BIOCHAPERONE® LISPRO

BIOCHAPERONE® LISPRO: a more physiological ultra rapid insulin

The benefits of accelerating insulin

lispro

Prandial insulins are used to regulate glycemia after a meal. In a healthy individual, meal consumption immediately triggers insulin secretion to metabolize carbohydrates.

This secretion decreases when the blood glucose level goes down again. Consequently, in order to match this action profile, injected prandial insulins must act very rapidly and for only a few hours. This has led to prandial insulin treatment evolving towards faster-acting insulins.
Insulin analogs currently on the market need to be injected 5 to 15 minutes before a meal (vs. 30 minutes for older treatments such as recombinant human insulin).

For practical reasons, patients would benefit from dosing their insulin at the time of the meal, or after the meal. This would also allow them to inject a more accurate dose relative to the meal, where the exact contents are usually better known when the meal actually starts.

Ultra-rapid insulins aim to mimic how the pancreas physiologically delivers insulin: at the time of the meal, and in proportion to its glycemic value.

 

An ULTRA-RAPID INSULIN: for WHOM?

 

 160729 Photos Lispro revues suite demande NOVO

 

The development of a range of ultra-rapid insulin, while useful to improve glycemic control in all insulin users, is especially important for specific populations of patients with diabetes:

–        Children:  it is especially challenging to know when a child will actually eat, and how much. To avoid the risk of severe hypoglycemia, parents tend to inject their diabetic child with insulin at the time of the meal or after the meal, which, with current commercialized prandial insulins, may result in hyperglycemia. In the long run, chronic hyperglycemia is correlated with serious diabetes complications. An ultra-rapid insulin should allow to inject the right dose, at the right time.

–        Insulin pump users: delivering an ultra-rapid insulin is critical to facilitate the development of efficient, fully automated insulin pumps (so-called “artificial pancreas”) that would allow automatic insulin delivery depending on the patient’s glucose level, at all times. By enhancing the system’s reactivity, faster insulins should allow it to increase the time patients spend in the right glycemic range. For current pump users, the development of a concentrated ultra-rapid insulin may also facilitate the miniaturization of devices and/or enhanced autonomy between two fills.

–        Highly insulin-resistant T2D patients:  for these patients, a concentrated ultra-rapid insulin would improve glycemic control while limiting the volume and number of injections per day.

 

BioCHAPERONE LISPRO U100: AN ULTRA-RAPID INSULIN IN ADVANCED CLINICAL DEVELOPMENT

To date, BioChaperone Lispro U100 has been successfully tested in four clinical studies (including the pilot bioequivalent study vs. BioChaperone Lispro U200).

 

BC LISPRO U100 – RECENT CLINICAL RESULTS

Effect of BioChaperone Lispro on glycemic control after a meal in patients with type 1 diabètes.

In June 2015, Eli Lilly and Adocia announced topline positive results from the first meal study of BioChaperone Lispro U100, showing that BioChaperone Lispro injected at the time of the meal was associated with a 61 percent reduction in post-prandial glucose excursion over the first two hours compared to Humalog.

The detailed results from this study were submitted for presentation at the 2016 ADA Scientific sessions and thus will remain under embargo until June 9th 2016 (conference date).

 

Effect of repeated administration of BioChaperone Lispro on glycemic control after a meal in patients with type 1 diabètes.

In March 2016, Lilly and Adocia jointly announced positive topline results of a study evaluating the effect of repeated administration of BioChaperone Lispro on glycemic control after a meal (three administrations a day, for 14 days). At the beginning of each 14-day treatment period, BioChaperone Lispro U100 demonstrated a statistically significant decrease of 31% of the glycemic excursion during the first two hours, compared to Humalog®, when treatments were injected at the time of a standardized solid meal.  At the end of the 14-day treatment period, that difference reached 42%.

The robust performance of BioChaperone Lispro after two weeks, in close-to-real-life conditions of use, is one of the key take-away messages of this study. It also showed a very good tolerability profile for BioChaperone Lispro after outpatient repeated administration.

The effect of the time of injection (15 minutes before, 15 minutes after or at the time of the meal) was also measured, but these results remain confidential.

 

Effect of repeated administration of BioChaperone Lispro on controlling blood glucose levels after meals in people with type 2 diabetes (3 administrations per day, for 14 days).

In April 2016, Eli Lilly and Adocia announced during 14-day period of treatment in people with type 2 diabetes, BioChaperone Lispro U100 showed a statistically significant 22% reduction in blood glucose excursions during the first two hours compared to Humalog when the treatments were injected at the time of a standardized solid meal.

To see the Press Release

 

Effect of administering BioChaperone Lispro U100 in people with type 1 diabetes using an insulin pump

In December 2016, Adocia and Eli Lilly reported having confirmed the effect of BioChaperone Lispro on postprandial blood glucose levels in people with type 1 diabetes using an insulin pump. During this study, BioChaperone Lispro U100 demonstrated a statistically significant increase in insulin exposure over the first 30 minutes after a mealtime bolus compared to Humalog. The accelerated absorption profile of BioChaperone Lispro U100 was also observed in the three insulin delivery devices tested (Roche AccuChek® Spirit, Medtronic Paradigm® Veo™ and insulin syringe).

To see the Press Release

 

In June 2017, Adocia initiates a study comparing ultra-rapid insulin BioChaperone® Lispro U100 with Fiasp® and Novolog® administered with an insulin pump.

The study aims to compare the pharmacokinetic and pharmacodynamic profiles of BioChaperone Lispro U100 to those of Fiasp and Novolog in participants with type 1 diabetes under a euglycemic clamp procedure.

The purpose of the study includes the comparison of the glucose response obtained during the first hour after administration of BioChaperone Lispro U100 to those obtained after administration of Fiasp and Novolog and the evaluation of the pharmacokinetic profiles of BioChaperone Lispro U100, Fiasp and Novolog. A futher objective is to assess the safety and tolerability of the three treatments in these participants.

Topline results are expected by year end.

To see the Press Release

 

BC LISPRO U100 – Previous results

The results from the meal study (above) correlate well with previous results from studies performed by Adocia:

  • The first, fundamental study evaluated the pharmacokinetic and pharmacodynamics profiles of BioChaperone® Lispro versus Humalog®. The pharmacokinetic chart below demonstrates that BioChaperone® Lispro is significantly faster than Humalog® with both a faster-in and faster-out profile.

insulin

These clinical results were presented at two major diabetes congresses in 2014 (ADA & EASD)

 

  • In a second study completed by Adocia in September 2014, BioChaperone Lispro U100 also demonstrated a linear pharmacokinetic profile across a standard therapeutic dose range.

 

160301 Graphe BC Lispro 0.4 Ukg 2016 ENG VF

 

Results of this study were presented at the scientific session of ADA 2015

 

BC LISPRO U100 – ongoing clinical results

There are currently four ongoing clinical studies evaluating BioChaperone Lispro U100:

Results for these studies are expected in 2016. Further clinical development plans for BioChaperone Lispro remain confidential.

BioChaperone Lispro U200: a unique concentrated ultra-rapid prandial insulin

BioChaperone Lispro U200 may become the first concentrated ultra-rapid prandial insulin. No such product is currently on the market.

A concentrated ultra-rapid prandial insulin may meet the needs of two main populations of insulin users:

  • Highly insulin resistant patients: for patients who need a higher daily dose of insulin, increasing the concentration allows to decrease the volume to be injected and the number of injections per day.
  • Patients using insulin pumps (estimated to represent 46% of type 1 diabetes patients in the US): for these patients, concentrated insulin may enable smaller; more easily wearable pumps or pumps that last longer, limiting the need for refills. This could greatly contribute to their day-to-day quality of life.

Humalog U200 (Eli Lilly), a twice as concentrated formulation of Humalog, was recently approved in the USA and in Europe. It is currently the only concentrated prandial insulin analog on the market.

 

Feasibility study testing the potential bioequivalence of BioChaperone Lispro U200 with BioChaperone Lispro U100

In December 2015, Adocia and Eli Lilly jointly announced positive results for a pilot bioequivalence feasibility study, which triggered a $10M milestone payment from Lilly.

 

The study aimed to test the potential bioequivalence of BioChaperone Lispro U200 and U100 formulations. The results showed that BioChaperone Lispro U200 met all predefined endpoints and retained the ultra-rapid profile of BioChaperone U100. Consequently, BioChaperone Lispro U200 could be developed as a bioequivalent product to BioChaperone Lispro U100; in this case, only one additional pivotal bioequivalence study would be needed to submit the product for approval, based on the dossier for BioChaperone Lispro U100.

The detailed results from this study were submitted for presentation at the 2016 ADA Scientific sessions and thus will remain under embargo until June 9th 2016 (conference date).

 

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