Cancer drug acalabrutinib shown to temporarily prevent allergic reactions to peanuts

A small study has shown that a cancer drug called acalabrutinib improves tolerance to peanuts in the short term, making it the first drug to achieve rapid-onset prevention of IgE-induced allergic reactions. 10 adults with peanut allergy were given four doses of acalabrutinib over two days. Seven were able to eat the equivalent of 16 to 20 peanuts and the remaining three were able to tolerate a smaller but still significant amount. More research is needed but the results are encouraging and relevant to other IgE-mediated allergies.

Acalabrutinib is one in a class of medications called BTK inhibitors (Bruton’s tyrosine kinase inhibitors). They work by blocking BTK, an enzyme in various immune cells that plays an essential part in IgE-mediated allergic reactions. 

This study aimed to look at the safety of these drugs and how well they work for treating peanut allergy in the short term. The adults included were highly allergic to peanuts. They were given tiny amounts of peanut at the start of the study to see if they caused a reaction, known as a food challenge, and were found to react to an average of 29 milligrams of peanut, equivalent to  1/10^th of a peanut. Six weeks later they were given four standard doses of acalabrutinib over two days, then given another food challenge.

Seven of the 10 could eat over 4,000mg of peanut without having a reaction, equivalent to 16 to 20 peanuts. This was the maximum amount tested. The remaining three participants could tolerate smaller amounts ranging from 444mg to 3,044mg. Four had side effects which were not serious.

The results showed the drug can allow for patients to eat a meaningful amount of their food allergen, and is the first treatment to achieve rapid-onset prevention of IgE-induced food reactivity. This could have real world benefits such as allowing patients to go on holiday or to support immunotherapy. The trial did not assess how long the effects of the drug would last, but previous studies suggest some markers return to baseline within a week.  

The study supports the need for larger, placebo-controlled trials to investigate safety, how well they work and at what dose. The results should also be relevant for other allergies. The authors said “Because of shared underlying mechanisms between cases of anaphylaxis, results herein are expected to be applicable for any IgE-mediated systemic allergic reaction.”

The cancer drugs are also being researched for other conditions, with promising results: “Encouragingly, next-generation BTK inhibitors that are currently in development for chronic urticaria and autoimmune diseases are more selective for BTK with fewer off-target effects, and therefore show more favorable side effect profiles.”

Read the study in J Clin Invest.