Stanford researchers pursue AnaptysBio's embattled IL-33 drug in peanut allergy

Peanuts in shell
An injection of AnaptysBio’s anti-IL-33 antibody etokimab could help prevent peanut allergies, Stanford University scientists found in a small clinical study. (Pixabay/riteshman)

Last week, AnaptysBio’s stock plunged 70% on news that one of its most advanced projects, the drug etokimab to treat eczema, failed a phase 2b trial. In fact, patients in the treatment group fared even worse than those taking a placebo after 16 weeks of treatment.

But some academic researchers are still interested in the drug's potential to tamp down inflammation. Among them are scientists at Stanford University who have come out with new data suggesting that one injection of the antibody drug could help prevent peanut allergies. The results are intriguing enough to pursue further clinical trials in peanut allergy, the study’s senior author, Kari Nadeau, M.D., Ph.D., told FierceBiotechResearch.

In a study with 20 people with severe peanut allergies, 11 of 15 patients (73%) who were taking etokimab could tolerate 275 mg of peanut protein, or about one nut’s worth, after two weeks, while none of the patients on placebo could do so. At day 45, 57% participants in the etokimab arm passed the food challenge. The results were published in the journal JCI Insight.

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A common strategy for researchers developing remedies for peanut allergy is to desensitize patients by giving them gradually increasing doses of the allergen. This approach usually requires a long preparation period to reach tolerance. For example, Aimmune’s AR101, which recently won backing from an independent FDA expert panel for approval in peanut allergy, went through a 22-week dose escalation phase in a late-stage trial. Treatment with etokimab could be much simpler, Nadeau believes, because desensitization is not required. 

Etokimab is designed to block interleukin-33 (IL-33), an immune-signaling molecule. In peanut allergy, the body overreacts to peanuts as IL-33 activates an antibody called immunoglobin E. These antibodies cause allergic response such as mouth itchiness, hives, breathing difficulties and potentially fatal anaphylactic shock.

RELATED: AnaptysBio's IL-33 antibody stumbles in midphase eczema trial

AnaptysBio released preliminary results from the peanut allergy study last year, which hinted at the effectiveness of a single injection. But after evaluating the commercial prospects of etokimab in peanut allergy, AnaptysBio decided to “deprioritize further company-sponsored clinical development” of the IL-33 inhibitor for the indication, it said at the time. Instead, it said it would consider supporting investigator-sponsored trials.

Then came the surprise disappointment in eczema. Now, AnaptysBio is postponing a phase 2b study in eosinophilic asthma until it has full data from the eczema study. Meanwhile, an ongoing phase 2 is testing the drug in chronic rhinosinusitis with nasal polyps.

Some academic scientists who remain interested in etokimab have been designing studies to investigate how the drug works to control inflammation. A team at the University of Oxford, for example, recently found that etokimab's link to a drop in white blood cells called neutrophils—which lead the body’s immune response—could exert its effect in eczema.

RELATED: U.K. team sheds light on how AnaptysBio's anti-IL-33 eczema drug tamps down inflammation

The competition in peanut allergy is heating up. DBV Technologies is working on an AR101 rival called Viaskin. And Roche’s asthma drug Xolair—which, like those drugs, targets IgE—bagged an FDA breakthrough designation last year as a treatment for food allergies including for peanuts, milk and eggs.

Because etokimab does not rely on a specific allergen to induce tolerance, it might eventually find a broader audience, the Stanford researchers believe. “By inhibiting IL-33, we potentially inhibit features of all allergies, which is promising,” Nadeau said.

Now that AnaptysBio has backed out of etokimab’s development in peanut allergy, researchers will likely pursue a larger trial to determine the best dosing regimen, even though it's “hard to say when and who will run it,” Nadeau said. Scientists will also look for biomarkers that can help identify the best candidates for the antibody drug. “One can use ST2, IL-33, soluble ST2, IL-25 , TSLP and other downstream markers, too most likely,” Nadeau told FierceBiotechResearch. “Our results show certain cytokine profiles, which are intriguing.”

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