Here is the relevant portion of the conference that describes, at least from the speakers information, the stark differences between Byetta and its more thyroid-cancerous prone peer:
Now, before I highlight the regulatory progress to the plan submission for exenatide once weekly, I want to provide perspective on the recent advisory panel for the liraglutide. Keep in mind that in Amylin, we are grounded in science, science is our strength. We have been investigating the GLP-1 area since 1996 and we established ourselves as leaders in 2005, when we launched BYETTA with our partner Eli Lilly.
At the recent FDA Advisory Committee meeting concern was raised regarding a preclinical cancer finding in the liraglutide development program particularly malignant C-cell carcinoma of the thyroid.
Let me first highlight, what we know. Currently, there is no clinical evidence that thyroid cancer of any type is a GLP-1 class effect. The discussions at the recent Advisory Committee meeting highlighted that risk benefit considerations are key for any potential therapeutic agents.
Drugs within the same class often have distinct efficacy and safety profiles due to differences in structure, mechanism of action and metabolism. Within the area of diabetes, we have three distinct examples. First, the biguinides where you can contrast phenformin with metformin, the thiozolidinedione class where you can contrast Actos with Avandia, and with resilient and the DPP-4 inhibitor class where you can contrast Januvia with [galvas].
Regarding efficacy, BYETTA and liraglutide appear to have similar results in terms of both glucose and late lowering FX. Yet BYETTA has no preclinical signals of cancer, but instead had established a well documented safety profile. BYETTA has been used in more than 1 million patients with over 7 million prescriptions written since introduction to the market. BYETTA and liraglutide are distinct molecules with significant differences in structure and metabolism.
BYETTA is not a GLP-1 analog instead BYETTA is a synthetic provision of a naturally occurring peptide that function as GLP-1 receptor agonists. BYETTA achieves clinical efficacy at much smaller doses of peptide and liraglutide. BYETTA is administered at low doses 5 or 10 micrograms and largely cleared intact through a well characterized renal elimination pathway. Liraglutide is administered at high milligram doses of peptide and circulates at high concentrations in the blood stream.
To achieve clinical outcomes similar to those achieved with BYETTA, first a patient must be exposed to approximately 90 to 100 or more liraglutide per day based on a weight basis of the drug. The drug substance that is administered the greater the potential for undesired for half target effects. The regulated bricks down into metabolite that circulate in the blood stream, the effects of these biologically active bi-products are not well characterized.
BYETTA has a different more typical peptide construct and is cleared largely intact by the kidneys and then fully eliminated from the body. In carcinogenicity studies, liraglutide was associated with increased malignant C-cell cancers in both males and females and rats and mice. In addition, the significant increases in malignant progress are commerce of the scan was seen in male mice.
Now, let’s focus on BYETTA. BYETTA is the only GLP-1 receptor agonist currently available for clinical use offering powerful sustained A1C reductions with weight loss. There is no limit association with evaluate C-cell carcinoma and BYETTA based upon preclinical trial data and post marketing surveillance data. Preclinical findings are outlined in the prescribing information for BYETTA.
To summarize, in BYETTA preclinical studies, beanie thyroid tumors were observed in female rats at all exenatide doses in a two year study. No tumors were observed in male rats or mice of either sex. For BYETTA, extensive clinical studies as well as post marketing data do not suggest an association of thyroid tumors of any type. As of 30 September, 2008 experience of BYETTA included more than 5500 subjects exposed in clinical trials with greater than 4600 total subject years of exposure.
Some advisory panel members questioned, there was a concern about thyroid cancer might apply to BYETTA. In response the questions of the post meeting press conference a senior FDA official stated that “the agency looked back at the clinical data for BYETTA and didn’t see any thyroid cancer risk and the agency so for hasn’t detected an increased risk and looking at post marketing data” but also said there are limited data to the preventively rollout it possible increased risk.
Now let me help you understand, what this data means to once we got. If approved exenatide once weekly will be the first once a week therapy for the treatment of type 2 diabetes. It has the potential of significantly advancing the treatment of type 2 diabetes as demonstrated by efficacy data from DURATION-1 and DURATION-2 studies and its novel once weekly administration.
In these comparative studies the exenatide once weekly as demonstrated a greater glucose lowering effect than three recently approved widely used medication for type 2 diabetes namely Actos, BYETTA and Januvia. In the preclinical program a two year study in rats employing three doses of exenatide once weekly demonstrating a finding similar to that seeing in the BYETTA program, an increase incidence of benign thyroid tumors called C-cell adenomas.
These tumors were observed in both males and females. In this study C-cell carcinoma a slow growing malignant tumor is also seen. While observe at all doses in both males and females the incidence of these malignant tumors was significantly increased only in female rats treated with the highest doses, the doses that provided tissue exposure approximately 30 times that seen with the intended human doses. Again I want to emphasis that the apples ability of these findings to human diseases has not been clearly established.
In addition no evidence of C-cell cancers received during exposure in primates in studies that extended over 11 months, that no time during either the BYETTA or exenatide once weekly program that malignant fibrosarcomas been seen this contrast to the liraglutide program.
Is it spin? Is it wishful thinking? Is it semantics? I am pleased to see management tackle this issue head on with confidence and information.
Tinker
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