Double trouble hits Altana respiratory pipeline
SummaryAltana has announced the delay of its US application for Daxas until late 2005 due to clinical trial enrolment taking longer than originally anticipated. The news will be of further concern to the company's investors, coming on the back of the recent announcement that another of its respiratory drugs, Alvesco, failed to win full FDA approval.
Daxas is Altana's selective phosphodiesterase-4 (PDE-IV) inhibitor that is being investigated as a treatment for asthma and chronic obstructive pulmonary disease (COPD) in partnership with Pfizer the and .
Altana confirmed earlier this year that a US 12-month long-term efficacy study in COPD was still in the recruiting phase, which is likely to be the 1,100-patient OPUS study that will determine the effect of Daxas (roflumilast) in the treatment of exacerbations (an acute worsening of respiratory symptoms). According to the National Institutes of Health clinical trials database, the study started in October 2003 and is estimated for completion in July 2005.
One setback after another
Daxas was filed with the European Agency for the Evaluation of Medicinal Products in February 2004, using the centralized approval system. The EU submission only included six-month data from the pivotal "Record" study. Thus, while Altana could have filed for approval with the six month data in the , it appears it is taking a more cautious approach, possibly in view of the negative FDA advisory panel decision on GSK's PDE-IV Ariflo (cilomilast) in 2003.
The panel said that Ariflo's new drug application did not provide enough long-term efficacy data to warrant approval. Datamonitor expects the launch of Daxas to come during the second half of 2006, with peak sales of $500 million.
The Daxas delay is not the only recent setback to the German group's respiratory pipeline. Prior to the delay of its US Daxas application, Altana announced that it had received an approvable letter from the FDA for Alvesco (ciclesonide) for the treatment of asthma in adults, adolescents and children of four years of age and older.
Alvesco is an inhaled corticosteroid with novel release and distribution properties, developed by Altana and co-marketed in the with Sanofi-Aventis. Ciclesonide's novel properties result in a lower incidence of side effects, demonstrated by measurements of the hypothalamic-pituitary-adrenal axis, against current brand leaders, GSK's Flixotide and AstraZeneca's Pulmicort.
Counting on Alvesco
The specific clinical data requests outlined in the letter have not been disclosed, although they may be related to lens opacity ocular events that occurred in a US Phase III trial. Concurrent with the submission in December 2003, Sanofi-Aventis initiated a Phase IIIb, 12-month trial to further profile the safety of high doses of Alvesco in moderate to severe asthma to characterize the occurrence of lens opacity ocular events.
One of Alvesco's potential advantages over existing corticosteroid treatments is its favorable safety profile. In April 2004, Altana received approval in the for Alvesco, with a starting dose of 160mcg once daily, which is also the maximum dose. The company did not gain approval for the higher 400mcg dose, although they did gain Australian marketing approval in February 2004 for a daily dose of up to 320mcg.
By not gaining initial approval for higher dosages in , Alvesco's advantages are much reduced, as patients requiring high-dose ICS have the greatest risk of adverse effects.
While there seems to be little to suggest that the challenges facing both Alvesco and Daxas will not be resolved eventually, Altana will certainly be hoping that there are no further setbacks in the approval process to give investors any greater cause for concern.