FDA panel knocks back inhaled cyclosporine on efficacy question
cyclosporine has been deemed safe by a US Food and Drug
Administration advisory committee, but the jury is still out over
the efficacy of the treatment, reports Phil Taylor.
The panel was not asked to vote on approval of the new product, developed by Chiron and called Pulminiq, but its failure to back the efficacy of the drug reduces the chance that the FDA will give the green-light to the treatment, which is being developed for use in preventing rejection in lung transplant patients. The FDA is not obliged to follow the advisory committee's advice, but usually does.
Cyclosporine has been a key drug in the prevention of rejection in patients undergoing transplants for 20 years, and to date is approved for use in kidney, heart and liver transplant patients. Chiron's application for Pulminiq is aiming to get approval for the use of the drug, alongside standard immunosuppressive therapy, to improve survival and cut rejection in lung transplant patients.
Although lung transplants are much less common than other organ transplants, there is a significant unmet medical need as more than half of patients undergoing this procedure who reject their donated lungs die. Transplant specialists mix up their own inhaled formulations of cyclosporine to try to improve matters, but if approved Pulminiq would be the first commercial, clinically-proven preparation available. This unmet need is witnessed by the fact that Pulminiq has been granted priority review status, giving it a six-month FDA review period.
Chiron's own studies suggest that on top of standard therapy, Pulminiq achieved a 79 per cent decrease in the risk of death and a 72 per cent decrease in the risk of chronic rejection or death for patients compared to patients receiving placebo. But earlier this year the FDA requested additional analysis of the pivotal study, extending the priority review period, and giving the first indication that the application might not run smoothly.
The panel's concerns seem to relate to matters raised in FDA documents - published ahead of the meeting - suggesting that Pulminiq was unable to show a significant impact on episodes of acute rejection, and statements that the balance of the patient populations in Chiron's trial could have been off, skewing the results. There were eight votes in favour of Pulminiq's efficacy, and eight against.
Approximately 1,100 lung transplants are performed each year in the US but only 45 per cent of lung transplant recipients will be alive after five years, compared to 70 to 90 per cent of heart, kidney and liver transplant recipients.
Chiron acquired exclusive worldwide commercial development and marketing rights for Pulminiq from Novartis in April 2003. The company is now expecting a definitive FDA decision on the application by the middle of next month.
