Eosinophilic Disorder Therapy AK002 Shows Success in Phase 1

Gerald Gleich, MD

The makers of a new therapy aimed at depleting eosinophils say their phase 1 study has been a success.

Allakos Inc., a California-based biopharmaceutical firm, announced the results last month at the Joint Congress of the American Academy of Allergy Asthma and Immunology and the World Allergy Organization, in Orlando, Florida.

The therapy, AK002, is a humanized Siglec-8 monoclonal antibody that targets eosinophils in the blood. Eosinophils and mast cells are believed to impact the body’s immune system response and are believed to play a role in the pathology of a number of diseases, ranging from gastrointestinal diseases to atopic dermatitis and asthma.

In the double-blind, placebo-controlled study, healthy patients were given AK002 or placebo intravenously in 7 different dosing groups. The therapy achieved its primary endpoint for this study, proving to be safe and well-tolerated. Only mild to moderate infusion reactions were reported, but they resolved quickly, according to the company.

However, the therapy also showed that eosinophils were completely depleted in the blood 1 hour after dosing, regardless of the dosing level. In the 2 highest dosing groups, eosinophil depletion continued for 28 and 84 days, generally increasing with increases in dosing.

AK002 is being investigated as a treatment for eosinophilic gastritis, with or without eosinophilic gastroenteritis. There are currently no approved therapies for those conditions. However, there are therapies for other eosinophilic disorders, such as eosinophilic asthma. Those therapies take a number of different approaches to attack this category of disorders.

Eosinophils help fight off infections and usually make up less than 5% of the white blood cells in the body. Eosinophil levels can become elevated, sometimes due to infections, allergies, or certain gastrointestinal disorders. In some cases, however, eosinophils are elevated and there’s no apparent cause. According to the American Partnership for Eosinophilic Disorders (APFED), such patients may have an eosinophilic disorder.

Many eosinophilic asthma patients respond well to traditional asthma therapies, but a trio of biologics have been developed and approved specifically for eosinophilic asthma. Two of the 3—Mepolizumab and Reslizumab—work by limiting the bone marrow’s ability to produce eosinophils.

Those 2 biologics were approved within the past 2 years. Gerald Gleich, MD, an eosinophil expert at the University of Utah and a member of the board of directors for APFED, told MD Magazine it’s too early to know what unmet need remains in the eosinophilic asthma community because the unmet needs are “evolving and still being determined.”

“In time, we will have a better understanding as to the long-term effectiveness of these treatments, and how patients are responding to them,” he said.

Gleich added that it will also take time to fully understand the long-term effect of the eosinophil-depletion strategy, in particular. Bradley A. Becker, MD, a professor of allergy and immunology at the University of St. Louis, said an area where early intervention appears to make a difference is with allergen immunotherapy shots.

"There is also data showing the use of allergen immunotherapy [such as allergy shots] in pediatric patients with allergic rhinitis allergic to 1 inhalant allergen can prevent the development of multiple allergies," Becker said. "There is also data the use of allergy shots in children with allergic rhinitis can prevent the development of asthma."

Gleich noted that not all patients will respond favorably to any particular treatment, though he said thus far, the approved eosinophilic asthma therapies appear to be very well tolerated. The major drawback, he said, is the high cost of biologic medications.