Dermatology leaders rallied to the defence of Novartis' Elidel (pimecrolimus), a topical cream for atopic eczema, this week during the 8th Congress of the European Society for Pediatric Dermatology in Budapest. Elidel, along with Fujisawa’s Protopic ointment (tacrolimus), which is in the same class of topical calcineurin inhibitors, has been threatened with a US Food and Drug Administration black box warning of a potential cancer risk.
Professor Johannes Ring, President of the European Academy of Dermatology and Venereology and Dr Ramon Grimalt, General Secretary of the ESPD said the FDA’s concerns about cancer were purely theoretical.
"There is no clinical evidence whatsoever to support this warning. We think it is disproportionate and unjustified," said Professor Ring. "We are upset because we don’t want this to limit access to the drugs or cause unnecessary anxiety to patients or their caregivers." Health authorities should not be swayed by theoretical risks, he added, but base decisions to allow prescribing of TCIs on proper evidence-based risk/benefit reviews.
A recommendation to include a black box warning was made by the FDA's Pediatric Advisory Committee in February and was repeated on an FDA website in March [[11/03/05a]]. In the US especially, where lawyers advertise widely for potential product liability victims, the news has already alarmed patients despite the black box not yet having appeared on the product label because the company has not yet agreed the box wording with the FDA. Meanwhile, numerous dermatology physician and patients’ organisations have been issuing strong statements criticising the FDA and reassuring doctors and patients of the products' safety record.
Since launch, Elidel has been used by over five million patients, half of them children under 10, and Protopic by 2.5 million. In addition, 19,000 people have been studied in Elidel clinical trials, including 7,000 children and 3,000 infants. So far, fewer cancers have occurred among patients than the incidence rate among the general population and these were unrelated to drug treatment. Novartis has a registry of 4,000 patients who will be closely monitored for up to 10 years.
The FDA’s concerns stem from the drugs’ immune-suppressing action. Oral immunosuppressant drugs such as oral steroids and oral calcineurin inhibitors used in transplant patients have been associated with an increased risk of lymphoma. However, topical TCIs are not absorbed into the bloodstream so have no systemic effects. Research on animals showed doses more than 27 times higher than the maximum recommended human dose produced malignancies, but this was with oral versions or experimental topical formulations that were specially designed to penetrate the dermis.
Elidel made net sales of $349 million in 2004.