of adverse reactions and is contraindicated in those with uncontrolled or severe asthma. An alternative treatment strategy for those with allergies and asthma triggered by specific allergens is passive immunotherapy, whereby novel blocking immunoglobulin (Ig)G antibodies that bind to specific allergens are administered. REGN1908 and REGN1909 are IgG antibodies that bind to Fel d 1, which are in development as a combination (REGN1908/1909) passive immunotherapy for the treatment of cat allergy.
In a recent article in The Journal of Allergy and Clinical Immunology (JACI), de Blay et al report on the efficacy and safety of REGN1908/1909 in preventing cat allergen-induced early asthmatic responses in cat-allergic patients with mild asthma. In the placebo-controlled study, 56 cat-allergic patients were randomized to a single dose of REGN1908/1909 600 mg (n=29) or placebo (n=27). Patients were exposed to cat allergen in an environmental exposure unit (EEU), which was used to trigger cat allergen-induced early asthmatic responses. An early asthmatic response was defined as a greater than or equal to 20 percent reduction in air able to be forced from the lungs in one second (forced expiratory volume in 1 second; FEV1). FEV1 was measured for up to 4 hours in the EEU, including twice during the screening period and four times after dosing (with either REGN1908/1909 or placebo), on days 8, 29, 57, and 85.
A single-dose of REGN1908/1909 was shown to prevent the reduction of FEV1 and early asthmatic response in cat-allergic patients with mild asthma. Most patients who received REGN1908/1909 did not have an early asthmatic response by four hours in the EEU (the last timepoint tested), whereas placebo-treated patients experienced an early asthmatic response on days 8, 29, 57, and 85, with most placebo-treated patients experiencing an early asthmatic response within 1 hour in the EEU. In addition, patients who received REGN1908/1909 had a greater tolerance to cat-allergen compared with placebo-treated patients. Skin test reactivity to cat allergen was also substantially reduced in patients who received REGN1908/1909 versus placebo (nominal P < .001). REGN1908/1909 was generally well tolerated, with no serious adverse events or deaths reported. Administration of single-dose REGN1908/1909 600 mg maintained a mean combined total drug concentration in serum above 10 mg/L for approximately 85 days.
As a single dose of REGN1908/1909 was shown to have substantial and rapid effects lasting for up to 85 days, as well as being generally well tolerated, it offers the possibility for a new approach to treat cat allergy and asthma triggered by cat allergen. The results of this study also support the further development of therapies based on combinations of allergen-specific IgG antibodies as a convenient option for several specific allergies and allergy-triggered asthma.
The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.
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