The FDA Pulmonary-Allergy Drugs Advisory Committee (PADAC) voted 9-3 to recommend approval of Esbiet® (pirfenidone) developed by the biotech firm Intermune (ITMN) for idiopathic pulmonary fibrosis (IPF). The same drug is approved in Japan for IPF and sold under the trade name Pirespa® by Shionogi in that country. Both Intermune and Shionogi had licensed pirfenidone from Marnac and its co-licensor, KDL GmbH. Intermune got the rights to sell the compound in the United States, Europe and other territories except in Japan, Taiwan and South Korea, and Shionogi & Co. Ltd. Got the right for Japan.
Pirfenidone is an orally active small molecule drug that may inhibit collagen synthesis, down regulate production of multiple cytokines and block fibroblast proliferation and stimulation in response to cytokines. Pirfenidone has demonstrated activity in multiple fibrotic conditions, including those of the lung, kidney and liver.
IPF is a deadly disease with disabling symptoms that include progressive dyspnea (difficulty breathing), cough, clubbing of fingers, fatigue and rales (a crackling sound in the lungs during inhalation). The symptoms and findings are not exclusive to IFP, but present in many other lung diseases. IPF is characterized by abnormal and excessive deposition of collagen in the pulmonary interstitium (mainly the walls of the alveoli) causing inflammation and scarring. with inflammation. Attributing the lung fibrosis to cigarette smoking, gastroesophageal reflux disease and autoimmune disorders could not be proven, as many IPF patients never smoked and do not suffer from gastro-esophageal reflux disease, or autoimmune disease.
Before the FDA Committee voted in favor of the drug, it was very difficult for analysts to rationally speculate over the drug’s outcome. Pulmonary fibrosis is a chronic progressive disease that kills patients in three to five years. No medication has succeeded in preventing its progression and deadly outcome. As the term idiopathic implies, the cause of IPF is still unknown and the disease seems to have multiple etiologies. No one drug can benefit all patients with such a disease, and no clinical lab tests or any other diagnostic procedures could be used to recruit the patients who would respond to the drug. As a result, an effective investigational drug given to the wrong patients would unfairly end up with bad statistics and denial of approval. Moreover, no scientists expect fibrosis to respond to any treatment in sight. They believe that drugs that might ease the symptoms would fail to show improvement on a CT scan. As a matter of fact, the most optimistic pulmonologist believe that, with the poor information in hand about the disease, drug developers’ utmost ambition would be to develop products that can ease the harsh symptoms, or at best prevent the worsening of the disease.
We believe that Intermune’s drug Esbiet® has realized the two objectives and that the FDA will approve it. In favor of the drug approval is the fact that it has been approved and marketed in Japan since 2008. The Japanese experience confirmed the drug has better safety profile than the non specific anti-inflammatory and immunosuppressive drugs that were used in Japan before Pirespa® (the trade name of pirfenidone in Japan was approved and is currently been used in the U.S.
The market for the Intermune version of the drug is large with approximately 500,000 patients in the U.S., Europe and all the other territories excluding Japan, Taiwan and South Korea.
In addition to pirfenidone, Intermune has a HCV protease inhibitor drug in phase 2 trials. It also has a second-generation HCV protease inhibitor and pirfenidone analogue in preclinical trials. As the money will fill Intermune coffers, the firm will definitely acquire excellent products and expand its pipeline.