The Swiss firm Actelion Ltd. submitted the non-clinical and production sections of its NDA to the FDA for its lead drug, bosentan, in pulmonary hypertension, and it aims to bring the product to market before the end of next year.
"We expect to launch bosentan in pulmonary hypertension in October or November 2001," said company spokeswoman Annette Kraehenmann.
Bosentan, which Allschwil-based Actelion originally in-licensed from F. Hoffmann-La Roche Ltd., of Basel, also is in Phase III trials for congestive heart failure. Kraehenmann said the company expects to launch this treatment by mid-2002. The company anticipates combined revenues of around CHF 400 million (US$232 million) to CHF 500 million for these two indications in the U.S. and Europe.
It is also developing bosentan for a number of additional conditions, which could yield further revenue. The most advanced is in Phase II trials.
Actelion positions bosentan as the first orally active endothelin receptor antagonist. Its first Phase III trial in pulmonary hypertension, which involved 32 patients, yielded very positive results, according to Kraehenmann. "Ability to exercise and basically the whole hemodynamic spectrum, has been improved significantly," she said. The clinical data will be presented at the American Heart Association meeting in New Orleans next month. Recruitment for an expanded Phase III trial, which will include 150 patients, commenced in July. About one-quarter of the total cohort has been enrolled.
The company is likely to adopt a dual marketing strategy for the drug, to take account of the different patient populations it is addressing - it estimates that bosentan can be taken by about 100,000 pulmonary hypertension patients, whereas congestive heart failure affects around 10 million people. "We are quite convinced of the idea that we can market bosentan in pulmonary hypertension ourselves," said Kraehenmann. "For bosentan in congestive heart failure we would probably choose a partner."
In pulmonary hypertension, bosentan will go head to head with Uniprost from United Therapeutics Corp., of Silver Spring, Md., which is also in the process of undergoing an NDA filing. However, Uniprost is delivered subcutaneously, rather than orally. The currently available treatment, London-based Glaxo Wellcome plc's formulation of epoprostenol (Flolan), requires continuous intravenous infusion.
Actelion's second compound, the acute heart failure treatment tezosentan, is currently at the Phase III stage also and is the subject of a co-development and co-promotion agreement in the U.S. with Genentech Inc., of South San Francisco. The company also has a drug discovery alliance in an undisclosed area with Johnson & Johnson, of New Brunswick, N.J., and has additional programs in cancer, Alzheimer's disease, obesity, malaria and inflammation.
Actelion has performed strongly since its debut on the New Market of the Swiss Stock Exchange in April. Its market capitalization has increased by 198.5 percent to CHF 3.7 billion (based on its share price during trading Monday) since its IPO. The company launched a secondary offering of shares Monday, although it will not gain any proceeds from this transaction. Existing shareholders, including venture capital investors and management, are offering around 10 percent of the company's stock in a combined public offering in Switzerland and a private placing with international institutional investors. Credit Suisse First Boston and Morgan Stanley Dean Witter are leading a banking consortium that is managing the sale.