GlaxoSmithKline has not received the full backing it was hoping for from a US regulators’ panel to support its view that the highest dose of its asthma blockbuster Advair Diskus can increase survival rates for patients with chronic obstructive pulmonary disease.
A US Food and Drug Administration advisory committee voted 9 to 2 that the data presented did not provide substantial evidence to support the survival benefit for a 500/50 microgram dose of Advair/Seretide (fluticasone and salmeterol), although the panel did give a unanimous 11-0 backing to the claim that the drug at that high dosage demonstrated a significant reduction in the risk of exacerbations in patients with COPD, the fourth leading cause of death in the USA. Additionally, they voted unanimously that Advair 500/50 provides substantial advantages over salmeterol in treating the disease, also known as smoker’s cough.
This is a blow for GSK which had submitted data from three clinical trials to the FDA in support of the new indication for Advair, including the landmark study TORCH which involved over 6,110 patients. TORCH showed a 2.6% improvement in survival over three years among patients receiving Advair compared to placebo, but the FDA said that when looking at the USA alone, the survival benefit was 1.6%.
Statistical significance ‘narrowly missed’
The panel added that the increased survival data "narrowly missed" achieving statistical significance, saying that it would be misleading to include information from the study on the drug's label. It also suggested that a head-to-head comparison of the highest dose and the mid-strength (250/50) dose of Advair would be beneficial, and recommended additional data to better understand the increased incidence of pneumonia among COPD patients treated with inhaled corticosteroids. Advair 250/50 is already indicated in the USA as a maintenance treatment of airflow obstruction in patients with COPD associated with chronic bronchitis.
GSK put a brave face on the committee’s decision and Katharine Knobil, vice president of respiratory clinical development for COPD, said “we believe in the strength of the TORCH study and believe that the data show that Advair 500/50 provides important benefits for patients with COPD, including a reduction in the risk of dying. Therefore, we remain committed to working with the FDA as it reviews the supporting data from our clinical programme."
The agency usually follows the recommendations of its advisers, though it is not required to do so and a final decision is expected by August 11. Advair is GSK’s best-selling drug, with first-quarter revenues reaching £835 million (+11%) and this figure would be boosted if expanded use were granted. The highest dose currently costs over $225, almost 40% more than Advair 250/50, and Alexandra Hauber at Bear Stearns said in a recent note that approval of a higher dosage for COPD may add another 2%-3% to GSK’s earnings.