EmphyCorp has been granted Orphan Drug status by the FDA to develop N115 for the treatment of Interstitial Lung Disease. The intent of the Orphan Drug Act is to stimulate the research, development, and approval of products that treat rare diseases. Since the Orphan Drug Act passed, over 100 orphan drugs and biological products have been brought to market.
Interstitial Lung Disease (Diffuse), includes a number of rare conditions presenting with characteristic clusters of clinical features, marked by an immune response and containing an inflammatory component. This disease classification refers to a subset of approximately 130 to 2(X) rare pulmonary diseases that include the fibrosing lung diseases and the granulomatous diseases.
Interstitial lung diseases are typically characterized by a marked inflammation at the site of the lung injury. This inflammatory process leads to further destruction of surrounding healthy lung tissue, and a continuation and expansion of the sites of inflammation. This inflammatory process results in the production of reactive oxygen species, including superoxide anions and hydrogen peroxide, at the site of inflammation.
The functional changes reflect a restriction of airflow manifest by:
- Decreased vital capacity
- Decreased total lung capacity
- Decreased residual volume
- Decreased lung compliance
- Cyanosis (sign of severe hypoxemia; attributed to ventilation-perfusion mismatching)
- Late in the disease, one may see pulmonary hypertension due to destruction of the alveolar capillary bed
Nitric oxide is a known bronchodilator. It has been used successfully in this regard to treat patients with various pulmonary diseases, including the interstitial lung diseases. When endogenous nitric oxide, is exposed to oxygen radicals, it is converted to the toxic oxidant nitrogen dioxide, and its bronchodilating effect is mitigated. Conversely, nitrogen dioxide is a known deep lung irritant. It causes pulmonary inflammation; lowers levels of lung antioxidants; deteriorates respiratory defense mechanisms leading to increased susceptibility to respiratory pathogens and increased incidence and severity of respiratory infections; reduces lung function, and worsens asthma and COPD symptoms.
Reactive oxygen species, especially superoxide anions, are known to compromise lung function by increasing bronchoconstrictions. As a result of the increasing inflammation and the production of reactive oxygen species, and the decrease in nitric oxide that is believed to occur with the interstitial lung diseases, healthy tissue is damaged and lung function is compromised.
Based on our present understanding of the disease process involved with the interstitial lung diseases, and supported by the positive results obtained from the bleomycin-induced pulmonary fibrosis rat model study, it appears that an intervention in the inflammatory process that would result in a reduction in reactive oxygen species and a subsequent increase in nitric oxide could be an effective way to intervene in the disease process. This intervention would prevent the further spread of inflammation and lung damage caused by the production of reactive oxygen species, such as superoxide anions and hydrogen peroxide; and increase lung function by increasing bronchodilation.
Sodium pyruvate is a reactive oxygen species (ROS) antagonist that has been shown to neutralize oxygen radicals (specifically lowering the overproduction of superoxide anions), regulate the production and level of other inflammatory mediators, and regulate the synthesis of nitric oxide. Sodium pyruvate also increases cellular levels of glutathione, a major cellular antioxidant, which is reduced dramatically in antigen-induced lung disease patients.
The FDA has determined that N115 has sufficient safety toxicology and clinical data to proceed with the multi-dose, extended use, clinical trials. Phase III/Phase IV studies will focus on asthmatics and COPD patients. On the basis of existing clinical data, EmphyCorp is confident that its Investigative New Drug, N115, can and will be used for maintenance or continuous treatment of patients over extended periods of time. The Company believes that N115 will set the standard in the pharmaceutical industry for the treatment of major pulmonary diseases.