- Amylin and JDRF announced that they would explore the feasibility of co-formulating pramlintide (Amylin’s Symlin) with insulin to treat type 1 diabetes.
Earlier this week, Amylin and JDRF announced that they would explore the feasibility of co-formulating pramlintide (Amylin’s Symlin) with insulin to treat type 1 diabetes, as part of JDRF’s Industry Discovery and Development Partnership (IDDP). This would involve combining Symlin and insulin into one mealtime injection, as opposed to the separate injections currently required. According to Amylin and JDRF, co-formulation studies will require up to three clinical proof-of-concept studies, which will determine the optimal pramlintide:insulin ratio and investigate whether this fixed ratio can improve glucose control compared to insulin alone. As we understand it, these three studies are feasibility trials; additional studies will need to be conducted before regulatory approval. It remains unclear which mealtime insulin will be used, although as we understand it, the proof-of-concept studies are expected to begin in 2Q11 and last “up to” four years (the clinical studies are not yet listed in clinicaltrials.gov). As a reminder, Symlin is approved for type 1 and type 2 diabetes patients using mealtime insulin therapy who have failed to achieve desired glucose control despite optimal insulin therapy (with or without concurrent sulfonylurea and/or metformin in type 2 patients). Symlin requires an additional injection and according to the Symlin label, the pharmacokinetic characteristics are altered when mixed with regular insulin, NPH, and 70/30 premixed formulations of human insulin immediately before injection. Currently, we believe Symlin is not widely used because of the additional required mealtime injection and the difficulties associated with dosing, which cause side effects of nausea and insulin-induced hypoglycemia if not titrated properly. Although a single-injection co-formulation would solve the hassle of the additional injection, it will be important for Amylin to determine a ratio of the two hormones that does not further complicate dosing of Symlin, since the combination product will have a fixed amount of Symlin for a given amount of insulin (i.e. they will presumably not be able to be individually titrated).
Symlin primarily works through three mechanisms: 1) slowing the rate of gastric emptying; 2) suppressing the release of post-prandial glucagon; and 3) enhancing satiety (ultimately decreasing caloric intake and causing modest weight loss). While a co-formulated therapy may better mimic the physiological action of beta cells, there are currently no data to prove this hypothesis. As we understand it, roughly 60% of lives are currently covered for Symlin at a tier 2 benefit. If positive results are obtained, we are curious whether Amylin will plan to pursue this combination for type 2 patients on basal-bolus insulin, especially since 60% of roughly 150,000 current Symlin users are estimated to be type 2.
Close Concerns Questions for Amylin/JDRF
What is the design of the proof-of-concept clinical studies?
What bolus insulin will be used in the trials?
Wil all rapid-acting analogs potentially compatible for co-formulation with Symlin?
--by Sanjay Trehan and Kelly Close