Tagged Clinical Trials

Will I Always Face The Threat Of A Peanut-Laden Kiss Of Death?

Whenever I see a report touting possible new peanut allergy treatments, I devour it. I can’t help it. It’s an occupational hazard for any health journalist whose reporting specialty and medical history intertwine.

I write about the business of health care, focusing on how consumers interact with the system — what we pay, what we get and why American care costs so much. But in this particular instance, I have another kind of authority: 26 years of life-threatening allergies to nuts and peanuts.

So last month, when California-based Aimmune Therapeutics sparked optimistic headlines after releasing clinical trial results that its allergy product, AR101, would reduce the risks linked to an accidental exposure to peanuts, I received the usual wave of questions from friends, co-workers and my parents: Would you try it? Could this help?

Aimmune is just one company eyeing the prize. Childhood peanut allergy diagnoses increased more than 20 percent in the United States from 2010 to 2017. The global market for relief is worth as much as $2 billion. The French drugmaker DBV Technologies is also working to commercialize a peanut allergy patch. Other companies, including industry giant Sanofi, are following their lead.

If any one of them succeeds, it could change my life.

My friends call nuts “Shefali poison.” My allergies first surfaced when, as a 15-month-old, I picked Thai noodles off an aunt’s plate and developed hives on my face, and then a few months later when I tasted my mom’s kaju barfi – an Indian dessert with cashews – and ended up in the hospital. Nobody in my family had ever heard of peanut allergies.

I’ve carried epinephrine since I was 7 years old. My friends are trained to inject it in my leg, the standard procedure for an emergency allergen exposure. though I luckily haven’t had to take a shot of it since I was 4. (Another child in my Montessori class had a peanut butter sandwich for lunch.)

My mom also recalls another incident when she had to pick me up early from day care because the class was making peanut butter bird feeders. And I spent too many years of pre-adolescence eating lunch at the designated “peanut-free table.” Now, I can only dream of flying to visit my parents for Christmas without worrying about whether my seatmate’s snacks might induce anaphylaxis. And yes, kissing someone who has just eaten peanut butter would put my life in danger.

But are these pills and patches a true breakthrough for people like me?

I approached the question as I would any other assignment. I read the research, called immunologists, and spoke with economists and drug pricing experts about whether these treatments offer meaningful benefit.

One of the first things I heard: “We are still in the infancy of these treatments,” said Dr. Corinne Keet, a pediatric allergist at Johns Hopkins University.

Shefali Luthra (second from right), pictured in the seventh grade with her school math team, carried epinephrine in a fanny pack as a child, in case she had an allergic reaction. (The fanny pack, thankfully, has since been replaced with a purse.)(Courtesy of the Luthra family)

Medically, there’s a lot we don’t know about the risks, how much these drugs could help and how long any effects would last.

“None of these treatments have been shown to prevent fatal reaction,” Keet emphasized.

The idea behind them is to desensitize people. Aimmune’s “peanut pill” is modeled on the oral therapies some specialists use to wean allergic kids back on to nuts. This approach has gained popularity in recent years, especially for children with multiple allergies, or when it’s a substance particularly hard to avoid.

A colleague’s young daughter, who was born with multiple allergies, used that very treatment, as did a younger cousin of mine who, for the first several years of her life, was allergic to — not joking — almost everything but fruits and vegetables. In my case, this therapy came into vogue after I was too old to have a good chance of it weakening my sensitivities.

How it works: Kids ingest tiny, escalating doses of peanut protein. They then stay on peanut protein — Aimmune recommends the pill, though other doctors I spoke to suggested a little bit of peanut — as a maintenance drug.

But it’s unclear how much the new therapies would improve upon that ad hoc oral immunotherapy allergists are already offering. Instead of drugs, they use store-bought peanut protein, usually de-fatted peanut flour available online for as little as $1 a pound. This method isn’t approved by the Food and Drug Administration, and often isn’t covered by insurance — though doctors’ visits can be billed as “food challenges” or other visits that are typically covered.

In contrast, Aimmune’s product is expected to cost between $5,000 and $10,000 for the first six months of use, and $300 to $400 per month after. Analysts predict DBV’s will cost more than $6,000 for a year’s supply, though the company says it has not yet determined a price. DBV, Aimmune’s chief rival, has come up with a wearable skin patch that would transmit tiny, desensitizing protein doses. It declined to estimate a price, but it does not view oral immunotherapy as a competitor, said Joseph Becker, a company spokesman.

“There’s excitement, there’s caution and a lot of unanswered questions,” warned Dr. Erwin Gelfand, a pediatrics and immunology professor at the University of Colorado.

According to Aimmune’s results, published in the prestigious New England Journal of Medicine, two-thirds of allergic children could ingest 600 milligrams of peanut without harm after going through treatment.

To be clear, even with Aimmune’s help, someone like me still couldn’t safely eat PB&J. But it would desensitize me enough that I could taste a friend’s wine even if he recently ate pad thai.

Still, the treatment comes with caveats.

While 496 children started the trial, only 372 completed it. Of the 20 percent who backed out, half did so because of adverse events. About 14 percent of kids getting treatment still had to take epinephrine, and one experienced anaphylaxis, a severe reaction that can involve rashes, vomiting, a tightening throat and difficulty breathing. (For an allergic kid, even the possibility is maybe one of the most terrifying things you can imagine.)

Children who completed the regimen still had to take small doses of peanut protein daily, either the Aimmune drug or a controlled peanut serving. Statistically significant benefits were clear only in patients through age 17, though Dr. Daniel Adelman, the company’s chief medical officer, said Aimmune plans to do a follow-up trial for adults.

And the results don’t indicate who is likely to benefit, or how long improvements would last. That’s impossible to know, Adelman said, though he suggested accidental peanut exposure is scary enough — and pure avoidance ineffective enough — that the treatment is still worth it.

But all this means that anyone who has gone through Aimmune’s regimen would still want to carry epinephrine, and try to avoid peanuts.

“Not everybody responds well,” Gelfand said. When you factor in those details, the results are “not all that impressive,” he argued.

Dr. Tina Sindher, a pediatric allergist at Stanford University, pointed out that the Aimmune pill is a repackaged, clinically tested version of that homegrown oral therapy many allergists have already been using. DBV’s peanut patch, Viaskin, to a lesser extent, is the same — more convenient, perhaps, and more regulated, but still a variation on the existing medical approach.

“This concept has been around for a long time,” she said.

What’s new is the addition of labor, standardization and federal oversight — which companies then say demonstrates increased value.

It highlights a pattern I’ve noticed from my reporting: Drugmakers develop medication that refines a low-tech remedy, run a clinical trial to secure FDA approval, and then sell it at a higher price. For pharma, it’s a logical way to profit. But it puts patients in a bind.

“The hard outcome is we have these new products and they’re just about as good or slightly better than what we have,” said Nicholson Price, an assistant professor at the University of Michigan Law School, who studies drug pricing. “And they’re a lot more expensive.” He noted: “That’s when the choices get hard, and we’re not good at making hard choices.”

Also skeptical? The closest authority I know: my mother, who raised me with peanut allergies when they were more or less unheard of, and is now doing it all over again for my 10-year-old brother. (My other brother, my twin, was allergy-free until about a year ago.)

“It’s not worth it,” my mom told me. Her concern? Getting any of us to maintain a peanut dose — without knowing how long that reduced sensitivity would last — could induce what she called “a false sense of security.”

This thinking isn’t out of line, Sindher suggested. The way these studies are touted, she said, often “gloss over the fact that there’s a lot we don’t know.”

So for now, I’ll have to maintain my distance from the newsroom stash of Reese’s Pieces. My epinephrine and I aren’t parting ways anytime soon.


KHN’s coverage of children’s health care issues is supported in part by the Heising-Simons Foundation.

Pursuing the Dream of Healthy Aging

Photo

Credit Paul Rogers

Given their druthers, most people would opt for a long and healthy life. Few relish the idea of spending years, even decades, incapacitated by illness, dependent on caregivers and unable to enjoy the people, places and activities that make life worth living.

In 1980, Dr. James F. Fries, a Stanford University physician who studied chronic disease and aging, proposed that a “compression of morbidity” would enable most people to remain healthy until a certain age, perhaps 85, then die naturally or after only a brief illness.

Now, a prescient group of experts on aging envisions a route to realizing Dr. Fries’s proposal: one or more drugs that can slow the rate of aging and the development of the costly, debilitating chronic ailments that typically accompany it. If successful, not only would their approach make healthy longevity a reality for many more people, but it could also save money. They say that even a 20 percent cut in how fast people age could save more than $7 trillion over the next half-century in the United States alone.

“Aging is by far the best predictor of whether people will develop a chronic disease like atherosclerotic heart disease, stroke, cancer, dementia or osteoarthritis,” Dr. James L. Kirkland, director of the Kogod Center on Aging at the Mayo Clinic, said in an interview. “Aging way outstrips all other risk factors.”

He and fellow researchers, who call themselves “geroscientists,” are hardly hucksters hawking magic elixirs to extend life. Rather, they are university scientists joined together by the American Federation for Aging Research to promote a new approach to healthier aging, which may — or may not — be accompanied by a longer life. They plan to test one or more substances that have already been studied in animals, and which show initial promise in people, in hopes of finding one that will keep more of us healthier longer.

As Dr. Kirkland wrote in a new book, “Aging: The Longevity Dividend”: “By targeting fundamental aging processes, it may be possible to delay, prevent, alleviate or treat the major age-related chronic disorders as a group instead of one at a time.”

His colleague S. Jay Olshansky, a gerontology specialist in the School of Public Health at the University of Illinois in Chicago, said it is often counterproductive to treat one disease at a time. Preventing cardiac death, for example, can leave a person vulnerable to cancer or dementia, he explained.

A better approach, Dr. Kirkland said, would be to target the processes fundamental to aging that underlie all age-related chronic diseases: chronic low-grade inflammation unrelated to infection; cellular degradation; damage to major molecules like DNA, proteins and sugars; and failure of stem cells and other progenitor cells to function properly.

The team, which includes Dr. Nir Barzilai, director of the Institute for Aging Research at Albert Einstein College of Medicine in The Bronx, and Steven N. Austad, who heads the biology department at the University of Alabama at Birmingham, plans to study one promising compound, a generic drug called metformin already widely used in people with Type 2 diabetes. They will test the drug in a placebo-controlled trial involving 3,000 elderly people to see if it will delay the development or progression of a variety of age-related ailments, including heart disease, cancer and dementia. Their job now is to raise the $50 million or so needed to conduct the study for the five years they expect it will take to determine whether the concept has merit.

The project represents a radical departure from ordinary drug studies that test treatments for single diseases. However, the group, spearheaded by Dr. Barzilai, said the Food and Drug Administration has endorsed their idea to test a single substance for effectiveness against a range of ailments.

“If metformin turns out not to work, there are several other substances in the pipeline that could be tried,” Dr. Barzilai said. “Under the auspices of the National Institute on Aging, three research centers have tested 16 substances in different animal models and got incredible results with four of them.”

Green tea, one of those tested, bestowed no health or life span benefits, despite its popularity. But the drug rapamycin, an immune modulator used following organ transplants, was most effective among those tested, Dr. Barzilai said.

The team is starting with metformin because it is a cheap oral drug — costing about two cents a pill — with six decades of safe use in people throughout the world. Among those with Type 2 diabetes who have taken it for years, there is evidence suggesting that, in addition to diabetes, it protects against cardiovascular disease, cancer and possibly cognitive impairment, Dr. Kirkland said, adding that “it targets the fundamental processes of aging, which tend to be linked.”

Dr. Barzilai said, “Our goal is to establish the principle of using a drug, or two in combination, to extend health span. The best we can expect from metformin is two or three additional years of healthy aging. But the next generation of drugs will be much more potent.”

Dr. Barzilai is already conducting a complementary study of centenarians, the results of which could identify more drugs to delay age-related diseases. He and colleagues are isolating genes that appear to keep these long-lived men and women healthy for 20 to 30 years longer than other people and shorten the length of illness at life’s end. Several studies have already found that individuals with exceptional longevity experience a compression of morbidity and spend a smaller percentage of their life being ill, Dr. Barzilai and his colleague Dr. Sofiya Milman wrote in the “Aging” book.

By analyzing the action of genes that extend health span, “it should be possible to devise drugs that mimic the genes’ effects,” he said. Two such gene-based drugs that show early promise against age-related diseases are already being tested.

But until definitive studies are completed and substances are shown to be safe as well as effective in prolonging health, Dr. Olshansky cautioned against dosing oneself prematurely with widely touted substances like resveratrol, the antioxidant found in red grapes and wine, or growth hormone.

Consumers must exercise caution, he warned, because “there’s an entire industry out there trying to market the products we’re testing before they are adequately evaluated.”

He also emphasized that taking a drug found to ward off age-related ills is not a license to abandon a healthy lifestyle. Doing so “could completely negate the benefit of a compound that slows aging,” he said.

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