The incidence of asthma has grown steadily over the past decade and in the U.S. it is estimated that more than 22 million people have asthma, with asthma-related hospitalizations exceeding 400,000 per year, according to the Centers for Disease Control and Prevention. Worldwide, roughly 242 million people are believed to suffer from asthma, with an estimated 5 percent unable to achieve symptom control on existing therapies. It is not surprising then that the pipeline for new therapies to treat this condition is expanding and a number of promising biological compounds have progressed into late stage testing and onto the market. (See Asthma Trials by Phase, below.)
Among them is Dupixent (dupilumab), which targets both IL-4 and IL-13 signaling via the shared alpha chain of their respective receptors, being developed by Regeneron Pharmaceuticals Inc., of Tarrytown, N.Y., and Sanofi SA, of Paris. Positive results from an interim analysis of a pivotal phase IIb study of dupilumab in adult patients with moderate-to-severe asthma, who are uncontrolled despite treatment with inhaled corticosteroids and long-acting beta agonists (ICS/LABA) were reported last year. The study met its primary endpoint of improving lung function in asthma patients with high blood eosinophil counts. These high counts are thought to be a marker for patients more likely to have "atopic" or "allergic" asthma the companies said.
Based on their discussions with the FDA, the study may be considered one of two pivotal efficacy studies required for a potential dupilumab biologics license application (BLA) in asthma.
A phase III trial of dupilumab in patients with uncontrolled persistent asthma is ongoing, which will serve as the second required pivotal efficacy study. It will evaluate two doses of dupilumab, 200 mg and 300 mg, subcutaneously administered every other week. This LIBERTY QUEST study with 1,638 asthma patients is fully enrolled and data is expected to read out next year to enable a BLA submission.
biological respiratory drugs
The companies are competing in the race for a slice of the predicted multibillion dollar market for biological respiratory drugs. First to market was Glaxosmithkline plc's Nucala (mepolizumab), anti-IL-5 monoclonal antibody, which received the green light from the FDA late last year as an add-on maintenance therapy for patients who have a history of severe asthma attacks despite being on treatment and who have an eosinophilic phenotype. (See BioWorld Today, Nov. 6, 2015.)
In July GSK added a second cytokine-targeting antibody to its respiratory disease portfolio by in-licensing Johnson & Johnson's CNTO 7160, a phase I antibody that targets the interleukin-33 (IL-33) receptor. The deal is estimated to be worth up to £175 million (US$229 million) factoring in up-front payment plus milestones covering development and first commercial sales. J&J would also gain tiered sales royalties, should the product gain approval, plus additional payments tied to its sales performance. (See BioWorld Today, July 28, 2016.)
The transaction means that GSK is going head-to-head with Genentech, a unit of Basel, Switzerland-based Roche Holding AG, which in-licensed another phase I anti-IL-33 antibody, AMG 282 from Amgen Inc. in January.
Anaptys Bio Inc., of San Diego, moved another IL-33-targeting antibody, ANB020, into a phase I trial in March. Pending full results from the trial, the company plans to develop the compound in patients with atopic dermatitis, peanut allergy and asthma.
The Nucala approval was quickly followed by Teva Pharmaceutical Industries Ltd.'s IL-5 antagonist, Cinqair (reslizumab), which gained FDA approval in March for use with other asthma medicines for the maintenance treatment of severe asthma in patients aged 18 years and older.
The safety and efficacy of Cinqair were established in four double-blind, randomized, placebo-controlled trials in patients with severe asthma on currently available therapies. Cinqair or a placebo was administered to patients every four weeks as an add-on asthma treatment. Compared with placebo, patients with severe asthma receiving Cinqair had fewer asthma attacks, and a longer time to the first attack.
Astrazeneca plc, which is also seeking to position their first biologic respiratory medicine, an IL-5 antagonist, as a key differentiator in the space, reported full data from the pivotal phase III trials of benralizumab at the European Respiratory Society (ERS) meeting in London. (See BioWorld Today, Sept. 7, 2016.)
SIROCCO and CALIMA evaluated the effect of two dosing regimens of benralizumab 30 mg, administered in four- and eight-week regimens as add-on therapy to standard of care, including high-dosage inhaled corticosteroids and long-acting beta 2 agonists. Both studies met their primary and key secondary endpoints by reducing exacerbations and improving lung function and symptoms in severe asthma patients with an eosinophilic phenotype, positioning the anti-eosinophil monoclonal antibody (MAb) for regulatory filings in the U.S. and Europe this year.
Benralizumab directly binds to the receptors on eosinophils, making them visible to the body's immune system, where natural killer cells then bind to the eosinophils and cause programmed cell death, efficiently removing them.
The company's initial focus on individuals with severe asthma represents a lucrative target market of up to 5 million patients, or up to 10 percent of those with asthma in major global markets, Cortellis Competitive Intelligence estimates the five-year consensus sales forecast to be approximately $486 million.
A protein secreted by parasitic hookworms may one day add another treatment for asthma patients. An Australian study has identified that this protein suppresses asthma in mice, with in vitro tests on cells from asthmatics indicating that the protein is a promising candidate for development of new anti-inflammatory treatments.
The study was conducted by Australian Institute of Tropical Health and Medicine (AITHM) researchers at James Cook University (JCU) in Cairns, Australia, and published in the Oct. 26, 2016, edition of Science Translational Medicine. (See BioWorld Today, Nov. 2, 2016.)
A recombinant form of the protein, called AIP-2, was also tested in vitro on human cells from people allergic to dust mites.
In May, San Francisco-based Tunitas Therapeutics Inc. presented preclinical data at the American Thoracic Society meeting demonstrating that epsi-gam significantly improves pulmonary function and reduces inflammation in an animal model of dust mite allergic asthma. Epsi-gam is a bifunctional human fusion protein which links the IgE receptor with an inhibitory receptor on mast cells, basophils and IgE-producing B cells. The company expects top-line results from a phase I study this year.