Sanofi Presented Full Results of a PK/PD Study Comparing Toujeo（R） to Insulin Degludec in People With Type 1 Diabetes

PR66500

PARIS, November 12, 2016 /PRNewswire=KYODO JBN/ --

      - Toujeo(R) provides a flatter profile than insulin degludec with less

within-day fluctuations -

    Sanofi [http://www.sanofi.com ] presented today the full results of a

pharmacokinetic / pharmacodynamic (PK/PD) study with Toujeo(R) (insulin

glargine 300 Units/mL) and insulin degludec 100 Units/mL (Deg-100) at the 16th

Annual Diabetes Technology Meeting, Bethesda, Maryland, U.S.[1]

    In patients with type 1 diabetes, the Toujeo(R) PK/PD profile at a

clinically relevant dose (0.4 U/kg/day, the average dose used in worldwide

clinical practice)[2] was flatter and more evenly distributed over 24 hours

compared with the profile of insulin degludec. The within-day fluctuation of

metabolic activity was 20% lower (p=0.047) for Toujeo(R) than insulin degludec.

    An overall flat PK/PD profile and an evenly distributed exposure over 24

hours were observed for Toujeo(R) at both dose levels studied (0.4 and 0.6

U/kg/day).

    "These new findings may have clinical implications for people with type 1

diabetes on basal insulin therapy," said Dr. Timothy Bailey, Clinical Associate

Professor, University of California, San Diego. "Toujeo(R) has already shown an

improved PK/PD profile when compared to insulin glargine 100 Units/mL

(Gla-100), with a flatter profile. Also in a previous CGM study[3] in adults

with type 1 diabetes versus Gla-100, Toujeo showed less between-day variability

and less within-day fluctuations, associated with a lower risk of nocturnal

confirmed (less than or equal to54 mg/dL) or severe hypoglycemia in the first 8

weeks.[3] The results observed in the current PK/PD study comparing Toujeo(R)

versus Deg-100 confirm that Toujeo has an interesting profile with the

potential to help the people with diabetes to reach their targets with less

risk of hypoglycemia."

    "In this PK/PD study, we observed a more favorable profile for Toujeo(R)

compared to insulin degludec," said Riccardo Perfetti, Head of Global Diabetes

Medical Team, Sanofi. "The clinical implications of these findings are

currently being investigated."

    About Toujeo(R) PK/PD study (LPS14585)[1]

    Rationale:

    Although basal insulin injections cannot perfectly replicate endogenous

insulin production, the 'ideal' basal insulin for diabetes therapy would have

stable pharmacodynamic (PD) and pharmacokinetic (PK) profiles. Smaller and less

variable glucose excursions may result in more predictable 24hour profiles and

less hypoglycemia, and could translate into an improved experience for people

on basal insulin and better adherence to therapy.

    Study design:

    This was a randomized, double-blind, 2x2, crossover, euglycemic-clamp study

in two parallel cohorts of people with type 1 diabetes (48 people in total) to

compare the pharmacodynamic and pharmacokinetic properties of 0.4 and 0.6

U/kg/day insulin glargine 300 Units/mL (Toujeo(R), Gla-300) with the same dose

levels of insulin degludec 100 Units/mL (Deg-100) in steady state after 8 days

multiple dosing regimen.

    Key results:

    Pharmacodynamics:

    Within-day fluctuation of the smoothed glucose infusion rate (GIR-smFL0-24)

was significantly lower with Gla-300 versus Deg-100 at the 0.4 U/kg dose level.

At the 0.4 U/kg dose level, relative 6-hour fractions of GIR-AUC0-24 were more

evenly distributed with Gla-300 versus Deg-100. GIR-smFL0-24 and 6-hour

fractions of GIR-AUC0-24 were similar between insulins at the supra-therapeutic

0.6 U/kg dose level. At both dose levels, GIR-AUC0-24 and GIRmax were lower for

Gla-300 versus Deg-100, while T50%-GIR-AUC0-24 and duration of BG control were

similar foreach insulin.

    Pharmacokinetics:

    Both dose levels of Gla-300 provided plateau-like insulin profiles up to 16

hours post-dose, followed by a subsequent slow decline. For Deg-100, insulin

increased at both dose levels from the time of injection until ~10 hours after

dosing, with subsequent slow decline. Exposure of both insulins was measurable

until clamp end (30 hours). At both dose levels the 6-hour fractions of

INS-AUC0-24 were more evenly distributed with Gla-300 versus Deg-100.

    About Toujeo(R) CGM study[3]

    Rationale:

    Continuous glucose monitoring (CGM), is a valuable way to confirm whether

the differences observed in the PK and PD properties of insulins under

experimental condition translate to clinically relevant differences in their

24-hour glucose profiles and other parameters of glycemic control, including

hypoglycemia.

    Study design:

    This was a multicenter, 16-week, open-label, Phase II, parallel-group,

two-period crossover study including 59 people with type 1 diabetes (PDY12777;

NCT01658579). The primary endpoint was the mean percentage of time within the

glucose range of 4.4-7.8 mmol/L (80-140 mg/dL) during the last 2 weeks of

treatment in each treatment period (Weeks 7-8 and Weeks 15-16). The main

secondary endpoints were the average 24-hour glucose profiles based on CGM

(mmol/L) for the last 2 weeks of treatment in each treatment period and the

incidence of participants experiencing at least one hypoglycemic event (defined

by American Diabetes Association criteria) in either study period.

    Key results:

    The percentage of time within the glucose range of 4.4-7.8 mmol/L (primary

endpoint) was similar for participants receiving Gla-300 vs Gla-100 (LS mean

difference 0.75%, p=0.73). Average 24-hour glucose profiles showed a more

constant glucose level with Gla-300 vs. Gla-100.

    About Toujeo(R)

    Toujeo(R) is a once-daily basal insulin based on a broadly-used molecule

(insulin glargine). Toujeo has been approved by the U.S. Food and Drug

Administration (FDA), the European Commission, Health Canada, the Therapeutic

Goods Administration in Australia, and the MHLW in Japan (where its approved

brand name is Lantus(R) XR), and is under review by other regulatory

authorities around the world.

    About Sanofi

    Sanofi, a global healthcare leader, discovers, develops and distributes

therapeutic solutions focused on patients' needs. Sanofi is organized into five

global business units: Diabetes and Cardiovascular, General Medicines and

Emerging Markets, Sanofi Genzyme, Sanofi Pasteur and Merial.

    References:

    1) Bailey T, et al. Insulin Glargine 300 U/mL (Gla-300) Provides More

Stable and More Evenly Distributed Steady-state PK/PD Profiles Compared with

Insulin Degludec in Type 1 Diabetes. Poster presented at Diabetes Technology

Meeting, November 11, 2016

    2) Data on file, Adelphi Real World Diabetes DSP XII, 2015.

    3) Bergenstal RM, et al. Diabetes Technol Ther 2015;17(S1):16 (Abstract 39)

    Source: Sanofi