A US Food and Drug Administration advisory committee has said that Novartis will have to carry out additional clinical studies before it could recommend its immunosuppressant Certican (everolimus) for use as prophylaxis against acute rejection in heart transplant recipients.
A majority of the panel agreed that Certican has demonstrated superior efficacy to azathioprine in the prevention of acute rejection. However, voting went against recommending approval – by seven votes to six – as some panelists felt that more data was needed on the safety of the proposed regimen, which combines Certican with cyclosporine.
A dose monitoring study should be undertaken, said the committee, and include lower doses of cyclosporine to see if it is possible to minimize the risk of renal toxicity sometimes seen in trials of the regimen.
Novartis said it has already started further studies in heart transplantation using Certican in combination with reduced dose cyclosporine and therapeutic drug monitoring to supplement the existing clinical registration database from over 3,000 heart and kidney transplant recipients worldwide. An on-going European post-marketing study in heart transplantation - which may be available for review in 2007 - might address the committee's concerns, it suggested.
Certican was approved in Europe to prevent acute rejection in both heart and kidney transplant patients in 2003, and it is registered for this use in 48 countries outside the USA. The FDA first asked for additional clinical data on the drug in 2003, so the further delay is a real disappointment to Novartis.
The Swiss company needs to accelerate the take-up of Certican to support its transplantation franchise, for years driven by its Sandimmun and Neoral brands of cyclosporine but now being hit by generic competition.