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The chase for the cure

The following article appeared on the Coalition for Pulmonary Fibrosis Web site. I thought it was a very nice summary of some of the major developments in pulmonary fibrosis research in the last year as well as what's on the horizon in the next year or two.

Sometimes it amazes me how far we've come just in the six years since I learned I had HPS.


CPF Chairman Marvin Schwarz, MD Discusses IPF Research with BioWorld Today Reporter

Rare Pulmonary Fibrosis may Have Blockbuster Potential By Catherine Hollingsworth, BioWorld Today

A handful of companies are working to develop a treatment for a rare lung disorder called pulmonary fibrosis that, by some estimates, could present a $500 million to $1.5 billion market opportunity.


"It is probably a commercially significant market," said Michael Gilman, CEO of Stromedix Inc., whose company has a compound for pulmonary fibrosis in Phase I.

Aside from the sales potential, a drug targeting the fatal lung-scarring condition also would improve the care of patients who currently have no approved treatments.

Pulmonary fibrosis is a disease that leads to worsening shortness of breath, until patients eventually suffocate. Patients suffering from the disease usually live an average of three to five years, according to the California-based Coalition for Pulmonary Fibrosis and other sources. In fact, many people with cancer often live longer than those diagnosed with pulmonary fibrosis.

An estimated 128,000 Americans are affected by pulmonary fibrosis, and an estimated 48,000 new cases develop each year, according to the coalition.

A few companies - Japanese drugmaker Shionogi & Co. Ltd., U.S. biotech InterMune Inc., and Swiss biotech Actelion Ltd. - are out front in developing potential new treatments for patients with idiopathic pulmonary fibrosis (IPF), a form of the disease in which the cause is unknown.

Shionogi has filed for approval of its IPF drug candidate pirfenidone in Japan and is awaiting a final decision. Brisbane, Calif.-based InterMune Inc., which holds rights to pirfenidone in the U.S. and Europe, has completed two large Phase III studies and plans to initiate an extension study. Swiss biotech Actelion also has an experimental IPF drug, bosentan (Tracleer), in Phase III testing, with results expected in 2009.
Several other companies - Amgen Inc., Wyeth, Boehringer Ingelheim GmbH, Novartis AG, Genzyme Corp., and Pipex Pharmaceuticals Inc. - have earlier stage compounds intended for the treatment of pulmonary fibrosis.

Currently, InterMune's Actimmune is prescribed off-label to treat IPF, though the off-label use has steadily declined in recent years in light of two negative studies, said analyst Howard Liang, of Leerink Swann & Co.

According to Liang's figures, U.S. sales of Actimmune were $107 million in 2005 and declined to $90 million in 2006 due to the unfavorable IPF data. In 2007, sales slid further, totaling $53 million, due to a second negative trial in that indication, Liang said.

In March 2007, InterMune halted further Phase III testing of Actimmune in IPF after an independent data monitoring board found a lack of survival benefit compared to placebo.

To date, the most successful treatment available for IPF patients is lung transplantation, said Dr. Marvin Schwarz, board chairman of the Coalition for Pulmonary Fibrosis. But he said many patients who are eventually diagnosed with IPF are older and often are not eligible for lung transplants due to comorbidities such as diabetes or cancer.
Other drugs that have been tried in the past for IPF, such as corticosteroids and immunosuppressants for lung cancer, have not been sufficiently effective, Schwarz said.

However, he noted that many drug companies now are taking an interest in the disease and are exploring a number of pathways to target the disease. Some are focusing on interferon gamma and tumor necrosis factor-alpha to address the uncontrolled scarring in the lungs, while others have focused on the beta pathway to slow the progression of the disease, said Schwarz, who recently received the top honor given by the American Thoracic Society and the American Lung Association for his career accomplishments in pulmonary medicine.

In addition, the National Institutes of Health established an IPF network of medical centers that are focused on IPF research.

InterMune spokesman Jim Goff said high dropout rates in IPF patients and tolerability issues have been a challenge for conducting studies in that population. In addition, he noted that it is a tough disease to study, on the level of some forms of cancer. But he said InterMune was encouraged by the Shionogi Phase III trial results that showed a 44 percent decline in the rate of lung function. InterMune's Phase III program is similar to Shionogi's in that both companies are seeking to slow the decline in lung function. However, Goff said, the InterMune study is of longer duration and has a larger patient enrollment.
Goff agreed that IPF represents a "potentially large market opportunity from a financial standpoint."

Schwarz said it is possible that a treatment for IPF likely will have broader applications in treating other forms of fibrosis affecting the liver, kidney, eye and skin, for example. The final pathway in uncontrolled fibrosis, he said, appears to be similar across those different forms of fibrosis.

It is not unheard of for a rare disease that affects a relatively small number of people to approach blockbuster status, Liang said. He pointed to Novartis' Gleevec for chronic myeloid leukemia, a drug with $3 billion in sales; and Genzyme, a company with products focused on rare diseases.

Any IPF treatment is expected to have a high price tag, Liang said, based on the cost of other pulmonary drugs and the $50,000 cost of Actimmune.

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