- In Phase Ia clinical study, GZR4 demonstrated favorable
safety and tolerability profiles in healthy subjects, maintaining a
stable glucose-lowering effect for up to one week with a single
administration.
- In Phase Ib clinical study, patients with Type 2 diabetes
mellitus (T2DM) receiving six weeks of GZR4 treatment were safe and
well tolerated. GZR4 also exhibited improvements in fasting blood
glucose (FBG), glycated hemoglobin (HbA1c), and time in range (TIR)
across all dosage groups, outperforming the insulin degludec (IDeg)
group.
BEIJING, Sept. 14, 2024 /PRNewswire/ -- Gan & Lee
Pharmaceuticals (Gan & Lee, Shanghai Stock Exchange: 603087)
announced the clinical results from two Phase I trials of the
Company's independently developed novel once-weekly insulin analog,
GZR4, in healthy Chinese subjects and patients with T2DM in oral
presentation and short oral discussion at the 60th Annual Meeting
of the European Association for the Study of Diabetes (EASD
2024).
Statement:
1. GZR18
injection is an investigational drug and has not yet been approved
in China.
2.
Gan & Lee Pharmaceuticals does not recommend the use of any
unapproved drugs/indications.
Phase Ia Study Results
This placebo-controlled and active-comparator-controlled,
single-center, single-dose, randomized, dose-escalation study
aimed to evaluate the safety, tolerability, pharmacokinetics (PK),
and pharmacodynamics (PD) of GZR4 in healthy adult male
participants. The study was conducted following a dose-escalation
design, starting from lower doses and progressively increasing to
higher doses. Participants in cohorts 1-4 randomly receiving a
subcutaneous injection of GZR4 (1, 3, 6, or 12 nmol/kg) or placebo,
while cohort 5 received a single dose of 0.4 U/kg (2.4 nmol/kg)
insulin degludec (IDeg) as an active comparator. A 24-hour glucose
clamp procedure was conducted on days 2 and 7 respectively
post-GZR4 administration in cohorts 2-4, and on day 1 post-IDeg
administration in cohort 5.
GZR4 exhibited favorable safety and tolerability in healthy
subjects, with no serious adverse events (SAEs) reported, and no
discontinuations due to the investigational product-related adverse
events. PD results indicated that the glucose infusion rate (GIR)
on day 7 was approximately 80% of that on day 2 in subjects
receiving 12 nmol/kg GZR4, indicating that the
glucose-lowering effect of GZR4 persists for approximately one
week. Meanwhile, the area under the GIR-time curve on day 2
(AUCGIR,24-48h) and day 7 (AUCGIR,144-168h)
for the 6 nmol/kg dose of GZR4 was similar to the 24-hour GIR
(AUCGIR,0-24h) for the 0.4 U/kg (2.4 nmol/kg) of IDeg
(37.84 ± 9.86 versus 40.60 ± 14.39 h*mg/kg/min,
respectively)*, implying that the average daily
glucose-lowering effect of GZR4 is comparable to that of IDeg.
Convert accordingly, it is estimated that the potency of GZR4 is
approximately 2.5-fold greater than that of IDeg when evaluating
based on a similar molar concentration.
Phase Ib Study Results
In this randomized, open-label, active-controlled, multi-center,
dose-escalation Phase Ib trial, a total of 36 patients with T2DM
who had previously been treated with basal insulin were randomized
in a 3:1 ratio to receive a fixed once-weekly dose of GZR4 (6, 8,
or 12 nmol/kg) or once-daily (IDeg) (equal to the pre-enrolment
daily basal insulin dosage) for 6 weeks.
PK results showed that the maximum plasma concentration
(Cmax) of GZR4 increased dose-dependently, while the
time to maximum concentration (Tmax) and half-life were
approximately 32 hours and 135 hours at steady state, respectively.
PD data indicated dose-dependent reductions in FBG (-1.77 ± 0.20,
-2.03 ± 0.66, and -2.75 ± 0.71 mmol/L for GZR4 in 6, 8, and 12
nmol/kg groups, respectively) in week 6, which outperformed
the IDeg group (-1.12 ± 0.36 mmol/L*). After 6 weeks of
treatment, the 6 nmol/kg GZR4 group demonstrated a reduction in
HbA1c of 0.76 ± 0.14%, compared to the reduction of 0.13 ± 0.21% *
in the IDeg group.
In patients with T2DM, GZR4 demonstrated good safety and
tolerability. No serious adverse events were reported in all
treatment groups; the most frequently reported treatment-emergent
adverse event was hypoglycaemia, but no severe hypoglycemia
occurred.
The detailed results of the Phase I studies will be published in
a peer-reviewed journal.
*Trial data are presented as mean ± standard error.
Gan & Lee Pharmaceuticals also announced
announced that a multicenter, randomized, open-label, parallel-control, treat-to-target phase 2
study is underway in patients with T2DM who have inadequate
glycemic control with oral antidiabetic drugs, including
insulin-naïve patients and patients on basal insulin. The study
enrolled 179 adult participants and compares the efficacy and
safety of once-weekly GZR4 with once-daily insulin degludec. All
participants have completed treatment, and preliminary results are
promising, further validating the findings from the Phase I
studies.
Dr. Gan Zhong-ru, Chairman of Gan & Lee Pharmaceuticals,
commented: "A significant number of patients with Type 2 diabetes
mellitus are experiencing delays in initiating
insulin therapy and exhibit poor long-term adherence to
treatment,etc. The introduction of weekly insulin preparations has
the potential to significantly improve the aforementioned
challenges. The completed Phase I trials confirmed GZR4's ability
to provide stable glycemic control for a full week with a single
dose, along with favorable safety and tolerability profiles.
In addition, GZR4 is expected to reduce the weekly dosage of
insulin required reaching the glycemic target, thereby reducing the
possible risk of hypoglycaemia. We look forward to continuing to
explore the clinical benefits of GZR4 in future trials."
About Gan & Lee
Gan & Lee Pharmaceuticals developed the first Chinese
domestic insulin analog. Currently, Gan & Lee has six core
insulin products, including five insulin analog varieties:
long-acting glargine injection (Basalin®), fast-acting
lispro injection (Prandilin™), fast-acting aspart
injection (Rapilin®), mixed protamine zinc lispro
injection (25R) (Prandilin™25), aspart 30 injection
(Rapilin®30), and one human insulin injection - mixed
protamine human insulin injection (30R)
(Similin®30). The company has two approved
medical devices in China,
namely reusable insulin injection
pen (GanleePen), and disposable pen needle
(GanleeFine®).
In China's 2024 National
Insulin-Specific Centralized Procurement, Gan & Lee
Pharmaceuticals ranked second overall and first among domestic
companies in terms of procurement demand for insulin analogs. The
company is also making strides in international markets, with the
disposable pen needle (GanleeFine®) approved by the US
Food and Drug Administration (FDA) in 2020 and received GMP
inspection approval from the European Medicines Agency (EMA) in
2024. These achievements significantly boost Gan & Lee's
competitiveness in both international and domestic markets.
In the future, Gan & Lee will strive for comprehensive
coverage in diabetes treatment. Moving forward with its mission to
become a world-class pharmaceutical company, Gan & Lee will
also actively develop new chemical entities and biological drugs,
focusing on treatments for metabolic diseases, cardiovascular
diseases, and other therapeutic areas.
Forward-looking statements
Forward-looking statements are based on our expectations and
assumptions as of the date of the statements. Actual results may
differ materially from those expressed in these forward-looking
statements due to a variety of factors, and we can give no
assurance that such results will be achieved in the future. We
undertake no obligation to update or revise any forward-looking
statements, whether as a result of new information, future events,
or otherwise.
Further Information:
BPRD@ganlee.com (Media)
BD@ganlee.com (Business Development)
info.medical@ganlee.com (Medical Information)
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