Interim data from a phase IIa test of Anaptysbio Inc.'s etokimab showed a single dose of the drug improving lung function for a small group of adults with severe eosinophilic asthma by an amount that put it "in roughly the same ballpark" as Dupixent (dupilumab) and Fasenra (benralizumab), Evercore ISI analyst Josh Schimmer suggested. Anaptysbio's president and CEO, Hamza Suria, dismissed direct comparisons as unsupported by the trial's design. Meanwhile, investors, enthused by the comparison or simply encouraged by the data alone, lifted company shares (NASDAQ:ANAB) 9.9 percent higher Monday to close at $101.95.

Managers at the San Diego-based company said the interim data supported setting their sights on running a multidose, randomized phase IIb trial next year. It's intended to test etokimab in additional eosinophilic asthma patients beyond the sole 13 who received it in the phase IIa. The bigger IIb test could more fully illustrate the drug's potential for inhibiting IL-33, which Suria described during a Monday conference call as "an early and broad mediator of inflammatory response."

Asthma affects up to 358 million people worldwide, according to a Cortellis Disease Briefing, and up to 10 percent of asthma patients have severe asthma which may be uncontrolled despite the use of chronic oral corticosteroids or other drugs. People with eosinophilic asthma can suffer particularly acute symptoms, as eosinophils – a type of white blood cell – lead to inflamed airways.

The current standard of care for add-on maintenance treatment of severe, eosinophilic asthma patients is medium to high-dose inhaled corticosteroids (ICS) plus a long-acting beta2-agonist (LABA), with many patients also receiving oral corticosteroids with as-needed short-acting beta-agonists, which are typically used as rescue medications to provide quick relief of asthma symptoms.

Both cohorts of patients in Anaptysbio's study received background therapy with ICS and LABA. The company then went on to show that, at day two of treatment, those who received a single 300-mg I.V. dose of etokimab saw an 8 percent increase over placebo in forced exhaled volume in one second (FEV1) – a common measure of lung function. That improvement was sustained throughout the interim analysis period, with an 11 percent increase over placebo at day 64.

With just 25 patients enrolled in the proof-of-concept trial it "may not be predictive of results we will experience in later studies," the company allowed in a recent regulatory filing. Still, Jefferies analyst Biren Amin wrote that at least one client asked why these data should "not be compared to Dupixent phase III data in patients with baseline of high eosinophils where Dupixent reported FEV1 improvement of 15 percent over placebo." The better comparison, he offered, was phase II Dupixent data, which showed an FEV1 improvement of 8.5 percent vs. control at week four on background of ICS/LABA."

Finding separation

Further trials next year are likely to clarify how closely etokimab's character matches that of better-known drugs. But, for now, Anaptysbio's Suria sees it destined to differentiate on the basis of superior efficacy relative to antibodies that target a subset of downstream cytokines, the need for relatively infrequent administration, safety and broad applicability to atopic diseases.

Other companies advancing potential therapies for eosinophilic asthma continue to march ahead. For asthma alone, Anaptysbio had identified Roche Holding AG's Xolair (omalizumab), Glaxosmithkline plc's Nucala (mepolizumab), Teva Pharmaceutical Industries Ltd.'s Cinqair (reslizumab), Sanofi SA and Regeneron Pharmaceuticals Inc.'s Dupixent and Astrazeneca plc's Fasenra.

Anaptysbio is targeting IL-33 because of its role as a central mediator of atopic diseases, he said. "IL-33 has been of significant interest as a therapeutic target for allergic disease therapy because it has the potential to deliver a broader efficacy profile in antibodies targeting the IL-5 pathway or the IL-4, 13 receptor," he added.

Indeed, the company is already advancing etokimab for the treatment of moderate to severe atopic dermatitis and chronic rhinosinusitis with nasal polyps. Top-line data readouts from phase II trials in both indications are expected during the second half of 2019. Altogether, the company expects to report four additional phase II readouts between now and the end of 2019. The next catalyst, according to Amin, should be data of ANB-019, an IL-36 receptor antagonist, which is being tested in a small group of patients with generalized pustular psoriasis.