BIOCHAPERONE® COMBO

A more effective two-in-one insulin product

combo

Currently available insulin intensification options are either complex or produce suboptimal medical results

Today, 50% patients on basal insulin do not reach adequate glycemic control (Sanofi’s Q3 2015 Presentation).

To improve glycemic control, insulin treatment intensification for type 2 diabetic patients usually requires the addition of prandial insulin to an existing basal regimen. The combined use of a prandial and a basal is called the “basal/bolus” regimen. This regimen complicates treatment as it necessitates two different insulin products, and requires patients to pay close attention to injection timing and the injected dose. Importantly, it dramatically raises the shot burden for patients, increasing the number of daily injections from 1 to 2, 3 or 4.

When patients have difficulty with the basal/bolus regimen, they are usually eligible for premixed insulin. Premixed insulin is a fixed combination of a soluble fraction and a precipitated fraction of the same rapid-acting insulin (analog or human), usually injected twice-a-day. However, premixed insulins do not offer ideal medical performance because of a delayed and prolonged prandial action, a basal action profile shorter than 24 hours, and an elevated risk of hypoglycemia.

 

Insulin combos may be a simple and efficient solution providing both fasting and prandial coverage

For a long time, it was technically impossible to truly combine gold-standard long-acting insulin glargine with a rapid-acting insulin in the same product, as they could not be formulated in the same pH ranges.

Using BioChaperone, Adocia has developed BioChaperone Combo, a true combination of insulin glargine (Lantus®, Sanofi), the gold standard basal insulin, with a rapid insulin analog, insulin lispro (Humalog®, Eli Lilly). The aim of BioChaperone® Combo is to improve patient options and outcomes by developing an insulin product combining the relative ease-of-use and simplicity of a premixed insulin regimen with the tighter, more physiological control of a basal/bolus regimen.

Image basal Insulin and insulin combinations

 

Adocia believes that an insulin combo, by providing true basal and prandial coverage, could become the new algorithm for treatment intensification. Patients could intensify their treatment form basal while staying on a single-injection, single-product treatment (Combo once-a-day), and if disease progresses, simply add another injection of the same product (Combo twice-a-day).

 

BioChaperone® Combo has been successfully tested in three clinical trials

Phase I/II PK/PD clinical study in type 1 diabetic patients

In this proof of concept study, BioChaperone® Combo demonstrated significantly faster prandial action compared to Humalog MixTM in type 1 diabetic patients.

 

In addition, BioChaperone® Combo also offered a full-day of basal coverage equivalent, to Lantus®.

 

Glucose infusion rate

These clinical results were presented at two significant diabetes congresses in 2014: ADA and EASD.

2014-congres

 

Adocia initiated and successfully completed two additional phase I/II clinical studies in 2015

Meal tolerance test against an insulin analog premix in type 1 diabetic patients.
Topline results from the meal tolerance test against an insulin analog premix in type 1 diabetic patients were announced in November 2015.

The study, comparing the effect on post-meal glycemic control of individualized doses of BioChaperone Combo and Humalog® Mix75/25™ (Eli Lilly) injected at the beginning of standardized meals, met its primary endpoint, demonstrating superiority of BioChaperone Combo in the reduction of post-meal blood glucose over the first two hours (Delta-AUC-BG(0-2h)) compared to Humalog® Mix75/25™. In this study, BioChaperone Combo was shown to be superior to Humalog® Mix75/25™ on these two criteria, consistent with tighter blood glucose control:

– BioChaperone Combo was associated with significantly lower blood glucose excursions in the first two hours vs. Humalog® Mix75/25™ (primary endpoint, Delta-AUC-BG(0-2h)= 89.2 ± 48.6 mg*h/dL vs 117.7 ± 47.6 mg*h/dL, p=0.0078). This result is confirmed by a reduction of the maximum blood glucose level of 23 mg/dL (BGmax: ratio = 0.9; p=0.0003).

– The minimum blood glucose level observed during the period with BioChaperone Combo was also significantly better controlled than with Humalog® Mix75/25™ (BGmin: ratio = 1.3; p=0.0030). While this study was not designed to measure differences in hypoglycaemia between both treated groups, a lower number of hypoglycaemic events was observed with Biochaperone Combo vs. Humalog® Mix75/25™.

Detailed results of this trial have been submitted for publication at the American Diabetes Association’s 76th Scientific Sessions in June 2016.

 

Euglycemic clamp study against basal/bolus and an insulin analog premix in type 2 diabetic patients

Topline results from the euglycemic clamp study against basal bolus and an insulin analog premix in type 2 diabetic patients were published in November 2015.

The study was designed to compare the pharmacodynamic profile of BioChaperone Combo (single dose of 0.8 U/kg) to that of Humalog Mix75/25 (Eli Lilly, single dose of 0.8 U/kg) and of the separate and simultaneous injections of Lantus® (insulin glargine, Sanofi, single dose of 0.6 U/kg) and Humalog® (insulin lispro, Eli Lilly, single dose of 0.2 U/kg). The two key parameters for this comparison were the early prandial effect (AUCGIR(0-2h)) and the late basal effect (AUC GIR(24-30h)) of the three treatments.

Based on these two parameters, BioChaperone Combo was found to be significantly superior to Humalog Mix75/25 and exhibited no difference compared to the separate injections of Lantus and Humalog.

 

Detailed results of this trial have been submitted for publication at the American Diabetes Association’s 76th Scientific Sessions in June 2016.

 

In September 20th, 2016, Adocia launched a new clinical study of BioChaperone® Combo.

This study aims to measure the effect of BioChaperone® Combo injected at mealtime on post-meal glycemic control in subjects with type 2 diabetes compared to that of premix insulin Humalog® Mix25TM (Eli Lilly) and the separate injection of Lantus® (Sanofi) and Humalog® (Eli Lilly).

Click here to read the press release: Combo New study

These studies will prepare the dossier for Phase III testing.

 

 On June 6th, 2017, Adocia Announced Positive Topline Results from a Meal-Test Clinical Study of BioChaperone® Combo in People with Type 2 Diabetes

BioChaperone® Combo demonstrated a statistically significant 18% reduction in blood glucose excursion over the first two hours after the meal compared to Humalog® Mix25TM. The number of hypoglycemic events per patient was also significantly lower with BioChaperone Combo than with Humalog® Mix25TM.

BioChaperone Combo resulted in postprandial glucose control which was at least as good as that achieved with separate simultaneous injections of Lantus® and Humalog® with a similar number of hypoglycemic events per patient.

Click here to read the press release

 

 On June 7th, 2017, Adocia Initiated a Phase 1b Clinical Study on the  Dose-Proportionality of BioChaperone® Combo in  People with Type 2 Diabetes

This study aims to document the dose exposure of BioChaperone Combo across three different doses in people with type 2 diabetes in order to assess dose-proportionality.

Study results are expected in Q4 2017.

Click here to read the press release

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