Unit Dose Budesonide (UDB) for the
Treatment of Pediatric Asthma
MAP Pharmaceuticals is developing Unit Dose Budesonide (UDB) as a potential treatment for pediatric asthma in children from 12 months to eight years of age. UDB is an inhaled corticosteroid (ICS) designed to be administered more quickly and to provide efficacy at a lower dose than conventional nebulized budesonide that is currently on the market. Budesonide has been used for more than 20 years with demonstrated safety and efficacy. Conventional nebulized budesonide is the only ICS approved by the FDA for treating asthmatic children under the age of four. In our Phase 2 clinical trial, UDB reduced symptoms of asthma at a dose approximately half that of the current treatment. We initiated a Phase 3 clinical trial of UDB in January 2008.
Pediatric Asthma: A Global Public Health Problem
According to the Centers for Disease Control and Prevention (CDC), pediatric asthma is the most common chronic childhood disease in the United States, and is a major global public health problem. Asthma is a chronic respiratory disorder characterized by inflammation and narrowing of the airways, leading to limitation or obstruction of airflow and resulting in symptoms such as wheezing, chest tightness, breathlessness and coughing. According to the CDC, approximately 1.2 million children four years of age and under in the United States suffer from asthma.
Limitations of Current Nebulized Therapies
Due to its safety relative to other corticosteroids, budesonide has been widely used to treat pediatric asthma. The Global Initiative for Asthma and the National Asthma Education and Prevention Program both recommend ICS as the preferred initial treatment for controlling asthma in children of all ages. However, conventional nebulized budesonide has three major limitations:
- Lengthy administration time for delivery of therapeutic dose: Administration of an effective dose of conventional nebulized budesonide is relatively slow, with a published nebulization time in clinical use of five to ten minutes. However, our own market research indicates that nebulization times can often be between ten and 15 minutes. We believe the lengthy administration process may limit compliance to the prescribed therapy.
- Delivery of therapeutic dose late in the administration cycle: In our research, much of the conventional nebulized budesonide dose is delivered late in the administration cycle, because a smaller percentage of drug is nebulized in the first few minutes of administration. This late, or delayed, delivery in an already lengthy administration cycle can exacerbate poor patient compliance, particularly for young children who may be unlikely to complete a full administration cycle, and reduces the likelihood of a restless toddler receiving a therapeutic dose.
- Potential side effects associated with local and systemic exposure:During conventional nebulized budesonide administration, drug often adheres to the back of the mouth and throat, and can lead to local side effects, such as cough, hoarseness and oral thrush. Excessive systemic exposure to the drug can lead to cortisol suppression, which has been associated with impaired growth in children, reduction in bone density, skin thinning and bruising.
Our Potential Solution: Unit Dose Budesonide
We use our proprietary technologies to develop UDB as a small, uniformly sized budesonide particle. The small size and stability of these drug particles allow for more of them to be transported into the lung by the small droplets generated by the nebulizer. The result is a formulation that exhibits a consistent, linear delivery of therapy over the entire administration time. Based on our clinical studies, we believe UDB may provide patients with the following therapeutic benefits when compared to conventional nebulized budesonide:
- Faster delivery: In our Phase 2 clinical trial, complete nebulization of UDB occurred in an average of three to five minutes. This faster delivery time may mean more convenience for parents, who administer the therapy twice a day. Additionally, restless toddlers are more likely to receive a therapeutic dose more often, potentially resulting in better asthma control and a reduction in emergency room visits.
- Higher percentage of drug delivered earlier: Smaller particles allow more consistent and linear dosing in a shorter administration cycle. In our research, the small size of UDB particles resulted in approximately twice as much UDB being nebulized in the first two minutes compared to conventional nebulized budesonide.
- Efficient delivery at a lower dose: Our Phase 2 trial showed that UDB has the potential to treat asthma effectively with approximately half the lowest dose of conventional nebulized budesonide. There were no incidences of oral thrush, and there was no reduction in cortisol levels.