Last week's FDA advisory committee meeting on Victoza liraglutide from Novo Nordisk A/S took an unexpected turn, with a preclinical thyroid cancer signal rather than cardiovascular risk falling into place as the stumbling block on the path to an approval recommendation.
Going forward, Novo Nordisk's ability to get Victoza approved in the U.S. will depend on its ability to persuade FDA to overcome precedent by approving a compound that causes tumors in both genders of two species at exposure levels close to human dosing. The agency also must be convinced that elevated calcitonin seen in clinical trials of Victoza - a biomarker of thyroid C cell hyperplasia and medullary thyroid carcinoma - are not signs of a process that eventually will lead to cancer.
Novo had mixed success in persuading the Endocrinologic and Metabolic Drugs Advisory Committee on these points.
The company failed to convince panel members they could be certain the mechanism of action by which Victoza causes thyroid cancer in rodents is completely different from, and therefore is not relevant to, human effects.
The committee voted 12-1 that Novo had not demonstrated that the preclinical findings are not relevant to humans.
The committee voted 6-6, with one abstention, that available data on thyroid C cell tumors preclude marketing of Victoza.
The company was more successful at allaying questions about an imbalance in the number of patients who developed papillary thyroid cancer in its clinical trials, as well as concerns about the robustness of its data on cardiovascular risk.
The committee was convinced that screening for thyroid cancer prompted by the preclinical data led investigators to discover papillary thyroid cancers that were not caused by Victoza. It voted 12-0, with one abstention, that the papillary tumor data should not prevent marketing.
The vote on the CV issue was closer, with an 8-5 majority agreeing the sponsor had provided enough data to rule out an unacceptable risk. Novo committed to conduct a large post-market cardiovascular