Fitting in

The approval of dupilumab (Dupixent, Sanofi Regeneron) for moderate-to-severe atopic dermatitis adds a much-needed option that may alter the broader course of atopic disease, experts told Dermatology Times. As with any biologic drug, they add, dermatologists likely will need to advocate for insurance coverage.

Blazing new trails

Dr. Blauvelt“The FDA approval of dupilumab fulfills an unmet need for dermatologists who care for patients with more severe eczema. These patients have been suffering, with very few good options available for many years. This is going to be a trailblazer for practitioners who are trying to manage these difficult patients,” said Andrew Blauvelt, M.D., M.B.A., president of the Oregon Medical Research Center. He was principal investigator on the phase 3 Randomized, Double-Blind, Placebo-Controlled Study to Demonstrate the Efficacy and Long-Term Safety of Dupilumab in Adult Patients with Moderate-to-Severe Atopic Dermatitis (CHRONOS; for more information on these data, please see story, page 42).

“For patients,” said Emma Guttman-Yassky, M.D., Ph.D., “it’s amazing. We now have moderate-to-severe patients who were treated by community dermatologists, allergists or other physicians for many years - with only topical or oral steroids, phototherapy or other systemics such as the immune suppressant cyclosporine - and nothing worked. ... They

Dr. Guttman-Yasskyfinally have a treatment that is safe” for long-term use. She is professor and vice chair, department of dermatology, Icahn School of Medicine at Mount Sinai.

Lawrence F. Eichenfield, M.D., adds, “Dupilumab is the first biologic agent developed, and approved, for atopic
dermatitis. Our more severe atopic dermatitis patients are miserably impacted by their disease, and the promise of successful biologic therapy is a life-changer. There is real excitement - among dermatologists, patients and their families.”

He is chief of pediatric and adolescent dermatology, professor of dermatology and pediatrics and vice chair, department of dermatology, at the University of California, San Diego School of Medicine.

Treating moderate-to-severe AD has long been challenging, Dr. Blauvelt says, because therapy for more severe disease has involved broadly acting immunosuppressants that bring numerous difficulties and side effects with long-term use.

Eric L. Simpson, M.D., M.C.R., explains, “Because of a lack of good options, dermatologists often prescribe systemic steroids for adults with moderate to severe atopic dermatitis,” a practice that all treatment guidelines discourage.

“Dupilumab provides a novel option that is targeted, thus minimizing side effects that are encountered with less specific systemic therapies such as systemic steroids and other traditional immunosuppressants.”

Mechanism of action

Dr. PallerDupilumab blocks the interleukin 4 (IL-4) receptor alpha subunit (IL-4Rα), which blocks signaling of both IL-4 and IL-13, 2 cytokines required for the T helper cell 2 (Th2) response. Dr. Simpson is professor and director of clinical trials in the Oregon Health Sciences University department of dermatology.

Thanks to dupilumab, Amy Paller, M.D., says, “Many of our patients will be able to transition off of immunosuppressants that they’ve been on for a long time. Despite long-term use of systemic medications, the AD for many patients is only partially controlled, and frequent laboratory testing is required to test for toxicity. It’s going to be a godsend for many people.”

She is chair, department of dermatology; director, Northwestern University Skin Disease Research Center (SDRC); and professor in of pediatrics at Northwestern University.

Next: Halting atopic march

Halting atopic march

As early biologic treatment for psoriasis appears to reduce or eliminate the development of some associated comorbidities, says Dr. Blauvelt, some experts speculate that timely administration of dupilumab might alter the broader course of atopic disease. “Most eczema appears first in childhood,” a precursor to the atopic march, leading to asthma over time, he says. “One of the thoughts with this drug is that if we can treat patients earlier, can we block development of asthma later down the road, and change the course of atopic dermatitis, making it less likely to persist into adulthood? Pediatric studies are just now getting underway, and their results are greatly anticipated.” 

Dr. EichenfieldDr. Eichenfield adds, “Our institution had some adults in the trials, including some former pediatric patients who brought their severe AD into adulthood, and they have done incredibly during the trial.” 

To date, he says, pediatric dupilumab studies have occurred outside the United States, “And we are eagerly awaiting our first children being in (U.S.) studies.  But already we are wondering if we can get off-label use of dupilumab for our most severely affected patients.”

Dr. Paller says, “Our studies, even in very early AD in babies, have shown the strong evidence of  Th2 activation in both the skin and in blood, suggesting the potential value of dupilumab for severely affected young children who are resistant to topical steroids, with the extra potential of changing disease course. I definitely will use it once safety has been proven in children, but in children safety is of the utmost importance.”

Ongoing studies, some of which Dr. Guttman-Yassky’s practice is participating in, are exploring dupilumab in children.

“We have many children right now who unfortunately need to be treated with cyclosporine. If dupilumab were proven safe and effective in children, I would gladly use it instead in this population. Children are different than adults” when it comes to AD, and it is paramount to establish safety before proceeding in this population.

Dr. Simpson adds, “I have treated more than 35 patients with the drug in the trials for more than two years now, and I have been extremely pleased with the results. More importantly, dupilumab has changed the lives of my patients, who can now function free of severe itch and eczema.”

Questions surround coverage

How will insurers handle dupilumab? “No one knows for sure,” Dr. Blauvelt says. “But all indications suggest that insurance companies will require dupilumab to be prescribed by a specialist such as a dermatologist or allergist.”

Dr. Paller says, “We hope that access won’t be a problem, and that our patients will not have to fail something like cyclosporine before they can start dupilumab.”

Dr. Guttman-Yassky says that many of her patients have qualified for insurance coverage of dupilumab because they failed so many previous treatments. “Just in my clinic, I have 40 patients (besides approximately 30 clinical-trial patients who have now transitioned to various insurances) who qualified for insurance on this drug. That’s a large number” considering how new it is.

Regarding pricing, says Dr. Eichenfield, “I am pleased that Regeneron and Sanofi have worked proactively with insurers to establish pricing levels that are significantly lower than those of multiple biologic agents for psoriasis.” Dupilumab’s U.S. wholesale acquisition cost is $37,000 annually.¹

Nevertheless, he expects that dermatologists will need to advocate for their patients to get the drug.

“Dermatologists will be responsible for ensuring that patients with refractory AD, poor control despite consistently used topical therapies and patients who failed prior systemic therapies are the ones pursuing coverage,” Dr. Eichenfield says.

Dr. Simpson says that when one considers the impact of AD on patients’ lives and productivity, plus the reduction in complications and overall disease burden dupilumab delivers, including its potential effects on comorbidities, “The cost-benefit analysis from my clinician and advocate’s perspective appears very favorable.” He advises dermatologists to join the National Eczema Association and use its resources to help advocate for their patients to get the right drug for their diagnosis. ƒ

Disclosures: Dr. Blauvelt has been a scientific advisor, clinical investigator and/or speaker for Abbvie, Amgen, Boehringer Ingelheim, Celgene, Dermira, Genentech, GlaxoSmithKline, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Sandoz, Sanofi-Genzyme, Sun Pharma, UCB and Valeant. Dr. Guttman-Yassky is a consultant for Sanofi/Regeneron, and her laboratory did biopsy analyses for dupilumab’s Phase 1 and 2 studies. She also consults with all major companies providing or developing products for atopic dermatitis. Drs. Eichenfield and Paller have served as consultants to Sanofi/Regeneron.

References

1. Regeneron, Sanofi. Regeneron and Sanofi announce FDA approval of Dupixent (dupilumab), the first targeted biologic therapy for adults with moderate-to-severe atopic dermatitis. http://investor.regeneron.com/releasedetail.cfm?releaseid=1019097. Published March 28, 2017. Accessed April 4, 2017.