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An experimental drug being developed by Regeneron Pharmaceuticals Inc. (REGN) and Sanofi SA (SNY) showed promising results during a small, mid-stage clinical trial in treating a subset of patients with moderate to severe asthma, but some physicians cautioned that it was too early to say how effective the treatment may ultimately be.

The drug, dupilumab, is considered one of Regeneron’s most promising pipeline drugs and could eventually reach $750 million in annual U.S. sales if it gains U.S. approval to treat asthma, according to Barclays. Regeneron and Sanofi, which have a partnership to co-develop certain experimental drug programs, are also testing the drug to treat a type of eczema, the itchy skin condition, and have said dupilumab could eventually be applied to other allergic conditions.

Results from the trial, published online Tuesday in the New England Journal of Medicine, showed that dupilumab reduced asthma attacks by 87% in patients taking the drug compared to those receiving a placebo. Side effects of the drug appeared to be relatively consistent with those of patients taking placebos.

“It really raises the possibility that we’ve hit upon a fundamental pathway that’s driving the allergic reaction in asthma,” said George D. Yancopoulos, Regeneron’s chief scientific officer, in an interview.

However, the trial was relatively small, enrolling 52 patients in each of the study’s two treatment groups. An editorial accompanying the study results said the trial design, in which patients were gradually weaned off of standard therapies for asthma, did not reflect a “real world” environment.

It’s also unclear how large a swath of asthma patients will benefit from the drug, because only those with higher-than-normal disease-fighting white blood cells were admitted to the study, Michael E. Wechsler, director of the asthma program at National Jewish Health, a Denver-based research hospital that specializes in respiratory conditions, wrote in the editorial. Just 21% of patients screened for the trial met the inclusion criteria, Dr. Wechsler wrote.

Asthma affects more than 24 million people in the U.S., but existing therapies are unable to control the condition for as many as 10% to 20% of patients, according to the study’s authors.

The drug will advance into a larger phase-two trial, which will have four to five times as many patients as the trial published Tuesday, said Regeneron’s Mr. Yancopoulos.

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Dupilumab is a monoclonal antibody designed for the treatment of atopic diseases.^[1] It binds to the alpha subunit of the interleukin-4 receptor.^[2] Through blockade of IL-4R alpha, dupilumab modulates signaling of both the IL-4 and IL-13 pathway, which have been implicated in the pathophysiology of allergic disease.^[3]

This drug was developed by Regeneron Pharmaceuticals.

On May 21/2013 mid-stage data was presented at the American Thoracic Society meeting and published in the NEJM demonstrating a 87% reduction in asthma exacerbations in patients with moderate-to-severe allergic asthma.^[2]

1.  Statement On A Nonproprietary Name Adopted By The USAN Council – Dupilumab,American Medical Association.
2. ^ Jump up to:^a b Dupilumab in Persistent Asthma with Elevated Eosinophil Levels – Sally Wenzel, M.D., Linda Ford, M.D., David Pearlman, M.D., Sheldon Spector, M.D., Lawrence Sher, M.D., Franck Skobieranda, M.D., Lin Wang, Ph.D., Stephane Kirkesseli, M.D., Ross Rocklin, M.D., Brian Bock, D.O., Jennifer Hamilton, Ph.D., Jeffrey E. Ming, M.D., Ph.D., Allen Radin, M.D., Neil Stahl, Ph.D., George D. Yancopoulos, M.D., Ph.D., Neil Graham, M.D., and Gianluca Pirozzi, M.D., Ph.D., NEJM.
3.  Regeneron press release March 2, 2013

Researchers have developed a new drug to treat the underlying pathology associated with asthma, reducing flare-ups by nearly 87%, according to results of a new trial. Some experts view this as a potential game changer if the drug lives up to its early performance in a smallstudy of 104 patients, recently presented at theAmerican Thoracic Society InternationalConference in Philadelphia.

Dupilumab, an injectable medication developed by Regeneron Pharmaceuticals REGN -3.76% Inc. and Sanofi , has sparked the interest of many pulmonologists and as well as critical care physicians, and represents a new class of drug to treat this disabling, as well as costly disease. It is estimated that approximately 25 million people in the United States are known to have asthma. The worldwide estimates are between 235-300 million people, with 180,000 deaths annually.

Asthma is a chronic inflammatory disease of the airways associated with airway sensitivity with multiple triggers leading to acute and chronic narrowing of the airway with increased mucus production. Patients with asthma exacerbations experience wheezing, chest tightness, shortness of breath, and coughing. In severe cases, these symptoms can be life-threatening. For the majority of asthma patients, standard treatments can control the disease.

However, an estimated 10% to 20% of asthmatic patients are less than optimally controlled despite existing therapies. Moderate-to-severe asthma is generally recognized as a so called heterogeneous disease; the Th2 (Type 2 helper T cell) inflammation pathway is believed to play a role in disease pathogenesis in approximately 50% of these patients.

Based on results of this small study, Dupilumab helped to improve symptoms and standard measures of lung function and reduced the need for standard drugs such as long acting beta agonists (LABA) and anti-inflammatory medications such as steroids.

Dupilumab works by simultaneously blocking proteins that have been linked to inflammation, interleukin-4 (IL-4) and interleukin-13 (IL-13). In the past, other pharmaceutical companies have investigated medications that block one or both of the proteins, but without success.

On May 21, Sanofi and Regeneron Pharmaceuticals, Inc. jointly announced publication online in the New England Journal of Medicine of positive results from a Phase 2a study of dupilumab in patients with moderate-to-severe allergic-type asthma. The study results were presented at the American Thoracic Society 2013 International Conference.

Dupilumab is a monoclonal antibody targeting the alpha subunit of the interleukin 4 receptor (IL-4R alpha), which regulates signaling of both IL-4 and IL-13, drivers of Th2 (Type 2 helper T cell) immune response.

The proof-of-concept study enrolled 104 patients with moderate-to-severe, chronic asthma that was not well controlled with inhaled glucocorticosteroids (ICS) and long-acting beta agonist (LABA) therapy, and who had elevated blood or sputum eosinophils (immune cells used as a marker of Th2 asthma in this study).

The primary objective of the trial was to assess the effect of subcutaneous dupilumab, administered weekly at a dose of 300 milligrams (mg) for twelve weeks. Patients were treated with dupilumab (N=52) or placebo (N=52) in addition to ICS and LABA therapy for the first four weeks of the study. The LABA was withdrawn at week four and the ICS was tapered to withdrawal between the sixth and ninth week.

Patients were treated for 12 weeks or until they experienced a protocol-defined asthma exacerbation, the primary endpoint of the study. 23 patients (44.2%) receiving placebo experienced an asthma exacerbation compared to three patients (5.8%) receiving dupilumab, resulting in an 87% reduction in the incidence of asthma exacerbations for the dupilumab arm compared to placebo (p<.001).

Statistically and clinically significant improvements were observed for measures of lung function and other asthma control parameters, such as forced expiratory volume over one second (FEV1) (difference from baseline to week 12 between dupilumab and placebo of 0.27 L)

Adverse events (AEs) were reported by a similar proportion of patients in both groups (76.9% placebo; 80.8% dupilumab). AEs were generally non-specific and of mild-to-moderate intensity. The most common AEs for dupilumab were injection-site reaction (28.8%), nasopharyngitis (13.5%), upper respiratory tract infection (13.5%), headache (11.5%) and nausea (7.7%).

A fair number of patients with moderate-to-severe, persistent allergic type asthma are not well controlled despite standard therapy placing them at risk for repeated exacerbations hospitalizations and negative outcomes.

It is estimated that standard drugs are typically unable to control asthma well in about 10% to 20% of patients. The inflammation caused by Th2 cells, the type of inflammation among patients they tested, is a factor in nearly half of these moderate to severe cases, representing nearly 2.5 million people in the US and up to 30 million throughout the world.

Dupilumab, through blockade of IL-4R alpha, modulates signaling of both the IL-4 and IL-13 pathways, which have been implicated in the pathophysiology of Th2 mediated diseases such as asthma and atopic dermatitis.

Along with previously reported positive proof-of-concept clinical results of dupilumab in atopic dermatitis presented at the recent Amercian Academy of Dermatology (AAD), data from the present study supports the concept that blocking the IL-4/IL-13 pathway is encouraging as an method to treat multiple allergic conditions. Phase 2b trials with dupulimab in both asthma and atopic dermatitis will be forthcoming.

Data from asthma patients as well as those with atopic dermatitis suggests that this new antibody may affect a common pathway shared by these two allergic diseases.

If Dupilumab is approved, it may be a significant advance for patients with moderate to severe persistent asthma that is not well controlled by standard drugs.

Dupilumab is a drug that can treat the root cause of asthma.Strategies to treat asthma have, for the most part, dealt with only the symptoms, without addressing the underlying mechanism or ultimate cause.