Has science cracked the peanut allergy?

Amid the rise in food allergies, two new treatments are on the verge of approval. David Crow on how they work and why our food has turned against us.

The number of people afflicted with food allergies has exploded since the start of the 20th century, when two French scientists, Charles Richet and Paul Portier, described the first case of fatal anaphylactic shock. When the pair collected a Nobel Prize for their work in 1913, the illness was still a curiosity rather than a public health issue. But today roughly 15 million Americans and 17 million Europeans suffer from food allergies, with many of the most serious cases afflicting children. Among the biggest factors behind this dramatic rise has been the soaring prevalence of peanut allergy, which accounts for more than a quarter of all childhood cases. Three million people in the US have allergies to peanuts, tree nuts or both. About 2 per cent of American children are now allergic to peanuts, a figure that has more than quadrupled since 1997. The number of fatal reactions is small, with fewer than 100 cases usually recorded each year, but the fear among parents remains high. Almost all the deaths have been people who knew they had the illness but ended up ingesting nuts by mistake. More and more schools are going “nut free”, while some food producers are cutting peanuts out of all their products, but scientists warn that widespread abstinence will only exacerbate matters. A better solution would be to develop a treatment that would protect sufferers in the case of accidental exposure. At 105, Dr Bill Frankland has more than earned his status as the “grandfather of allergy”. The evening we speak, the British immunologist is about to rush out but he still has time to regale me with stories from his long career, including the time in 1979 when he treated Saddam Hussein, the late Iraqi dictator. “People have been eating eggs and peanuts and dairy for years, so why is this happening now?” he asks. “There are so many reasons, it is multifactorial: general pollution, diesel fumes and so on, but also because allergy is now more recognised as a chronic disease, so doctors are very interested in it. “One thing you mustn’t put the increase down to is genes,” he adds. Although some people are more genetically predisposed to developing food allergies, the proportion has not changed over time, he says, meaning environmental factors must be to blame. “Now we’re very interested in the beginning of a baby’s life — what they’re eating and what they’re breathing in, and we need to do more research on that.”

Frankland is puzzled as to why it has taken so long to develop treatments that might protect peanut allergy sufferers. He recalls that, 60 years ago, he successfully treated people with severe fish, egg and milk allergies by admitting them to hospital and giving them controlled injections containing the very substances that could kill them. “They were in for 12 or 13 days and they went out cured,” he says. Progress in tackling peanuts has been much slower, in part because even tiny amounts can prove fatal. Researchers experimented with peanut injections in the early 1990s but the results were not encouraging. Although some patients were successfully desensitised, a significant number had severe reactions. One study was shut down after a participant died of anaphylactic shock. In 2009, a team of scientists led by Dr Wesley Burks, then a paediatrician at Duke University in North Carolina, published a small trial that is now widely hailed as a breakthrough. “The concept was to give someone something in a very small amount and increase it over time,” Burks recalls. “The desensitisation started with a thousandth of a peanut and we increased that. Then, all of a sudden, we were giving the children a peanut every day and they were not having serious reactions.” After 10 months, some could ingest as many as 15 peanuts a day, giving them a meaningful buffer in the event of accidental exposure. This pioneering treatment gave birth to a cottage industry in the US: some allergists now offer their own home-brew versions of Burks’ “oral immunotherapy” in their practices. But the majority do not want to offer a makeshift solution, for fear they would be held liable if something went wrong. Burks’ research also caught the attention of advocacy group Food Allergy Research and Education (FARE), which tried to persuade several large drugmakers to turn it into an approved drug. Big Pharma was unmoved, believing it would be impossible to patent a medicine that was essentially a ground-up peanut. So FARE’s leaders decided to back efforts to start a new company. They secured $12m of seed funding from wealthy investors, including David Bunning, the Citadel financier whose children suffer from severe food allergies. The company, now known as Aimmune, went on to raise a further $414m. Aimmune has used the cash to develop a low-dose version of Burks’ therapy that can be professionally manufactured at scale: a capsule containing pharmaceutical-grade peanut protein, which is snapped open and sprinkled over an appropriate food, such as chocolate pudding. After more than four years of clinical trials, this drug, codenamed AR101, is in the final stages of testing, with results due either at the end of this year or in early 2018. In small studies, patients were able to tolerate the equivalent of between two and three peanuts after nine months of treatment, and research suggests this will increase over time. Three peanuts might not sound a lot but it would be sufficient to protect a person against accidental ingestion. It would also probably convince US regulators to approve the medicine for children aged between four and 17. Shares in Aimmune have appreciated by around a third over the past 12 months, giving the company a market value of almost $1bn, as investors bet that the Food and Drug Administration and European regulators will give a green light to the medicine in 2019. Analysts at Credit Suisse predict the drug will generate sales that will crest at $1.4bn a year in 2024.

Success is not guaranteed. The history of drug development is littered with examples of medicines that looked like a sure thing but went on to fail. Nor is treatment with AR101 a panacea. It takes a long time, involves regular trips to an allergist and is quite unpleasant. “It’s not for everyone, because there are side effects associated with the treatment and you have to invest time and effort in repeated visits to the doctor,” says Stephen Dilly, chief executive of Aimmune and a former vice-president of pharmaceutical company SmithKline Beecham. “The utility of our treatment tends towards the super-sensitive patient that is more likely to have a life-threatening reaction if they get exposed.” The first visit takes three hours, during which the doctors slowly increase the dose of AR101 until they work out the maximum tolerable amount. The child must then return every fortnight to see whether he or she is ready to progress to a larger pill. The vast majority will experience nasty reactions, such as hives or stomach aches, and the process typically takes between 24 and 26 weeks before the patient can go on a regular maintenance capsule. Although the company says it is not a treatment for life, it is still unclear how long a patient might have to take the drug. Aimmune has ties to the food industry, which has a vested interest in finding treatments for allergies. Its largest investor is Nestlé, which acquired a 15 per cent stake for $145m in November 2016. The success of AR101 and other treatments could help protect the food giant’s core business, which sells many products containing peanuts and other allergens. The peanut trade also has a lot riding on the success of these treatments, with one of the largest companies, Golden Peanut, agreeing to provide the protein for the capsules under an exclusive 10-year deal. Dilly says it is more than just a commercial arrangement. “They’re very interested in being seen to be helping us,” he says. “Because they’ve gone from being good old peanut farmers in Georgia to being the people that produce stuff that kills people.” For Bob Parker, president of the National Peanut Board, the reputational hit hurts. He has spent a lifetime in the industry and grew up in the heart of peanut country in Georgia, where, at the age of six, he was selling bags of boiled nuts at the side of the road. Today, everyone he meets asks him the same two questions. Has he met Jimmy Carter, the former US president and world’s most famous peanut farmer? “Many times. He’s a fine man.” And how is the industry coping with a spike in peanut allergy? “It’s the single largest barrier to consumption.”

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