乌鸦传媒

This article is a collaboration between 乌鸦传媒 and:

SAN DIEGO -- A novel first-in-class biologic agent targeting allergic inflammation appeared promising for allergen-induced asthma in a phase Ib trial.

AMG 157, an anti-thymic stromal lymphopoietin (TSLP) humanized monoclonal antibody, reduced most measures of early and late asthmatic responses in response to allergen challenge, , of McMaster University in Hamilton, Ontario, and colleagues found.

(3 to 7 hours after challenge) halfway through treatment at 1.5 months, and by 45.9% less than with placebo at the end of the 3 months of treatment (P=0.09 and P=0.02, respectively).

Airway inflammation markers -- blood and sputum eosinophils before and after the allergen challenge, and the fraction of exhaled nitric oxide -- also lessened with AMG 157, the group reported here at the American Thoracic Society meeting and simultaneously online in the New England Journal of Medicine.

"The magnitude of the effect of this new kid on the asthma treatment block was sizable -- similar to what may be achieved in the same clinical-research model by blocking established asthma mediators such as the cysteinyl leukotrienes," , of the Karolinska Institutet in Stockholm, wrote in an editorial accompanying the paper.

However, it's not really clear why the drug works.

TSLP probably isn't directly involved in response to the actual allergen challenge, and it doesn't contract airway smooth muscle, Dahlén noted. Indirect inhibition of downstream pathway is more likely, supported by the reductions in eosinophils in induced sputum and the level of nitric oxide in exhaled air.

Despite the positive early-phase findings, "it is an open question as to whether this strategy will be successful in the treatment of patients with asthma," he concluded. "We will first have to unravel the biologic mechanisms involved in this unexpected effect of AMG 157 and show why TSLP signaling allows airways to narrow too easily, too much, and too often."

The researchers noted that cutting allergen-induced airway responses in allergic asthma "has been associated with effective asthma treatments, even for patients with non-allergic disease."

Their trial included 31 patients with mild allergic asthma randomized to double-blind treatment with three monthly doses of AMG 157 (700 mg) or placebo intravenously. Other controller medications weren't allowed, with the exception of rescue treatment with short-acting inhaled beta-agonists less than 2 days a week.

The drug was associated with 15 adverse events compared with 12 in the placebo group, but no changes in laboratory values, temperature, blood pressure, pulse, or respiration. The only case of antibodies against AMG 157 was in the placebo group on day 169.

No serious adverse events occurred in the trial.

A second phase IIb trial with a first-in-class oral agent for allergic asthma, which turned up negative results, was reported at a late-breaking clinical trial session at the conference.

CYT003, "an immune modulator postulated to inhibit the T cell mediated airway inflammation via activation of toll-like receptor 9," wasn't any better than placebo at any of the three doses tested for the primary endpoint of asthma control at 12 weeks, , of the University of South Florida in Tampa, and colleagues found.

The trial included 365 adults with moderate to severe allergic asthma not under control with standard inhaled corticosteroid therapy (88% were also on a long-acting beta-agonist).

Secondary endpoints for FEV₁ and asthma-related quality of life likewise showed no effect from the novel agent.

It's possible the trial was done in the wrong population, as many immune response modifiers only show benefit in certain asthma phenotypes, Casale told attendees.

The agent showed signals that might indicate it's effective in steroid-naive patients with the T乌鸦传媒-hi phenotype, but the drug developer, Cytos, isn't pursuing the drug further for asthma and is .