Queues are out of the door for a Phase III trial investigating the efficacy and safety of a new oral biologic designed to desensitise people to peanut protein and protect them from experiencing life-threatening reactions when they’re accidentally exposed to it. The hope is that by 2019 in the US and 2020 in Europe, there will be an approved drug on the market to protect the 1%-2% of children with peanut allergy, 80% of whom will never grow out of it.

It’s been an unconventional road to reach the point where a licensed therapy for peanut allergy is within reach. Although treating food allergy with immunotherapy (where you start by administering very small quantities of the food and gradually build it up until the patient can tolerate a reasonable amount) is an approach that’s been around for over a century, a safe, regulated pharmaceutical product has never been developed, largely because Big Pharma hasn’t been willing to invest in an active substance – food – which cannot be patented.

What’s been happening instead is that clinics in the US and Europe have developed their own forms of oral immunotherapy using food, but as these haven’t been regulated or controlled, they have been considered too risky to become widespread.

For this reason, in 2011, a patient advocacy group, now known as Food Allergy Research & Education (FARE), called a meeting of industry experts, including the US Food and Drug Administration (FDA), during which it was made clear that the only way that oral immunotherapy for food allergy could progress to becoming a licensed product was if it went through the full rigours of drug development.

With no existing pharmaceutical company willing to take on the challenge, FARE – with the help of $12m from wealthy donors – stepped up to the plate. The Allergen Research Corporation was born, and two Phase II trials and a name change later, Aimmune Therapeutics is now well on the way to meeting its original goal: to take what is a known treatment for peanut allergy – oral immunotherapy – and make it into a licensed pharmaceutical product capable of protecting patients from the life-threatening reactions they experience when exposed to peanuts.

The CODIT approach

The key to Aimmune’s approach and what differentiates it from the unregulated immunotherapies that have come before is characterisation. “Our approach is called CODIT – characterised oral desensitisation immunotherapy,” explains Sue Barrowcliffe, Aimmune’s general manager for Europe. “Not only do we have to characterise the quality of the product, i.e. precisely control the amount of key allergens that are delivered, but we also have to characterise how it should be done from a clinical perspective.”

“Participants were started on a dosage of 3mg of peanut protein and gradually up-dosed.”

In double-blind, placebo-controlled Phase II clinical trials, participants were started on a dosage of 3mg of peanut protein and gradually up-dosed to 300mg (equivalent to around one peanut) over a period of approximately six months. Up-dosings took place every two weeks and following completion of the up-dosing protocol, patients continued to take an ongoing, daily maintenance dose of 300mg for three months.

Results were extremely promising, with 90% of patients who completed the study period being successfully desensitised to a single 600mg dose of peanut protein (the equivalent of two peanuts). Around 60% could eat three to four peanuts. “Although they’re maintained on a single dose of 300mg, their ability to tolerate peanut continues to improve,” Barrowcliffe says.

Expanding the data

At present, two Phase III trials are underway – a 550-patient global study PALISADE, which will conclude later this year and a 160-patient European trial ARTEMIS, which has just enrolled its first patients. The latter aims to expand the data available on the efficacy profile of Aimmune’s product, AR101, by exploring a higher level of protection, after a shorter treatment period, in a broader group of patients.

“In ARTEMIS, you can get into the study if you react to less than 300mg, rather than 100mg [the cut-off point for previous trials] because firstly, people’s sensitivity varies depending on the day and secondly, just because you have a higher level of sensitivity, it doesn’t mean you can’t have a severe reaction,” Barrowcliffe explains.

“We’ve also decreased the length of the study from 12 months to 9 months to see how quickly people reach good levels of protection and we’ve moved the primary efficacy point from 600mg to 1g because our extension of our original phase II trial gives us the confidence that a lot of patients can reach that level.”

While PALISADE enrolled adults and children, ARTEMIS will only enrol patients aged 4-17. If both trials are successful, the next step will be to seek marketing authorisation from both the FDA and the European Medicines Agency (EMA), with approval anticipated in late 2019 in the US and 2020 in Europe.

Overwhelming demand

There’s been no shortage of patients keen to enrol in Aimmune’s ground-breaking studies, which together constitute the largest oral immunotherapy clinical trial programme conducted to date in peanut allergy. PALISADE was expanded from a 500-patient study to a 550-patient trial because of overwhelming demand and the first centre to start enrolling patients for ARTEMIS – Evelina London Children’s Hospital at Guy’s & St Thomas’ NHS Foundation Trust – already has a long waiting list.

“We were set up by patients and our mission is to help those patients with food allergy.”

This clearly underlines both the need for an effective licensed treatment for peanut allergy, which in the US and Europe affects approximately six million people, including more than two million children, and the commitment families have to improving their children’s quality of life.

Barrowcliffe explains: “This isn’t necessarily an easy treatment to go through – you have to subject yourself or your child to a food challenge at the beginning of the study, which can be quite scary, and then go back every two weeks to the hospital to have your dose increased for around five months.

“We had a young child in one of our centres who had a really bad reaction in the initial food challenge and our investigator thought the parents would decide not to proceed. But they were absolutely adamant. Until you talk to them, you don’t really understand the fear they live with and their desire to protect their children.”

Although peanut is serving as the CODIT platform’s trailblazer, because of the sheer number of people with peanut allergy, AR101 is only the beginning. Aimmune also hopes to expand its approach to tree nuts and egg, among other allergens, as well as joining the hunt for a cure.

“We were set up by patients and our mission is to help those patients with food allergy by giving them the protection they need to improve their quality of life. Of course, we’d love to find cures and there is some evidence that immunotherapy in very young children can reverse the immune system issues that results in the allergy. This is an area we hope to look at. If we can’t do that, however, AR101 is an excellent step,” concludes Barrowcliffe.