Asthma is a chronic lung condition characterized by recurrent attacks of breathlessness and wheezing that affect over 300 million people worldwide. For many asthma patients, allergies are a major trigger for these asthma attacks. Allergic asthma occurs when the immune system overreacts to otherwise harmless allergens like pollen, dust mites, or pet dander. When these allergens are breathed in, they can cause the airways to become swollen and inflamed, leading to the symptoms of an asthma attack.
While there is currently no cure for asthma, significant advances have been made in developing targeted therapeutics to better treat and manage allergic asthma. Let's take a look at some of the most promising new treatment options.
Monoclonal Antibody Therapies
Monoclonal antibodies are laboratory-produced molecules that can precisely target specific components of the immune system involved in allergic inflammation. One such antibody therapy is omalizumab (Xolair), which targets immunoglobulin E (IgE), the antibody that plays a central role in allergic responses. By binding to free IgE molecules, omalizumab prevents them from activating immune cells to launch an allergic attack. Clinical studies have shown omalizumab can significantly reduce asthma exacerbations in patients with moderate-to-severe allergic asthma when added to standard inhaled corticosteroids.
Other monoclonal antibodies in development target different components of the allergic response such as IL-4, IL-5, and IL-13 - cytokines that drive the production of inflammatory cells that cause asthma symptoms. Dupilumab, which targets the IL-4/IL-13 pathway, was recently approved for use in patients with moderate-to-severe asthma who have Type 2 inflammation fueled by these cytokines. In clinical trials, dupilumab provided greater asthma control and reduced exacerbations compared to placebo when combined with standard therapies.
Oral Treatments
While inhalers remain a first-line treatment, oral medications may provide an effective option for some patients struggling to control their asthma through inhalation alone. One such oral treatment is daxas (roflumilast). This drug works by inhibiting the PDE4 enzyme to reduce inflammatory cell activity in the lungs and lessen asthma symptoms. A large clinical trial found that adding oral daxas to standard long-acting bronchodilator therapy provided an additional reduction in exacerbations in patients with severe asthma and a history of exacerbations despite inhaled corticosteroid use.
Another oral treatment currently in late-stage clinical trials is Fevipiprant, an antagonist of the prostaglandin D2 receptor CRTH2 that reduces levels of inflammatory prostaglandins in the airways. Early phase 2 studies of Fevipiprant have demonstrated reduced exacerbation rates versus placebo in patients with moderate-to-severe asthma and confirmed Type 2 disease. If approved, it could give patients an important oral adjunct treatment option.
Biologic Therapies
For severe Allergic Asthma Therapeutics patients who remain uncontrolled despite maximally-tolerated standard therapies, biologics targeting specific pathogenic pathways may offer promise. Two such biologic therapies are benralizumab and reslizumab. Benralizumab is an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody that depletes eosinophils, a type of white blood cell linked to exacerbations. In late-stage clinical trials, monthly subcutaneous benralizumab significantly reduced exacerbations in patients dependent on oral corticosteroids or with a history of prior exacerbations.
Reslizumab is an interleukin-5 antagonist that inhibits the production and function of eosinophils. Intravenous reslizumab treatment every 4 weeks resulted in clinically meaningful improvements in lung function and reduced exacerbation rates in Phase 3 clinical trials. Both benralizumab and reslizumab have since gained FDA approval for use in patients with severe eosinophilic asthma. For those inadequately controlled on standard-of-care treatments, these biologics offer welcome new options to help lower exacerbation risk.
The Future of Precision Therapies
Going forward, it is hoped that advances in precision diagnostics can help match particular molecular phenotypes with targeted therapeutics. For example, patients with characteristics of Type 2-high inflammation may benefit most from therapies blocking Th2 cytokines like IL-4/IL-13 or eosinophils. Meanwhile, those with noneosinophilic asthma dominated by neutrophilic inflammation may respond better to novel anti-neutrophilic treatments. Gene sequencing may also uncover specific genetic variants predictive of treatment response.
Combination therapies blocking multiple aspects of the allergic pathway simultaneously may prove even more effective than monotherapies in achieving full control of severe asthma. Immunomodulatory drugs influencing both the innate and adaptive arms of the immune response also represent promising areas for future exploration. Ultimately, continued refinement of molecular phenotyping and precision-guided therapy holds great promise to maximize asthma control for all patients, regardless of their specific pathogenic mechanism.
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