Reading the April 21 warning letter from the FDA to Novartis is a bit like reading a primer on hownot to promote one's drug on the Internet. Where to begin? Well, Novartis was tagged by the FDA after its DDMAC division reviewed two web sites - gistalliance.com and cmlalliance.com - which were sponsored by the drugmaker, but are now out of commission.
The problem? The web sites don't mention the Gleevec cancer drug by name, but come close enough to ruffle the FDA. In effect, these disease awareness sites came off as so-called product branded sites. And so the agency writes these were "false and misleading because they promote the drug for an unapproved use, fail to disclose the risks associated with the use of Gleevec and make unsubstantiated dosing claims, (which) can put patients at higher risk of experiencing adverse events." Moreover, the materials placed on the site weren't submitted to the FDA at least 30 days prior to dissemination or submitted on the appropriate form as required by law.
Gleevec is approved to treat chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GIST), and the letter spells out the approved uses and dosaging, along with a host of violations, which the FDA describes as so "serious" that it demands "a comprehensive plan of action to disseminate truthful, nonmisleading, and complete corrective messages about the issues" cited in the warning letter. The FDA also warns Novartis about another site - bloodleveltesting.com. Here are some of the problems:
• The websites discuss the use of tyrosine kinase inhibitors (TKIs) for the first line treatment of GIST and CML, often in conjunction with the Novartis name. Gleevec is the only tyrosine kinase inhibitor (TKI) indicated for first-line treatment of chronic phase CML; the only TKI indicated for first line treatment of GIST; and the only TKI made by Novartis that is indicated for both GIST and CML. These product details are wellknown in the oncology community.
• The websites contain numerous references to the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology, which recommend the use of Gleevec exclusively for the first-line treatment of CML and GIST.
• The websites are perceptually similar to the Novartis Gleevec product website, incorporating similar color schemes (including a distinct orange), design layouts and other presentation elements.
• The websites are clearly marked with the Novartis Oncology name and logo and/or the Novartis name and logo and discuss sponsorship by Novartis Pharmaceuticals Corporation.
• The healthcare professional-directed “Targeting BCR-ABL” webpage on the CML Alliance website provides a direct link to the Novartis Gleevec product website in reference to first-line therapy for CML, while the consumer-directed version of this page provides a link to the Novartis-sponsored “My CML Circle Program” website, which discusses Gleevec as a treatment for CML.
• The websites are registered to Novartis AG.
• The websites present data from imatinib clinical studies, and provide the corresponding literature references, which include the drug name in the listed publication titles. At least one of the publications4 recounts the pivotal clinical trial submitted to FDA in support of the approval of Gleevec in the treatment of adjuvant GIST.