NovoNordisk is facing a much easier path for Victoza (liraglutide) in Europe than the rocky road the type 2 diabetes therapy is on in the U.S.

On April 23, Victozagarnered a recommendation for approval from the European Medicines Agency. The actual approval from the European Commission should follow in about two months. With that in hand, Novo will begin selling Victoza in various European markets over the summer.

The GLP-1 agonist has faced a more challenging reception in the U.S. The predictable roadblock was the cardiovascular safety profile, given FDA's new policy on CV risk assessment for type 2 diabetes drugs. At the April 2 advisory committee review, though the drug passed by an 8-5 vote, the panel felt the CV questions couldn't be answered with the data in hand (see ¹ Also see "Diabetes Drug Developers Urged To Study Higher Risk Patients By FDA Panel" - Pink Sheet, 27 April, 2009.).

But the committee also focused on an unexpected safety issue that may pose a more significant regulatory hurdle - a higher rate of thyroid c-cell tumors in rodents (² Also see "Liraglutide Cancer Signal Puts Agency In Uncharted Review Territory" - Pink Sheet, 13 April, 2009., p. 19).

The European regulators, however, appear to agree with Novo's R&D chief Mads Thomsen that "the mechanism [behind the raised incidence of thyroid c-cell tumors] is one that mice and rats are sensitive to, but that monkeys and humans are not."

The Novo exec did stress the thyroid cancer signal is a GLP-1 class effect, but the mechanism is only relevant in rodents. No problems have been detected with the only approved GLP-1 drug, Lilly/Amylin's Byetta (exenatide). Roche is moving ahead with its GLP-1 agonist taspoglutide despite the class concern; no signs of carcinomas have been seen in Roche's rat and mouse studies, but there have been adenomas (³ Also see "Roche Forges Ahead With Taspoglutide Despite Cancer Signal With Competitor GLP-1" - Pink Sheet, 16 April, 2009.).

The European label for Victoza does mention the preclinical thyroid c-cell carcinoma findings, Thomsen said, but other than that, the EMEA is not seeking any other interventions. The regulators haven't even requested that the company take any additional measures - such as thyroid cancer screening - to rule out potential risk.

"There are no restrictions on usage" as a result of the preclinical thyroid cancer data, he stated. "It was a clean approval."

This unrestricted European endorsement is important for more than just Victoza's EU commercial potential. China, for instance - where Novo is building a strong presence - requires a sponsor to have home-market approval before it can even submit a new therapy. There are also spill-over effects for other markets, Thomsen commented, since "some countries simply base their approval decisions on the European outcome."

Chances in the U.S., however, look less positive, based on the split panel outcome. FDA is due to decide whether to approve liraglutide late next month.

Analysts, including Matthew Osborne at Lazard Capital Markets, reckon that the best case would be a launch in the second half of the year but with a black box warning and/or monitoring for thyroid cancer. Other options include a 6-12 month delay due to a request for additional data, or outright rejection.

- Melanie Senior (m.senior@elsevier.com)

Victoza Clears European Regulators Without Thyroid Cancer Restrictions

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