Daxas (roflumilast), partnered with Pfizer, reaches the submission stage a little later than expected - it was originally scheduled for filing in December - but remains well ahead of the competition in this new therapeutic class.
Its nearest rival is GlaxoSmithKline's Ariflo (cilomilast), which was turned down by a US Food and Drug Administration (FDA) advisory panel last year, likely delaying the programme for one to two years, while a Phase II candidate developed by Celltech and Merck & Co was also discontinued in 2003.
The PDE-4 inhibitors have been notoriously hard to develop, with many of the early compounds entered into development dropped from development because of side effects, particularly nausea but also serious adverse such as ischaemic colitis.
Theoretically, a PDE-4 inhibitor should act as a more effective at blocking the activity of inflammatory mediators (leukotrienes) than existing drugs, such as Merck & Co's Singulair (montelukast) and AstraZeneca's Accolate (zafirlukast).
However, until recently the narrow therapeutic index has muted enthusiasm for the use of PDE-4 inhibitors in asthma, for which there are a lot of effective medications.
Nevertheless, results presented at the 2003 European Respiratory Society annual conference have revealed that Daxas is much safer than previous PDE-4 inhibitors.
Consequently, if the drug is approved and accepted by the medical community, Daxas has the potential to be a blockbuster.
According to market research firm Datamonitor, Daxas is predicted to reach peak global annual sales of $1.2 billion (€950m).
Daxas is likely to have a strong uptake as it will be the first in its class to reach the market and Pfizer's marketing power will ensure the drug is propelled to reach its maximum potential.
Furthermore, Pfizer's plans for the COPD market received a boost earlier in February when the FDA approved Spiriva (tiotropium), a drug with a different mechanism of action (acting as an M1 muscarinic receptor inhibitor) that was originally developed by Boehringer Ingelheim.
According to IMS statistics, the current annual global market for COPD drugs is worth about $3 billion, possibly tripling to over $9 billion by 2010, as safer and more convenient therapies for this mainly smoking related disease are introduced.
The disease is treated with a number of asthma drugs, but 2002 saw a shift in attitude with the launch of Spiriva, the first product to be specifically developed and indicated for COPD.
Spiriva sales have already exceeded Pfizer and BI's expectations, and it looks set to become a blockbuster with sales in excess of $1 billion.
Other drugs in the pipeline for COPD, according to IMS, include: ONO 6126: a PDE-4 inhibitor from Ono, in Phase II trials; talnetant: a tachykinin (neurokinin 3) antagonist, which started Phase II trials in 2002 with GSK; 842470/AWD 12281: originally developed by Viatris, this PDE-4 inhibitor is being developed by elbion, which granted GSK worldwide development and commercialisation rights in July 2002.
Phase I trials in COPD are underway; IC 485: Phase II trials are scheduled for the third quarter of 2003 for this PDE-4 inhibitor, in development with ICOS; and CP 671305: a PDE-4 inhibitor in Phase I trials with Pfizer for COPD.