Unmet Business and Medical Needs
An Unmet Business Need
Lung disease is a significant problem, and it is getting bigger. Currently,
lung disorders rank as the fourth leading cause of death in the US behind
heart disease, cancer, and cardiovascular disease, and it is the only major
disease that continues to show a substantial increase in mortality rates
each year. Between 1979-1998, mortality from lung disease almost
doubled. Although the mortality rate remains much higher in men than
women, it is rising even faster in women. According to the World Health
Organization, by the year 2020, lung disease is expected to rise to the
third leading cause of death in the US and other developed nations.
Compelling Economic Factors
Lung disease is an enormous economic burden to society. It strikes
during the height of the productive years, significantly interferes with the
ability to earn a living, forces many to go on Medicare disability or take
retirement at an early age, and often disrupts the lives of the individual
and family for many years before death occurs. According to data from
the NHLBI, the direct costs of health care services and indirect costs
related to loss of productivity for lung disease was $26 billion in 1998
and $30.4 billion in 2000 (with up to $17.5 billion spent worldwide on
therapeutic agents alone). Medical expenses for COPD patients alone
are high because of frequent visits to the emergency room, extended
hospital stays, and expensive medications. In 1997, there were an
estimated 13.4 million physician office visits and more than 600,000
hospitalizations for these patients. Data from the Centers for Disease
Control indicate that diseases of the respiratory system rank third in the
number of emergency room visits. It is expected that all of the costs
associated with fibrotic lung disease will continue to spiral upward
because the prevalence is continuing to rise each year (NHLBI, 2001).
An Unmet Medical Need
There are only a few treatment options that are currently available to the
millions of patients who suffer from fibrotic lung diseases. Once the
diagnosis has been established, the aims of treatment are to alleviate
symptoms, prevent progression of disease and preserve optimum lung
function to improve performance of daily activities, and enhance quality
of life.
Current Therapies
Chronic progressive lung diseases that have a significant fibrotic
component are typically treated by agents known to enhance lung
function (primarily by reducing constriction of the lung airways through
bronchodilation) as well as agents to reduce inflammation (examples are
noted in the table on the following page).
Bronchodilator therapy
The rationale behind the use of bronchodilator agents in the treatment of
lung disorders is based on their ability to increase airway size. The
expiratory airflow limitation in lung disease is due to a narrowing of the
airways caused by chronic inflammation, hypertrophy of the airway
smooth muscle, and enlargement of the bronchial mucus glands. The
bronchoconstriction found in asthma patients is mainly located in small
airways and can be reversible, and that found in COPD patients is
usually in the medium sized airways and is considered irreversible.
Beta agonists
ß2-adrenoceptor agonists are the most common of the prescribed
medication in respiratory disease. They are used in the treatment of
asthma and the reversible element of airway obstruction commonly found
in patients with lung disease. Although there are several different types of
ß2-agonist, most are pharmacologically similar and all are used in a
similar fashion.
Anticholinergics
The anticholinergic agents produce bronchodilation by a different
mechanism than the ß2-agonists. For example, ipratropium is a non-
selective competitive muscarinic acetylcholine receptor antagonist. When
given intravenously, these drugs inhibit bronchial receptors, and minimal
effects on cardiac receptors.
Methylxanthines (theophylline)
Theophylline has bronchodilator properties and is used in the treatment of
asthma and fibrotic lung disorders. Theophylline works as a
bronchodilator by the relaxation of bronchial smooth muscle, and may
also have some anti-inflammatory activity. The usefulness of
theophylline, however, is limited by the high incidence of side effects and
it’s narrow therapeutic index.
Corticosteroids
Inhaled corticosteroids are now standard therapy in the management of
inflammation with asthma and some conditions related to COPD.
Inhaled steroids as well as oral dose formulations are currently used.
The LINC Approach to Improved Efficacy
Unlike the currently available therapies that only limit the severity of
symptoms and dampen the progression of the disorder, the LINC
technology will offer the field a unique approach for directly treating
scarring fibrosis, one of the primary causes of functional lung loss and
associated decrease in quality of life.
The LINC technology represents a new paradigm in the treatment of
fibrotic disease by PTHrP agonists/agonists as well as downstream steps
that may be modulated by the PPAR system. This unique approach will
extend the use of these medical technologies to new and challenging
disease states in the pulmonary care field, as well as to other indications
where tissue fibrosis contributes to the disease process.
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