Nycomed & Merck fail to convince NICE about Daxas in COPD
This article was originally published in Scrip
Draft guidance from NICE is recommending that Nycomed and Merck provide evidence of how Daxas roflumilast performs in its likely clinical setting as an add-on to conventional therapies of chronic obstructive pulmonary disorder (COPD). NICE's appraisal committee says there is great uncertainty about the effect of roflumilast on reducing the rate of exacerbations as an add-on to triple or dual therapy for people with severe COPD. There was also some question of whether trials of roflumilast were conducted against appropriate comparators such as theophylline.
Triple therapy involves long-acting muscarinic antagonists (LAMA) plus long-acting beta-2 agonists (LABA) plus inhaled corticosteroids (ICS). Dual therapy involves a LAMA plus LABA for those people who are intolerant to, or decline, ICS. Theophylline is an option for people with severe COPD – defined as forced expiratory volume in one second (FEV1) post-bronchodilator less than 50% predicted – who have had a trial of short-acting bronchodilators and long-acting bronchodilators, or who cannot use inhaled therapy.
Roflumilast is an orally administered long-acting selective phosphodiesterase-4 (PDE4) inhibitor which targets cells and mediators in the body believed to be important in COPD. The compound is approved as Daxas in the European Union and Canada as Daliresp in the US. Nycomed, the Swiss company which is being acquired Takeda Pharmaceutical, granted exclusive UK commercialisation rights to Merck & Co.
The committee considered clinical evidence from six trials in which roflumilast was compared with placebo and said it was satisfied that there was eividence that the drug reduced exacerbations. However, the committee also discussed its likely use in clinical practice and noted that there was no hard evidence of what happened when the drug was used as an add on therapy.
"Without any direct trial evidence for roflumilast in the anticipated in the treatment pathway, it was not possible to know whether the treatment effect of roflumilast was additive and consistent across all treatment combinations," noted the agency.
"As there was great uncertainty about how well the treatment works alongside triple therapy, the committee could not establish that it would be good value for money. As a result, the committee discussed whether it was appropriate to recommend the set up of a research trial to determine the clinical effectiveness of roflumilast on top of triple or dual therapy," added NICE Health Technology Evaluation Centre director Professor Carole Longson.
The committee did think that there is a reasonable prospect of providing benefits to people with COPD in a cost-effective way but that the uncertainty surrounding the treatment effect meant that more robust evidence of the benefits of roflumilast as an add-on to triple or dual therapy would be needed
The draft guidance recommends setting up a trial to assess its clinical effectiveness as an add-on for triple therapy of LAMA plus LABA/ICS or dual therapy (LAMA plus LABA) and compared with theophylline in those patients in which that drug would be suitable.
Noting that Nycomed is conducting the REACT study to assess roflumilast on exacerbation rates when added to LABA/ICS, the committee concluded that the company could feasibly set up and pay for (including the cost of the drug) a new trial to study the effect of roflumilast on exacaberation rates on top of triple therapy and dual therapy if the person is intolerant to, or declines, ICS, and compared with theophylline as appropriate.
So far, NICE is saying that roflumilast should be recommended only in the context of research as part of a clinical trial for adults with severe COPD associated with chronic bronchitis with a history of frequent exacerbations as an add-on to bronchodilator treatment.
Stakeholders have until 30 September to respond to NICE's consultation on the draft guidance. NICE anticipates being able to issue final guidance in January 2012.