Allergy Therapeutics’ Birch Allergy Jab Has a Puzzling Failure

UK-based Allergy Therapeutics markets three allergy “jabs” for tree pollen, dust mites, and grass pollen. Later this year it is planning results from a Phase I trial of a dust mite vaccine. But the company’s results from its trial for a birch pollen vaccine are a bit puzzling—the vaccine flunked the trial, but appeared to show positive results.

The vaccine is called Pollinex Quattro Birch (B301). The Phase III clinical trial of B301, an adjuvanted birch allergoid product, did not show a statistically significant difference between the drug arm and placebo arms for the primary endpoint of combined symptom medication score averaged over the peak birch pollen season. The safety and tolerability profiles were positive and consistent with previous trials.

The secondary endpoints, analyses of immunoglobulin IgG and IgG4 and other immunoglobulin markers, showed highly statistically significant differences between the vaccine and placebo arms. This suggests a strong and sustained immune response.

“We are surprised by the result, given the strong immune response suggested by the increased immunoglobulin markers in the treatment arm and the substantial symptom improvement we had observed in earlier trials,” stated Manuel Llobet, Allergy Therapeutics’ chief executive officer. “We will now undertake a comprehensive review of the full dataset to determine our path forward with the investigational product. As a science-driven company we are conscious at Allergy Therapeutics of the challenges regarding subjective measures in allergy field studies. We are committed to overcoming these challenges and bringing this new product to market.”

In previous Phase II trials, the birch vaccine showed a highly statistically significant reduction of 32 percent in allergic symptoms. The B301 trial was a multi-center, double-blind, placebo-controlled trial to test its efficacy in birch-pollen induced seasonal allergic rhinitis. The study was conducted in Germany, Poland, Austria and Sweden with 582 patients at 59 centers.

Company shares plunged 40 percent in early trading after the news. Despite having several products on the market, the company had a previous five-year clinical hold in the U.S. starting in 2007 for its Pollinex Quattro Grass vaccine after a trial participant reported numbness and weakness. That clinical hold was lifted in 2012 and eventually the company raised $20 million to move the vaccine through late-stage development. But a year later, it had poor trial results in a mid-stage dose-ranging study.

After some retooling, the company’s grass allergy vaccine met its primary endpoint in May 2018.

But now the company must be wondering if they’re having déjà vu with its birch pollen vaccine. Evaluating symptoms in allergies can be subjective, depending as they do on patient reports. For example, two years ago, another UK company, Circassia, discontinued its entire allergy pipeline after its immunotherapy for allergies to house cats did not show improvement over placebo in a Phase III trial. And a French company, DBV Technologies, also had a Phase III failure for its peanut allergy therapy but has since collected more clinical data to resubmit an application to the FDA.

Allergy Therapeutics indicates it plans to analyze the data further to see if it can determine the reasons for the inconsistencies.