Liraglutide cancer risk

[chantell.reagan]

During the September 2009 Webinar, the following question was submitted and we’d like to open it for a general discussion in our community:

"Can you tell us more about the cancer risk with liraglutide?"

[chantell.reagan]

In early April 2009, the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee reviewed liraglutide. As part of the safety review, the committee evaluated the following thyroid cancer risk flags described in the Novo Nordisk submission:

·In rodent studies, benign and malignant thyroid C-cell tumors were observed (related to medullary thyroid cancer which is very rare and takes years to develop in humans)
·In non-human primate studies, C-cell proliferation was not observed
·In human clinical studies, 6 cases of C-cell hyperplasia were reported (with similar incidence rates between liraglutide and the comparator). In addition, papillary thyroid cancer cases (a more common type of thyroid cancer) were also reported

The big dilemma confronting the committee was that due to the natural progression of medullary thyroid cancer it would be very difficult to rule out that liraglutide increases the risk of this cancer. Of note, Novo Nordisk apparently has additional 2-year completed human studies looking at 1500 patients where there was no risk of increased thyroid cancer rates seen in the data.

In a split-vote decision, here’s how the committee voted in terms of this risk:

·The committee voted 12-1 that animal C-cell tumor findings from liraglutide treatment were relevant to human beings
·The committee vote was split 6-6 with one abstention with regards to whether available data on thyroid C-cell tumors should permit marketing of the drug
·The committee voted 12-0 with one abstention that available papillary thyroid cancer data permits marketing of liraglutide, with the assumption that the remainder of the risk/benefit data are acceptable

Some experts believe that c-cell proliferation could be a class effect with the GLP-1 analogues. In a follow-up commentary (post FDA advisory meeting), one expert from the NIH stated "It certainly sounded from what I heard today that this may be a class effect for any of the longer-acting agents" [i.e. long acting-Byetta]. Conversely, Amylin maintains that there is no link between "thyroid C-cell carcinoma and [Byetta] based upon clinical trial and post-marketing data."

It remains to be seen how the FDA will rule on liraglutide.

Sources:
Novo Nordisk press release 4/09
Briefing documents for FDA’s Endocrinologic and Metabolic Drugs Advisory Committee meeting 4/09: liraglutide
Endocrine Today news article 4/09
Forbes news article 4/09