Newly-presented data from a major clinical trial of GlaxoSmithKline's combination respiratory drug Advair/Seretide suggests that the treatment benefits patients with chronic obstructive pulmonary disease but falls short of statistically showing that it decreases the mortality rate.
The latest data on Advair (salmeterol and fluticasone), published by the New England Journal of Medicine, comes from GSK’s TORCH study which was conducted over three years in 42 countries with more than 6,100 patients aged 40 to 80 who suffered from moderate to severe COPD, the fourth leading cause of death in the western world. Patients were randomised into four treatment groups: 1,533 received fluticasone and salmeterol 500 mcg/50 mcg, 1,534 fluticasone,1,521 salmeterol,, and the remainder received a placebo.
GSK noted that Advair reduced the risk of death by 17.5% over three years compared to patients on placebo but this figure is not statistically significant. Researchers on the study, which was financed by the firm, suggest that the lack of statistical significance for the mortality endpoint is likely explained by the overall deaths in the study being less than expected. In addition, withdrawals from the placebo arm were especially high, as patients who left the trial were free to receive active treatment including Advair, but were counted as placebo patients in the final mortality analyses.
Nevertheless, GSK noted that Advair, when compared with placebo, also showed a 25% reduction in the rate of COPD exacerbations, which are a major cause of hospitalisation “and have significant physical and psychological effects on patients, many of whom never fully recover from the impact." Additionally, the study demonstrated that patients taking Advair experienced significantly improved lung function but it also showed that taking fluticasone by itself increased the risk of pneumonia.
Currently, the only treatments known to reduce the death rate in patients with COPD are oxygen therapy, smoking cessation and surgery to remove lung tissue and GSK noted that it has filed for approval to include the new data on the label with the US Food and Drug Administration. Advair sales grew 9% to £862 million in the fourth quarter and any favourable change to the label can only boost that figure.
GSK says Avandia linked to fractures in women
Meantime, GSK has informed doctors that long-term use of diabetes drug Avandia (rosiglitazone) has been linked to an increased incidence of fractures in women.
The company said that a review of safety data from the ADOPT study in 4,360 patients was generally consistent with the known safety profile of the drug, but significantly more female patients who received rosiglitazone experienced fractures than those who received either metformin or glyburide."
The fracture rate was 2.74 per 100 patient years for the 645 women treated with rosiglitazone versus 1.54 per 100 patient years for the 590 women in the metformin arm and 1.29 per 100 patient year for 605 women treated with glyburide.
Although there was an increase in fractures of the humerus, hand, and foot for women taking rosiglitazone, there was no increase in hip or spine fractures, which are common sites of osteoporotic fractures in postmenopausal women.
Following the review of ADOPT safety data, the company said it requested an independent safety committee review of fracture data from an ongoing rosiglitazone study, which was designed to evaluate cardiovascular safety of the drug.