On July 11, my 10-year-old son ate a peanut. This is hardly a noteworthy event for most kids, but it could be life-changing for him. Unlike the other times Ian has eaten something that contained peanut, this time we weren’t fumbling for an epinephrine auto-injector while speeding to the emergency room. Instead, we sat calmly in our allergist’s office and watched cartoons.
Ian is one of nearly 6 million children in the US who has a life-threatening food allergy (that works out to about two children in every classroom).1 Since the beginning of the year, we have been participating in an oral-immunotherapy (OIT) program, which desensitizes patients to allergens by incrementally increasing their exposure. The goal is to decrease risk related to the accidental exposure of an allergen. OIT for peanut allergies has been available for more than a decade, but just a small percentage of allergists offer it, according to the advocacy group Food Allergy Research & Education (FARE).
OIT has not been approved by the Food and Drug Administration (FDA). It is not a cure and it requires daily maintenance doses even after the nearly year-long program concludes. Protocols can vary by allergist, and outcome data typically aren’t published. This can make it difficult to quantify results. Moreover, people who have had a past reaction to peanuts often don’t like the taste, and taking a daily maintenance dose demands a strong commitment, says allergist James Baker, M.D., FARE’s chief medical officer. Moreover, the therapy often isn’t covered by health insurance.
RWE can help shape clinical trials
Biopharmaceutical companies are increasingly using real world evidence (RWE) to optimize the design of clinical trials, according to Deloitte’s second annual RWE benchmarking survey report. RWE refers to insights generated from data gathered from a variety of sources outside of randomized controlled clinical trials. Deloitte’s report is based on survey responses and interviews with 20 executives from global life sciences organizations.
Between 1997 and 2008, the prevalence of peanut and tree-nut allergies appears to have tripled among US children, according to the Centers for Disease Control and Prevention. Rather than trying to develop a cure for these food allergies, some biopharmaceutical companies are using RWE to develop therapies that can reduce the risk of accidental exposure.
As of March, nearly 20 peanut allergy therapeutics were in various stages of development.2 At least two biopharmaceutical companies intend to seek FDA approval for peanut desensitization treatments this year. Both companies see value in RWE:
- California-based Aimmune Therapeutics was founded on RWE and the promise of OIT, spokesperson Alison Marquiss tells me. FARE, academics, and government agencies all had input into the company and its mission of standardizing the treatment to make it widely available. As the basis for its clinical trials, Aimmune licensed data from three universities that were conducting OIT trials for peanut allergies. The academic trials provided efficacy and safety information, but also offered real-world insight into the practicality of what many patients were willing to do. Marquiss says Aimmune recently concluded a successful large-scale, late-stage trial, and a subsequent trial, which used RWE to select study participants and to determine endpoints for the trial. By the end of the year, Aimmune expects to submit a Biologics License Application to FDA for its OIT therapy.
- DBV Technologies, a French biopharmaceutical company, has developed an immunotherapy patch to desensitize patients to peanuts by “activating the immune system through the skin,” according to the company’s website. Last fall, the company announced that results of a late-stage clinical trial fell short of expectations. But early this year, the company received written permission to seek FDA approval. DBV relied on RWE to select participants for its (REAL Life Use and Safety of Epicutaneous immunotherapy) REALISE clinical trial. Patients in the study were chosen based on medical history (e.g., skin tests and blood tests) and past reactions to peanut, rather than on the results of a food challenge,” says Todd Green, M.D., an allergist who is DBV’s vice president for North America medical affairs. “REALISE was designed to mimic the real world.” Food challenges, he notes, can be risky for the patient and time consuming for the allergist.
Another European biopharmaceutical company has an injectable peanut-allergy vaccine in preclinical testing, according to the company’s website. And at least two biologics for asthma are being considered for the treatment of food allergies, according to FARE.
If a commercial therapy for peanut allergies were to become available, other biopharma companies might start to see food allergies as a potential growth area. This could lead to a deeper understanding of biological mechanisms related such allergies, which could lead to better tests and more innovation. Marquiss says other biotech organizations are looking into how they can add on to existing desensitization therapies to potentially make them effective.
RWE could help close ‘knowledge gaps’
Professional medical organizations don’t sanction the OIT approach because there is too much variation in protocols. Nearly 75 percent of allergists who do not offer OIT say they are awaiting FDA approval before making a decision, according to results of 2015 survey of American Academy of Allergy, Asthma & Immunology (AAAAI) members. If it isn’t cost prohibitive, my son’s allergist says he would consider moving to a commercial OIT protocol if one became available.
Immunotherapeutic programs such as OIT are not without risks. A 2014 paper from the AAAAI concluded that more research is needed to determine “knowledge gaps” such as optimal dose, duration, maintenance regimen, and long-term outcomes.3 RWE and real-world data might be helping physicians and biopharma companies close some of those gaps.
Along with the threat of accidentally being exposed to an allergen, some kids suffer from anxiety about unfamiliar foods.4 Ian generally won’t eat anything outside of home unless he can read the label (even if I read the label first). Once he graduates from the program, he won’t have to be hyper-vigilant about what he eats. He won’t have to bring his own safe slice of cake to birthday parties. However, he will need to eat some peanuts every day to maintain his resistance, and he won’t be able to throw away his epinephrine injector.
While daily maintenance is one drawback to Ian’s OIT therapy, there are worse things than having to eat a peanut-butter cookie or peanut-filled piece of candy every day to avoid an unexpected trip to the emergency room. Even if OIT doesn’t work for Ian in the long-term, I am hopeful RWE will help allergists and biopharma companies further reduce the threat of food allergies.
1 Food Allergy Research & Education/ Facts and Statistics: https://www.foodallergy.org/life-with-food-allergies/food-allergy-101/facts-and-statistics
2 P&S Market Research, March, 22, 2018: https://globenewswire.com/news-release/2018/03/22/1444145/0/en/Peanut-Allergy-Therapeutics-Pipeline-Witnessing-Significant-Growth-due-to-Rise-in-the-Number-of-Patents-Approvals-P-S-Market-Research.html
3 American Academy of Allergy, Asthma & Immunology: https://www.aaaai.org/Aaaai/media/MediaLibrary/PDF%20Documents/Practice%20and%20Parameters/Jan-2015-Greenhawt-et-al-JACI-In-Practice-article-Allergist-Reported-Trends-in-the-Practice-of-Food-Allergen-Oral-Immunotherapy.pdf
4 Columbia University’s Mailman School of Public Health and Albert Einstein College of Medicine, June 29, 2017: https://www.mailman.columbia.edu/public-health-now/news/researchers-find-link-between-food-allergies-and-childhood-anxiety; http://ir.aimmune.com/news-releases/news-release-details/aimmune-therapeutics-announces-new-pan-european-study-showing