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

Paris (ots/PRNewswire) -

- Toujeo® 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®
(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® 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® than insulin degludec.

An overall flat PK/PD profile and an evenly distributed exposure
over 24 hours were observed for Toujeo® 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® 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 (<=54 mg/dL) or severe hypoglycemia in the first 8
weeks.[3] The results observed in the current PK/PD study comparing
Toujeo® 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® 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® 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®, 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® 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®

Toujeo® 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® 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)

ots Originaltext: sanofi-aventis Group
Im Internet recherchierbar: http://www.presseportal.de

Contact:
Global Diabetes Communications
Serge Spierckel
+33(0)6-75-71-61-24
serge.spierckel@sanofi.com

Investor Relations
George Grofik
+33(0)1-53-77-45-45
ir@sanofi.com

Corporate Communications
Mai Tran
+33(0)1-53-77-49-86
mai.tran@sanofi.com

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