BIOCHAPERONE® PRAMLINTIDE INSULIN (BC PRAM INS)
BIOCHAPERONE® PRAMLINTIDE INSULIN: MULTI-HORMONAL PRANDIAL COMBINATIONS FOR THE TREATMENT OF TYPE 1 DIABETES
High-performance, easy-to-use multi-hormone therapy to improve long-term outcomes
Although insulin is a vital treatment for people with type 1 diabetes, even the best-controlled patients present significant glycemic variations and frequently do not achieve the targets set by their physician. This may result in an increase in the risk of severe complications in the long term, such as cardiovascular disease, retinopathy, renal failure and neuropathy.
In fact, in people who do not have diabetes, insulin is secreted synchronously and acts in synergy with other hormones, such as amylin and GLP-1, to control glycemia. In type 1 diabetes, ultimately, neither insulin nor amylin are secreted, and GLP-1 secretion is deficient. It is therefore possible that the use of insulin alone cannot address all the metabolic deficiencies related to diabetes.
Pramlintide (Symlin®, AstraZeneca), a rapid-acting amylin analog, was approved in 2005 for the treatment of diabetes (type 1 and 2) as a supplement to intensive insulin therapy. In Phase 3 clinical studies, this molecule has been shown, when used as a supplement to insulin therapy, to improve HbA1c and reduce prandial insulin use and weight gain compared to insulin alone.
Unfortunately, to the extent that insulin therapy for type 1 diabetes requires high patient compliance, with frequent glycemia monitoring and at least four injections of insulin daily, the introduction of an additional injectable treatment is often synonymous with a significant deterioration in quality of life and an increase in the cost of treatment, which can lead to its abandonment.
The combination of pramlintide with insulin could therefore prove to be an elegant solution to maximize the medical benefit whilst maintaining patient compliance and controlling health costs. Developing such a combination is Adocia’s objective for the BioChaperone Pramlintide Insulin program.
Currently, the prandial insulin and pramlintide formulations are not compatible. Adocia has therefore used its expertise to develop BioChaperone® molecules that can solubilize and stabilize pramlintide in a neutral pH solution, enabling it to be combined with prandial insulin.
Our BioChaperone® formulation strategy, based on previous clinical results from the co-administration of pramlintide and prandial insulin showing a clear medical benefit when hormones are administered separately, could reduce development time. The BioChaperone Pramlintide Insulin project could also support a competitive pricing strategy, taking advantage of proteins already approved and in the public domain.
BIOCHAPERONE® PRAMLINTIDE INSULIN: MAIN CLINICAL RESULTS
In September 5th, 2018: Adocia announced positive pharmacodynamic and safety topline results from the Phase 1 study of BioChaperone® Pramlintide Insulin , the ready-to-use co-formulation of pramlintide and human insulin. In this study, BioChaperone Pramlintide Insulin (pramlintide and recombinant human insulin) showed a significant 97% decrease in blood glucose excursion over the first two hours after the meal compared to Humalog® (prandial insulin lispro, Eli Lilly). BioChaperone Pramlintide Insulin also showed similar glucose control over the first two hours after the meal compared to separate injections of Symlin® and Humulin®. All treatments were well tolerated.
“These are encouraging results, confirming that a co-formulation of pramlintide with human insulin can reproduce the marked reduction of postprandial glucose shown in previous studies of pramlintide and insulin given separately,” said Dr. Matthew Riddle, Professor of Medicine, Oregon Health & Science University, Division of Endocrinology, Diabetes, & Clinical Nutrition. “By mimicking the normal co-secretion of amylin and insulin with meals, this 2-in-1 combination has the potential to address the persisting unmet need for mealtime glucose control for people with diabetes.”
Based on these very promising first clinical results, Adocia intends to intend the next clinical trial in H1 2019.
REFERENCES & PUBLICATIONS
Communication at major conferences
- “BioChaperone® Technology Enables the Development of Pramlintide-Prandial Insulin Combinations” (Oral Presentation n°349-OR) presented by Dr. Grégory Meiffren, 78th Scientific Sessions American Diabetes Association, 22 -26 June 2018, Orlando, Florida (USA).
- “BioChaperone technology enables the development of pramlintide-prandial insulin combinations” (Poster 811) presented by Dr. Rémi Soula, 53rd Annual Meeting of the European Association for the Study of Diabetes, 11-15 September 2017, Lisbon (Portugal).