Adele Graham-King, Contributing Editor09.08.16
Asthma is one of the world’s most common chronic conditions affecting health across a generalized population. It was thought to impact over 24 million people in the U.S. in 2014 (CDC, 2014). It is also the leading reason for school absence in children in the U.S., and suggested to have a financial burden on the U.S. healthcare system in the region of $56 billion in 2105.
Asthma is characterized by coughing, wheezing, a shortness of breath (dyspnea), tightness across the chest and difficulty breathing. In specific individuals it’s not always possible to know what the trigger is but it’s well documented that allergens such as dust, house mites, animal fur, smoking and exercise can stimulate an attack. It’s not even uncommon for a blast of cold air or a quick sprint to cause a problem.
It currently isn’t possible to cure asthma. The most effective treatment is prevention but we have yet to find a ‘quick fix’ during exacerbations of the condition or in an acute asthma attack.
Current medications for asthma are effective and facilitate a multi-pronged approach, and include inhaled corticosteroids, long-acting bronchodilators (beta-agonists and anticholinergics), theophylline, leukotriene modifiers, and more recent strategies such as the use of anti-immunoglobulin E (IgE) antibodies (omalizumab) and anti-IL-5 antibodies. For acute episodes of short-acting bronchodilators, systemic corticosteroids, and ipratropium are used to induce rapid bronchodilation and reduce spasm.
Aside from the fact that there are various different combinations of pharmacological agents for the management of long-term chronic symptoms of asthma, the gold standard remains within inhaled corticosteroids for both adults and children. Indeed the 2015 Global Initiative for Asthma outlined inhaled corticosteroids as the preferential treatment, a statement supported by a Cochrane review in 2012, which considered the effectiveness of corticosteroids with anti-leukotrienes and concluded that indeed inhaled steroids were superior in both adults and children with moderate asthma.
From an evolution of treatment viewpoint there are various issues associated with inhaled corticosteroids, of which there are several. Fluticasone, budesonide, mometasone, and beclamethasone are all used widely as a first choice of therapy in long-term prevention. However, they all need to be effectively inhaled in order to work. Although this isn’t necessarily an issue for older children and adults who use an actuated inhaler, this can be an almost impossible task for young children and babies. Even the elderly can struggle with the assembly and co-ordination required to activate drug delivery and devices.
Although the leukotriene inhibitors may be taken in pill form, they are generally more expensive and not licensed for use in very young children under the age of 2. The problem is that asthma simply isn’t selective and it can be severe in babies, children and adults all the same. The CDC estimated that 3,630 people died in the U.S. in 2013; however most of these deaths could have been avoided through adequate treatment and care. So the search goes on for even more effective, easy and safe to take treatments that could alleviate the burden that asthma puts on our health on a daily basis.
New drugs for any disease condition are hard to come by however in the search for asthma treatments a new class of drug is being investigated and recent research suggests that this holds promise. Fevipiprant, also known as QAW039, is an orally available prostaglandin D2 receptor 2 agonist currently being developed by Novartis for its effectiveness in preventing asthma symptoms. Fevipiprants action is against eosinophilic induced airway inflammation. Although the role of eosinophils in allergic airway inflammation isn’t completely understood, these little critters are recruited to the lungs during the immune response and result in antigen presentation and cytokine production. Cytokines are well documented for having a role in airway inflammation typically associated with asthma and sputum eosinophil percentage is an accurate marker for this. Values of this measure are typically raised from <1% in normals to >5% in patients with moderate to severe asthma.
Working on the basis that fevipiprant works to reduce the presence of eosinophils in the lungs, and therefore reduces eosinophil percentage, a research project was undertaken at the University of Leicester in the UK to investigate the effect of the drug as an add-on therapy in combination with other asthma therapies vs. placebo.
Although not a huge study, 61 patients were blindly split into two groups and given either fevipiprant or placebo on top of all their other medications for a period of 3 months. The primary end-point of the study was the reduction in eosinophil percentage from baseline to the end of the study. The promising results indicated a reduction in this measure from 5.4% to 1.1% in patients taking the active drug compared to 4.6% to 3.9% in the placebo group. This was regardless of other pharmacological asthma medications.
Furthermore patients that took the active drug recorded a reduction in all asthma symptoms, improved ability to complete daily activities and improved overall wellbeing, which deteriorated when the drug was stopped.
As we all know quality of life while taking medication is almost equally as important as clinical response, otherwise people simply don’t take it. If the reduction in clinical symptoms is truly as good as the effects on the biological markers indicate, then Novartis could have a winner. Cautious optimism is definitely the right attitude, but with larger longitudinal studies potentially on the horizon, and given the right formulation, the new little pill may be the road to taking the wheeze out of asthma.
Adele Graham-King
Contributing Editor
Adele is a design consultant who works in product development for medical and healthcare applications. Her background is in pharma, and she has a degree in applied physiology.
Asthma is characterized by coughing, wheezing, a shortness of breath (dyspnea), tightness across the chest and difficulty breathing. In specific individuals it’s not always possible to know what the trigger is but it’s well documented that allergens such as dust, house mites, animal fur, smoking and exercise can stimulate an attack. It’s not even uncommon for a blast of cold air or a quick sprint to cause a problem.
It currently isn’t possible to cure asthma. The most effective treatment is prevention but we have yet to find a ‘quick fix’ during exacerbations of the condition or in an acute asthma attack.
Current medications for asthma are effective and facilitate a multi-pronged approach, and include inhaled corticosteroids, long-acting bronchodilators (beta-agonists and anticholinergics), theophylline, leukotriene modifiers, and more recent strategies such as the use of anti-immunoglobulin E (IgE) antibodies (omalizumab) and anti-IL-5 antibodies. For acute episodes of short-acting bronchodilators, systemic corticosteroids, and ipratropium are used to induce rapid bronchodilation and reduce spasm.
Aside from the fact that there are various different combinations of pharmacological agents for the management of long-term chronic symptoms of asthma, the gold standard remains within inhaled corticosteroids for both adults and children. Indeed the 2015 Global Initiative for Asthma outlined inhaled corticosteroids as the preferential treatment, a statement supported by a Cochrane review in 2012, which considered the effectiveness of corticosteroids with anti-leukotrienes and concluded that indeed inhaled steroids were superior in both adults and children with moderate asthma.
From an evolution of treatment viewpoint there are various issues associated with inhaled corticosteroids, of which there are several. Fluticasone, budesonide, mometasone, and beclamethasone are all used widely as a first choice of therapy in long-term prevention. However, they all need to be effectively inhaled in order to work. Although this isn’t necessarily an issue for older children and adults who use an actuated inhaler, this can be an almost impossible task for young children and babies. Even the elderly can struggle with the assembly and co-ordination required to activate drug delivery and devices.
Although the leukotriene inhibitors may be taken in pill form, they are generally more expensive and not licensed for use in very young children under the age of 2. The problem is that asthma simply isn’t selective and it can be severe in babies, children and adults all the same. The CDC estimated that 3,630 people died in the U.S. in 2013; however most of these deaths could have been avoided through adequate treatment and care. So the search goes on for even more effective, easy and safe to take treatments that could alleviate the burden that asthma puts on our health on a daily basis.
New drugs for any disease condition are hard to come by however in the search for asthma treatments a new class of drug is being investigated and recent research suggests that this holds promise. Fevipiprant, also known as QAW039, is an orally available prostaglandin D2 receptor 2 agonist currently being developed by Novartis for its effectiveness in preventing asthma symptoms. Fevipiprants action is against eosinophilic induced airway inflammation. Although the role of eosinophils in allergic airway inflammation isn’t completely understood, these little critters are recruited to the lungs during the immune response and result in antigen presentation and cytokine production. Cytokines are well documented for having a role in airway inflammation typically associated with asthma and sputum eosinophil percentage is an accurate marker for this. Values of this measure are typically raised from <1% in normals to >5% in patients with moderate to severe asthma.
Working on the basis that fevipiprant works to reduce the presence of eosinophils in the lungs, and therefore reduces eosinophil percentage, a research project was undertaken at the University of Leicester in the UK to investigate the effect of the drug as an add-on therapy in combination with other asthma therapies vs. placebo.
Although not a huge study, 61 patients were blindly split into two groups and given either fevipiprant or placebo on top of all their other medications for a period of 3 months. The primary end-point of the study was the reduction in eosinophil percentage from baseline to the end of the study. The promising results indicated a reduction in this measure from 5.4% to 1.1% in patients taking the active drug compared to 4.6% to 3.9% in the placebo group. This was regardless of other pharmacological asthma medications.
Furthermore patients that took the active drug recorded a reduction in all asthma symptoms, improved ability to complete daily activities and improved overall wellbeing, which deteriorated when the drug was stopped.
As we all know quality of life while taking medication is almost equally as important as clinical response, otherwise people simply don’t take it. If the reduction in clinical symptoms is truly as good as the effects on the biological markers indicate, then Novartis could have a winner. Cautious optimism is definitely the right attitude, but with larger longitudinal studies potentially on the horizon, and given the right formulation, the new little pill may be the road to taking the wheeze out of asthma.
Adele Graham-King
Contributing Editor
Adele is a design consultant who works in product development for medical and healthcare applications. Her background is in pharma, and she has a degree in applied physiology.
