[Updated: 11:05 pm ET] Regeneron Pharmaceuticals became a breakout biotech star with a new drug for treating age-related macular degeneration, the leading cause of blindness among the elderly in the U.S. Now the Tarrytown, NY-based biotech believes it’s taken a big step towards creating a potential asthma drug.
Regeneron unveiled the full results of a mid-stage study today testing its drug, dupilumab, in patients with moderate-to-severe allergic asthma (the company released an abstract version of the results in March ahead of the American Thoracic Society’s International Conference). The data are not only promising, but have Regeneron talking blockbuster, meaning it could someday generate more than $1 billion in annual sales. Results were published online in the New England Journal of Medicine. [Updated to include link to journal article.]
Asthma affects about 25 million people in the U.S. and as much as 300 million overall worldwide. Regeneron is currently targeting a subset of about 10 percent to 20 percent of those patients—those whose asthma can’t easily be controlled by existing inhalable treatments that help open up the airways, such as inhaled glucocorticosteroids like AstraZeneca’s budesonide (Pulmicort), or long-acting beta-agonists, or LABAs (GlaxoSmithKline’s fluticasno/salmeterol (Advair).
Dupilumab is a monoclonal antibody taken by an injection just under the skin that patients can give themselves at home or work. Regeneron is anticipating a dosing schedule that would involve injections every “couple of weeks” or once a month, according to chief scientific officer George Yancopoulos.
The drug is designed to work by blocking the interleukin 4 and interleukin 13 receptors, which scientists believe are involved in allergic asthma attacks. Regeneron believes this mechanism is at the core of allergic asthma, and potentially other allergic diseases, opening the door for big returns for the company if it can prove the idea turns into a real benefit for patients. Regeneron is already testing the drug in patients with atopic dermatitis, or eczema, but it is also considering expanding the drug’s scope into other allergies, according to Yancopoulos.
“We’re using a biologic that’s targeted right at the molecular trigger of this whole disease pathway,” says Yancopoulos. “It could be a true blockbuster. It could really provide a game-changing therapy for a lot of the patients with a lot of need out there.”
That all starts with the clinical trials in asthma. For the mid-stage study, Regeneron picked patients representing roughly half of the “serious” asthma population, according to Yancopoulos. The company selected patients with a high count of eosinophils—a type of white blood cell commonly seen in patients with an allergy-induced form of asthma, as opposed to those with a form of disease that appears after intense exercise. .
“We were using an antibody targeted to what we thought were the molecular triggers of this immune deviation,” he says. “[But] based on how impressively the drug worked it’s not clear whether the drug would need to be limited to this population.”
The study consisted of 104 patients overall, split into two equal-sized groups. One group was randomly assigned to get weekly 300-milligram injections of the Regeneron antibody, and the other half got a placebo. All patients were also treated with a glucocorticosteroid and a LABA therapy for four weeks before those therapies were tapered off: LABA was withdrawn after four weeks altogether, while the glucocorticosteroid was eliminated after between six and nine weeks of treatment. Patients stayed on the study for 12 weeks, or until researchers observed an “asthma exacerbation,” when their condition worsened in a way that would include, for example, a need to visit an emergency room.
“This study was intended to reflect what you might see in a much larger population followed over time when you haven’t backed off on these populations,” says Yancopoulos.
Regeneron’s goal in the study was to reduce those events, and it knocked that metric out of the park: 23 of the 52 patients (44 percent) taking the placebo had their condition worsen, compared to three (5 percent) of those taking dupilumab. That’s an 87 percent reduction in such events. Since exacerbations frequently lead to expensive trips to the hospital, this is the kind of data Regeneron will surely want to show to insurers someday, when it asks them to pay what will likely be a high price for its antibody drug.
Regeneron said the drug was well tolerated by patients—there was little difference in the mild side effects between both groups. It also noted that patients taking its drug achieved statistically significant improvements in their lung function and that those improvements weren’t the result of chance. Patients were allowed to use inhalers when their chests were feeling tight One measure of lung function Regeneron used in the study was the amount of inhales, or “puffs,” each patient took on those inhalers per day over the course of the 12 weeks. All patients coming in to the study were already averaging just over two puffs per day. The placebo patients increased to about 2.5 puffs per day during the study, while the treated patients decreased to less than one per day. The same trends were noted among typical asthma symptoms, Yancopoulos says.
Regeneron is planning a larger, 500-patient mid-stage study of dupilumab and hopes to start it in June. It is also planning a similar study testing the drug in atopic dermatitis in the near future as well. The drug is one of several that are part of Regeneron’s big partnership deal with Sanofi, which also includes afilbercept (Eylea) and a cholesterol-lowering drug in late-stage clinical trials that blocks the molecular target PCSK9. Regeneron will release data from that study next year.