The new AAAAI podcast is about Palforzia–surprise surprise. It was recorded just three days after the introduction. Like all these podcasts the host is our friend Dr. David Stukus. Appropriately the interviewee is Dr. Andrew Bird from Dallas who contributed a piece to this website five years ago called Food Allergy Testing in the Coming Age of Prescription Immunotherapy. Dr. Bird wrote at the time, “The response from the medical community must be to ensure that patients are appropriately diagnosed and diagnostic methods are used intentionally in patients with a history supporting a role of immediate reactivity following food ingestion.” Five years later, that remains a key concern as this first-ever drug enters the market and is clearly explained, as are such issues as cost, dosing, maintenance, overall efficacy for certain patients, reactions, goals of treatment, and why patients choose to discontinue treatment. There’s also forthright discussion of the pros and cons of offering the treatment for allergists and shared decision making in choosing to start the treatment or not.
BRISBANE, Calif.–(BUSINESS WIRE)–Aimmune Therapeutics, Inc. (Nasdaq: AIMT), a biopharmaceutical company developing and commercializing treatments for potentially life-threatening food allergies, today announced that the U.S. Food and Drug Administration (FDA) approved PALFORZIA™ [Peanut (Arachis hypogaea) Allergen Powder-dnfp]. PALFORZIA is the first approved treatment for patients with peanut allergy. It is an oral immunotherapy indicated for the mitigation of allergic reactions, including anaphylaxis, that may occur with accidental exposure to peanut. PALFORZIA is approved for use in patients with a confirmed diagnosis of peanut allergy. Initial dose escalation may be administered to patients aged 4 through 17 years. Up-dosing and maintenance may be continued in patients 4 years of age and older. PALFORZIA is to be used in conjunction with a peanut-avoidant diet. PALFORZIA is not indicated for the emergency treatment of allergic reactions, including anaphylaxis.
“This is a defining moment for the peanut allergy community and for Aimmune Therapeutics, and we are excited to bring the first FDA-approved treatment for peanut allergy to patients and their families,” said Jayson Dallas, M.D., President and CEO of Aimmune Therapeutics. “Our commercial field team is ready to begin engaging with allergists to help them prepare to safely incorporate PALFORZIA into their practices and, with approval in hand, our payer team can also immediately begin work to secure formulary access to PALFORZIA. We view this approval as just the beginning for Aimmune, and it underscores our continued commitment to bringing innovative treatments to people with potentially life-threatening food allergies.”
“Not only is PALFORZIA the first approved therapy for peanut allergy, but it is the first approved therapy for any food allergy,” said Daniel Adelman, M.D., Chief Medical Officer of Aimmune Therapeutics. “We truly appreciate the efforts of the peanut allergy community who contributed to the development of PALFORZIA – including the more than 1,200 patients and their families who participated in our clinical trials, the study investigators and their staff, the advocacy community, and our dedicated employees – all of whom have helped us develop and deliver this first-of-its kind therapy.”
Peanut allergy is one of the most common food allergies in the world, affecting more than 1.6 million children and teens in the United States alone.i,ii It can be a chronic and life-long condition, and reactions to peanut can range from mild to potentially life-threatening,iii with one in five peanut-allergic patients visiting emergency rooms each year due to accidental exposures.iv
“Peanut allergy is more common now than ever before and has become a serious public health concern. The food allergy community has been eagerly awaiting an FDA-approved treatment that can help mitigate allergic reactions to peanut and, as allergists, we want nothing more than to have a treatment option to offer our patients that has demonstrated both the safety and efficacy to truly impact the lives of patients who live with peanut allergy,” said Christina Ciaccio, M.D., Associate Professor of Pediatrics and Medicine and Chief of Allergy/Immunology and Pediatric Pulmonary Medicine at the University of Chicago Medical Center and Biological Sciences. “With today’s approval of PALFORZIA, we can – for the first time – offer children and teens with peanut allergy a proven medicine that employs an established therapeutic approach.”
PALFORZIA is a complex biologic drug used with a structured dosing approach that builds on a century of oral immunotherapy (OIT) research.v With OIT, the specific allergenic proteins are ingested initially in very small quantities, followed by incrementally increasing amounts, resulting in the ability to mitigate allergic reactions to the allergen over time. PALFORZIA is a rigorously developed, pharmaceutical-grade OIT for peanut allergy with a well-defined allergen profile to assure that every dose, whether 0.5 mg (equivalent to 1/600th of a peanut) or 300 mg, has been prepared and analyzed for consistency.
The Biologics License Application (BLA) for PALFORZIA included efficacy and safety data from seven clinical studies, including the pivotal Phase 3 PALISADE and RAMSES clinical trials. In addition, data from the Phase 2 ARC001 study and the ARC002 open-label follow-on study were included, as well as data from ARC004, ARC008 and ARC011, which are ongoing studies.
PALFORZIA is available only through a Risk Evaluation and Mitigation Strategy (REMS). Requirements of the REMS include: the prescribing physician and patient must be enrolled in the REMS prior to initiation of treatment; the initial dose escalation and the first dose of each up-dosing level must be administered in a certified healthcare setting; epinephrine must always be immediately available to patients; and pharmacies/distributors must be certified with the REMS and dispense PALFORZIA only to certified healthcare settings or to patients who are enrolled in the REMS. Consistent with approved immunotherapies indicated to treat allergic conditions, the Prescribing Information for PALFORZIA contains a boxed warning.
Aimmune will provide resources to patients and families who, upon consultation with their physician, wish to seek treatment with PALFORZIA. These resources will include educational materials, a dedicated call center, a co-pay program for eligible patients, and a Patient Assistance Program to provide PALFORZIA at no cost to eligible patients.
“Peanut allergy carries an overwhelming psychosocial burden that impacts patients and their families daily – peanuts are everywhere, and the threat of a severe reaction related to an accidental peanut exposure dominates families’ daily lives,” said Lisa Gable, Chief Executive Officer, Food Allergy Research and Education (FARE). “The risk of accidental exposure is real, and we, as a community, have long awaited an option beyond avoiding peanuts alone. As one of the organizations that originally highlighted the need for an FDA-approved oral treatment approach to food allergy back in 2011, we are thrilled with today’s FDA approval of PALFORZIA as it fills a long-standing need in the treatment of peanut allergy.”
Aimmune Therapeutics was founded directly in response to a united call to action by leading stakeholders in food allergy. At an advocacy-sponsored research retreat in 2011 aimed at reaching consensus on the direction of food allergy treatment research, a group of parents of children with severe food allergies, patient advocacy organizations, leading clinical and academic physicians, representatives from government, and members of the pharmaceutical industry recognized the need for a structured approach to OIT and approved treatments. This meeting eventually led to the formation of Aimmune Therapeutics to specifically address that need.
By Dr. Paul Ehrlich
With the age of prescription therapy for food allergies rapidly approaching, it’s not too early to start figuring out what patients will prefer among the options presented. Allergists and their patients have confronted similar dilemmas before, although simple preference doesn’t solve the problem. For example, we have been offering shots for a hundred years, and no one is terribly fond of them. To many, sublingual immunotherapy (SLIT) sounds like a dream, but experience teaches us that in the real world patients don’t like them in nearly equal measure. Taking a medicine every day is burdensome, and many patients don’t like the way the medicine feels and tastes in their mouths.
Thus, it was fascinating to read about Dr. Matthew Greenhawt’s presentation to the ACAAI meeting in Houston about patient and caregiver feelings concerning two modes of therapy that are rapidly nearing availability—Palforzia oral immunotherapy (OIT) and the Viaskin “peanut patch,” also called epicutaneous immunotherapy or EPIT. A total of 200 children aged 7-11 and 206 caregivers were surveyed with questionnaires replete with emoticons to express their feelings in addition to straight answers. Compliments to Matt and his team for their imagination in assaying patient emotions as part of the package.
Unsurprisingly their greatest concerns were over the prospect of medical emergency, but they were also deeply disturbed by things like touching, tasting, and smelling peanuts. Questioned about the prospective treatments, many rejected the oral approach. Many more were drawn to the idea of the patch.
Looking at the numbers, I began to think about my own experience over many years. The two key senses—taste and smell—have figured heavily in the lives of many patients whom I first met as children, and treated on into adulthood, and in many cases treated their own children. While there was no such thing as active treatment all those years, some of them did manage to outgrow their allergies, including to peanut. I would test them for IgE and do skin prick testing and urge them to try their allergens or do an office food challenge. But for some, the chance to eat the allergen just wasn’t enough to overcome that sensory aversion, although some do arrive at some remarkable strategies over time. The key is to associate food with the pleasure it is meant to give rather than regard it as medicine.
It’s early days for food immunotherapy, but it’s not so early that we can’t start figuring in the dimension of time. Longitudinal data for some of the earliest studies show that many subjects drop out. Medication fatigue is a real thing with all chronic disease management. It’s likely to factor heavily as OIT, the patch, and other non-curative treatments hit your allergist’s office. Those early aversions and fears at the front end have their analogues on the back end.
But maybe that’s not a bad thing. In a recent talk, one of the pioneers of private practice OIT observed that patients he had treated as little kids would come to him as they reached adolescence and inform him they were quitting. He was okay with that. He had helped them deal with their allergies long enough to come of age and could make their own decisions. They could negotiate the risks for themselves. I liked hearing this.
With a range of treatment options on the horizon, the allergist’s responsibility remains the same. To understand patient and caregiver needs and fears, to provide treatment when appropriate while explaining all the risks and offering lots of encouragement, and be just as considerate and well-reasoned when rejecting a treatment. One thing is sure: all those fears and aversions covered in Matt’s study are going to be a constant. We may have seen it all before, but it’s always new to the patient.