AAAAI News: Dupilumab Remission; Tezepelumab in Severe Asthma; Palforzia Safety

Dupilumab Led to Asthma Remission for Some

About 30 percent of patients taking the biologic drug dupilumab experienced “remission” of asthma symptoms after six months of treatment, while 20 percent were able to remain largely asthma symptom-free for one year, a 2021 study finds.

Researchers defined remission as the near absence of asthma symptoms, based on several measures of asthma control including exacerbations, scores on an asthma symptom self-assessment and a lung function test.

“These patients met none of the three criteria for remission when they started, and at six months, one-third had achieved all three of the remission criteria,” Dr. Ian Pavord, lead study author and a professor of respiratory medicine at University of Oxford in England told Allergic Living. “Even those who didn’t meet the remission criteria were clearly better than those who didn’t achieve it.”

The study, presented at the 2021 American Academy of Allergy, Asthma and Immunology (AAAAI) Virtual Annual Meeting, included data on 348 patients with uncontrolled, moderate to severe asthma given either a 200- or 300-milligram injection of dupilumab every two weeks, and 195 patients given a placebo.

Researchers focused on three key measures of asthma control: exacerbations, scores on an asthma symptom questionnaire, and forced expiratory volume (FEV1), a test that measures how much air can be breathed out in one second.

Levels of Symptom Control

After six months on the drug (brand name: Dupixent), 83 percent of those in the treatment arm were exacerbation free, compared to 61 percent on placebo.

Likewise, after six months of treatment, 57.5 percent of patients had scores on an asthma symptom questionnaire indicating they were having few asthma symptoms, compared to 27 percent on placebo. The questionnaire included factors such as how often wheezing or shortness of breath led to waking up at night or limiting activities.

Finally, at the six-month mark, 30 percent of patients met the first two remission criteria, and also scored in the normal range on the lung function test, measured after they took a rescue inhaler. Fewer than 5 percent in the placebo group achieved this.

After one year, the number of patients who continued to meet all three remission criteria fell to 20 percent. This is not surprising, Pavord says. Other health conditions or illnesses such as viruses can cause asthma symptoms to flare from time to time, even in those will well-controlled asthma. “It’s harder to achieve remission for 12 months than six months. Things will happen that will knock you off your perch,” he says.

Tezepelumab vs. Severe Asthma

In a large Phase 3 clinical trial, the biologic drug tezepelumab was able to reduce asthma exacerbations by 56 percent over a year in adult and teen patients with severe, uncontrolled disease. The rate of reduction is considered clinically meaningful.

Tezepelumab is a monoclonal antibody designed to work at an early stage of immune system response in the airways, blocking TSLP (thymic stromal lymphopoietin). TSLP is a type of cytokine, or signaling molecule, that triggers immune system defenses. In response to a trigger, TSLP cytokines set off a cascade of airway inflammation that leads to asthma symptoms.

The results of the Navigator Phase 3 study were presented at the 2021 AAAAI virtual meeting. In Navigator, more than 1,000 teen and adult patients with poorly controlled asthma and frequent exacerbations were divided into two groups. They received either tezepelumab or placebo (but did not know which, as the trial was “blinded”). The participants also remained on their standard asthma regimens of inhaled corticosteroid inhalers, plus at least one additional controller medication.

“These are ground-breaking results for the many patients with severe asthma who continue to face debilitating symptoms despite receiving standard of care inhaled medicines and currently approved biologics,” said lead author Dr. Andrew Menzies-Gow, director of the lung division at London’s Royal Brompton Hospital. In addition to reducing exacerbations in most trial participants, the injectable biologic also improved lung function and quality of life scores.

TSLP cytokines initiate an overreactive immune response in allergic, eosinophilic and non-allergic forms of asthma. In blocking that response in several types of asthma, tezepelumab may open the door to a treatment option for those who don’t respond to other biologics.

“Tezepelumab has the potential to transform treatment for a broad population of patients with severe asthma regardless of their type of inflammation, including those with and without an eosinophilic phenotype,” said Menzies-Gow.

However, one drawback with tezepelumab is that, in previous a trial, it did not attain a goal to allow for the reduction of corticosteroid use. In this study, adverse effects were limited to upper respiratory infections and headaches, in both the active drug and placebo groups.

Pharmaceutical collaborators Amgen and AstraZeneca plan to apply for regulatory approval for tezepelumab.

Palforzia OIT Safety at 3.5 Years

An analysis of 3.5 years of safety data on patients taking Palforzia, the FDA-approved oral immunotherapy for peanut allergy, shows a marked drop in treatment-related symptoms once the daily maintenance dose is reached.

At the 2021 AAAAI virtual meeting, lead author Dr. Thomas Casale of the University of South Florida presented data pooled from three controlled studies in North America and Europe, as well as from three extension studies. The findings, which involved 1,127 trial participants, show that adverse effects occurred largely during the six months of gradual updosing with Palforzia.

Most reactions during the six months were mild (57.9 percent) or moderate (26.2 percent), and then decreased sharply once patients reached maintenance. By Year 3 on treatment, mild and moderate adverse effects fell to 5.8 percent and 1.4 percent, respectively. The most frequently reported treatment-related symptoms were throat irritation or itchiness, and abdominal pain.

During the 3.5 years of OIT, 1.2 percent of participants experienced a serious systemic allergic reaction related to the therapy (such reactions also decreased in frequency over time). Those affected were treated successfully with epinephrine.

Palforzia is approved as a desensitizing therapy, to protect against accidental peanut exposures in allergic patients aged 4 to 17. The daily maintenance dose of Palforzia is 300 milligrams (about one peanut kernel) in powder form, which is mixed into food. That level is an important safety indicator Casale says, since “if you are able to tolerate 300 mg of peanut, you can prevent about 95 percent of reactions.”