NPC Archive Item: FDA rejects application for roflumilast in COPD, but previous CHMP positive opinion

NOTE – This is an archive post from the NPC and has not been updated since first publication. Therefore, some hyperlinks may no longer be working.
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24 June 2010

The FDA has recently rejected a New Drug Application for roflumilast (Daxas®), which was in licensing to reduce exacerbations associated with chronic obstructive pulmonary disease (COPD). Further clinical trial work has not been requested, but additional information and analyses are required

Roflumilast recently received a Postive Opinion from the European Medicines Agency and is likely to be marketed in the near future. Currently no timeline for NICE guidance has been proposed. The place of roflumilast in the management of patients with COPD is uncertain. Commissioners may wish to bear this in mind when engaging with clinical specialists and local decision-making bodies to identify the patients for whom roflumilast may be appropriate and agree a local policy.

Roflumilast is an oral once-daily phosphodiesterase 4 enzyme inhibitor, that received a Positive Opinion, from the European Committee for Medicinal Products for Human Use (CHMP), in April 2010 for maintenance treatment of severe COPD (FEV1 post-bronchodilator less than 50% predicted) associated with chronic bronchitis in adult patients with a history of frequent exacerbations as add on to bronchodilator treatment. A pharmacovigilance plan will be implemented as part of the marketing authorisation.

We recently reviewed the four key studies that formed the basis of the European licence application and have provided further information in our On the Horizon bulletin. Patients participating in the trials were described as having “bronchitic symptoms” defined by chronic cough and sputum production. Therefore, only these specific patients should be considered for treatment.

The studies did not provide information about whether roflumilast (in addition to inhaled bronchodilator treatment) provides any significant benefit when used instead of, or in addition to, an ICS. Many patients in the trials were already receiving an ICS prior to enrolment, which was discontinued; therefore it is not possible to extrapolate the results of these trials to patients in the real world.

Adverse effects associated with roflumilast included weight loss, diarrhoea and nausea.

Roflumilast has not been considered in the updated NICE COPD clinical guideline, which is due for publication in June 2010, but is in the list of proposed topics for a technology appraisal.

Information on the management of COPD is available on the approriate respiratory section of NPC.

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