Roflumilast: APTA 2217, B9302-107, BY 217, BYK 20869

Roflumilast [APTA 2217, B9302-107, BY 217, BYK 20869] is a selective phosphodiesterase IV inhibitor. It is being developed by Altana Pharma (formerly Byk Gulden), a subsidiary of Altana Group, as an orally administered therapy for asthma, chronic obstructive pulmonary disease (COPD), allergic rhinitis and psoriasis. The drug is awaiting regulatory approval in Europe for the treatment of asthma and COPD. Byk Gulden has stated that roflumilast relieves asthma symptoms through both an anti-inflammatory effect and a muscle relaxant effect. Roflumilast has potential as first-line long-term therapy in mild-to-moderate COPD and as additive long-term therapy in moderate-to-severe COPD. Altana has stated that roflumilast is to be marketed under the brand name Daxas. Altana Group and Pharmacia Corporation (now Pfizer) signed an agreement on 22 April 2002 to collaborate on the development and commercialisation of roflumilast for the treatment of respiratory disorders, including asthma and COPD. The companies will jointly develop the drug for the US, Europe and other markets. Pharmacia will co-ordinate development in the US and Altana will co-ordinate development in Europe. After approval of the drug, Pharmacia and Altana will jointly launch and promote roflumilast in the US, Europe and elsewhere. Altana will receive an upfront payment and additional milestone payments. Altana additionally has the option to co-promote Pharmacia products in the US and elsewhere. On 16 April 2003, Pharmacia Corporation was acquired by, and merged into, Pfizer. In November 2002, Altana and Tanabe Seiyaku signed an agreement to collaborate on the development and commercialisation of roflumilast for the treatment of respiratory diseases, including asthma and COPD. Tanabe Seiyaku and Altana will develop roflumilast for asthma and COPD in Japan, and will jointly launch and co-promote roflumilast in Japan following regulatory approval. Roflumilast has been in multinational phase III clinical studies in Europe for the treatment of asthma and COPD. In September 2003, Altana announced the completion of a phase III trial in COPD in more than 1400 patients; the trial showed positive results. In the US, roflumilast is in phase III trials for the treatment of asthma and phase II trials for the treatment of COPD. Phase I clinical trials of roflumilast were begun in Japan by Tanabe Seiyaku in the fourth quarter of 2003. Altana has stated that roflumilast has shown significant superiority over placebo in the treatment of asthma in phase II trials. The efficacy of the drug appears to be comparable to low-dose inhaled corticosteroids in the treatment of asthma and at least equal to inhaled corticosteroids in the treatment of COPD. Altana Group presented data from phase II trials in 516 patients with COPD at an analyst meeting [August 2001, Bad Homburg, Germany] that showed that roflumilast 500 microg/day significantly improved FEV(1) at 24 weeks compared with placebo. In March 2004, Altana Pharma presented pharmacokinetic data from a phase I trial of roflumilast at the 60th Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI-2004) [San Francisco, CA, USA]. This open-label, randomised, two-period crossover study investigated the pharmacokinetics of oral roflumilast and its active metabolite, roflumilast N-oxide, among 12 healthy male subjects. Participants received single doses of oral roflumilast 500 microg and intravenous (i.v) roflumilast 150 microg as a 15-min short-term infusion. In November 2002, the combined global market for asthma and COPD products was estimated to be worth >11 billion US dollars. In Japan, products in this market segment reached sales of approximately 1.5 billion US dollars in 2001. Roflumilast has patent protection in Europe and Japan until 2014 and in the US until 2015. The Financial Times in April 2002 claimed that roflumilast is an 'important' product for Altana, due to be listed on the New York Stock Exchange later in the same month. The Altana chairman confirmed that the company had been in talks with Pfizer, Bristol-Myers Squibb and Novartis with regard to future development and commercialisation of roflumilast. In September 2002, Dow Jones Newswires stated that Altana is to file for European approval of roflumilast 1 year later than initially was expected; however, this has not changed the company's outlook for the product, which was said to remain at at 1 billion Euros. In August 2001, the Financial Times reported that roflumilast, for the indication of smoker's cough alone, has the potential to reach sales of more than 500 million US dollars a year. A future co-marketing deal for roflumilast in the US was said to be "a key step towards expanding Altana's presence in the US".