Roche is moving ahead with its glucagen-like peptide-1 analog taspoglutide despite reports of adenomas (benign tumors) in animal studies and the stumbling block Novo Nordisk hit with its competing type 2 diabetes product Victoza (liraglutide) due to a thyroid cancer signal in animals.

Taspoglutide is currently being studied in Phase III trials, with data expected by the end of the year. Carcinogenicity data is also expected later this year.

Management updated investors on the status of the investigational drug during a first quarter sales and earnings conference call April 16 after FDA's Endocrinologic and Metabolic Drugs Advisory Committee issued a split decision on the safety of Victoza earlier this month due to the cancer signal.

A rare type of thyroid tumor (thyroid C cell carcinoma) was seen in both rat and mouse models with liraglutide at clinical exposure levels ¹ Also see "No Victory For Victoza: FDA Panel Splits On Whether Cancer Signal Should Block Approval" - Pink Sheet, 2 April, 2009.).

In contrast, Roche said it has not seen any carcinoma in rat or mouse studies involving taspoglutide, although there have been cases of adenomas in both species.

"It is our profound belief that this is rat-specific, it is species-specific, and the reason for this is that there is a very high expression of GLP-1 receptors in the thyroid glands of rodents compared to the low level in humans," Pharma CEO William Burns said during the conference call.

As a precaution, Roche's Phase II studies for taspoglutide were designed to measure calcitonin levels as a marker. Calcitonin is a hormone produced by C-cells in the thyroid glands. In that regard, the studies showed there is "absolutely nothing to worry about," Burns said.

"We also decided that we would include it in the Phase III tracking, so we will have the answer to this question in several thousand patients for the FDA, and we do not think this is in any way a rat on the shoulders for taspoglutide," the exec maintained.

Additionally, Roche cautioned against viewing all GLP-1 products as the same, noting that the molecules in development across the industry are "quite different." There is currently only one approved GLP-1 analog, Lilly/Amylin's Byetta (exenatide), for which there has been no cancer signal detected.

Roche Steps Up CV Emphasis In Diabetes Drugs

Given FDA's current focus on the cardiovascular safety of diabetes drugs, Roche said it is taking a harder look at the cardiovascular safety profile of taspoglutide and the data that will be needed to meet FDA's requirements. A big concern for diabetes drug developers is FDA's concerns with cardiovascular safety and how the agency's new guidance on the issue, released in December, will impact drug reviews and approvals (² Also see "FDA’s Diabetes Guidance On CV Risk Will Get First Test With Pending NDAs" - Pink Sheet, 22 December, 2008., p. 25).

"From the cardiovascular risk side, this molecule should actually be a positive contributor because of the weight loss, so we do believe that we are building on a fairly strong foundation on that dimension," Burns said.

With FDA's emphasis on cardiovascular safety, Roche is taking a hard-line approach across its metabolic portfolio, prioritizing drugs based upon their cardiovascular risk reduction and weight loss potential, not only glucose lowering benefits, he indicated.

"There is a growing understanding that perhaps glucose control in type 2 diabetes may not be the only answer," Burns explained. "We need to make sure that there are other important benefits for the patient in addition to HbA1c reduction."

Along with taspoglutide, the two other diabetes drugs that have been deemed high priority in Roche's pipeline are the peroxisome proliferator-activated receptor alpha gamma agonist aleglitazar and a sodium glucose transport-2 inhibitor, R7201, licensed from Japanese subsidiary Chugai, both in Phase II.

On aleglitazar, Roche is talking with opinion leaders and regulatory authorities about study designs and positioning of the drug going forward.

"What we've been working on here is do we go the classic anti-diabetic route, HbA1c with added benefits, [or] do we take an alternative approach, which is more of the cardiovascular risk profile for a sub-defined group of patients, for example post-[acute coronary syndrome]," Burns said.

With the SGLT-2 candidate, Roche is profiling the drug not only on HbA1c measurements, but also cardiovascular risk reduction and weight loss. As part of the portfolio review, Roche has discontinued development of its dipeptidyl peptidase-IV inhibitor and glucokinase inhibitors.

Roche's first quarter pharmaceutical sales grew 8 percent to $8.01 billion (CHF 1=$0.87), driven by sales of the cancer drugs Avastin , Herceptin and Rituxan . Consolidated sales increased 7 percent to $10.1 billion.

-Jessica Merrill (j.merrill@elsevier.com)

Roche Forges Ahead With Taspoglutide Despite Cancer Signal With Competitor GLP-1

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