Nycomed, Forest lung drug shows add-on potential

* 17 pct reduction in exacerbations with Daxas monotherapy

* Further lung function improvement if added to other drugs

* Oral drug seen used alongside existing bronchodilators

* Daxas may reach market in 2010, if approved by regulators

By Ben Hirschler

LONDON, Aug 28 (Reuters) - An experimental once-daily tablet from Nycomed [NYCMD.UL] and Forest Laboratories FRX.N improves lung function in people with "smoker's lung" and may be a useful add-on to conventional inhaled drugs, experts said on Friday.

Privately owned Swiss drugmaker Nycomed, which is working towards a multibillion-dollar flotation, hopes Daxas will reach the market in 2010 and believes it has blockbuster potential.

It signed a deal earlier this month with Forest, giving the U.S. group rights to sell the drug in the United States as a treatment for chronic obstructive pulmonary disease (COPD).

Some analysts, however, have been wary of prospects for Daxas, given its troubled history and the failure of other drugs that work in a similar way, by inhibiting a enzyme called PDE4 linked to inflammation.

When used on its own, Daxas reduced exacerbations, or COPD attacks, that required medical intervention by 17 percent per patient per year compared with a placebo, according to results of two Phase III trial reported in the Lancet medical journal.

The drug, known generically as roflumilast, also increased by 48 millilitres the volume of air that patients would breath out in one second, a measure known as FEV1.

“It met our expectations and compares very favourably with other drug trials,” researcher Klaus Rabe of the Leiden University Medical Centre in the Netherlands told reporters.

Still, the reduction in exacerbations came in at the lower end of what had been expected by analysts at Cowen, who had been looking for an 18 to 25 percent improvement.

The effect will inevitably be compared with other COPD medicines, notably Boehringer Ingelheim and Pfizer's PFE.N Spiriva, which showed a 21 percent reduction in exacerbation risk in clinical tests, according to a Boehringer spokeswoman.


In practice, Daxas is likely to be used alongside existing inhaled treatments, since two other trials published in the Lancet found it had a clear additional benefits when given with Spiriva and GlaxoSmithKline's GSK.L salmeterol.

“It will definitely be used on top of existing medication because the unmet need is not to replace existing medication but to provide additional benefit,” said Leonardo Fabbri of Italy’s University of Modena and Reggio Emilia.

Nycomed had said in October Daxas was effective in the four Phase III trials but gave no details at the time.

PDE4 inhibitors are known to be associated with side effects -- notably diarrhoea, nausea, weight loss and headaches -- and the latest Daxas trials recorded adverse events in 67 percent of patients on the drug versus 62 percent for the placebo group.

“There is a proportion of 10 to 15 percent of patients who may not tolerate this drug,” said Fabbri.

Nycomed has already submitted Daxas to European and U.S. regulators for approval and it hopes for registration in both jurisdictions next year.

Industry analysts believe an approval is by no means assured, given the history of the medicine. Daxas failed to show adequate benefit in an earlier clinical trial, prompting Pfizer to hand back rights to the product in 2005 to Altana ALTG.DE, which then owned it.

In addition, the record of other PDE4 drugs in lung disease is not good. Glaxo scrapped a similar drug called Ariflo in 2007, while Forest and Glenmark GLEN.BO said last week oglemilast had failed in mid-stage Phase II tests.

Still, Daxas has progressed further than any other PDE4 in lung disease and Forest hopes it will help fill a revenue gap when the blockbuster antidepressant Lexapro, sold with Lundbeck LUN.CO, loses patent cover in 2012. (Editing by David Holmes)