Innovent announces the results of the Phase III clinical study (CREDIT-1) of tolesimab (IBI306) in patients with non-familial hypercholesterolemia at the 2022 American Heart Association Annual Meeting (AHA 2022).

Innovent Biopharmaceutical Group (HKEx stock code: 01801), a biopharmaceutical company dedicated to the development, production and sales of innovative drugs for the treatment of major diseases such as oncology, autoimmunity, metabolism, ophthalmology, etc.
, announced: Innovent Biologics independently developed anti-proprotein converting enzyme subtilisin 9 (PCSK-9) monoclonal antibody (toleximab, R&D code: IBI306) The results of the Phase III clinical study (study code: CREDIT-1) in patients with non-familial hypercholesterolemia in China were accepted as conference abstracts and published
in poster form (number: VP173) at the 2022 American Heart Association Annual Meeting (AHA 2022).

Cardiovascular disease is currently the leading cause of death in China, and hypercholesterolemia is one of the
most important risk factors for cardiovascular disease.
Chinese guidelines for the prevention and treatment of dyslipidemia in adults recommend statin therapy as the cornerstone of lipid control, but for many reasons, most patients with hypercholesterolemia, especially those with high-risk and very high-risk cardiovascular risk factors, still cannot achieve the target value of low-density lipoprotein cholesterol (LDL-C) under the treatment of statins, and often need to start combination therapy
with non-statins.
In recent years, PCSK9 inhibitors have demonstrated significant lipid-lowering effects, providing new treatment options
for these patients.
Toleximab is an innovative biological drug independently developed by Innovent and the first PCSK-9 monoclonal antibody
to carry out long-term, large-scale, randomized double-blind phase III clinical research in China.

The findings are based on a randomized, double-blind, placebo-controlled phase III clinical study (ClinicalTrials.
gov, NCT04289285) to evaluate the efficacy and safety
of toleximab in Chinese subjects with non-familial hypercholesterolemia 。 Patients with nonfamilial hypercholesterolemia who received stable lipid-lowering therapy for at least 4 weeks were randomized 2:2:1:1 to receive toleximab 450 mg Q4W, toleximab 600 mg Q6W, placebo 450 mg Q4W, and placebo 600 mg Q6W during a 48-week double-blind treatment period
.
The primary endpoint of the study was the percentage change
in LDL-C level from baseline at week 48.

A total of 618 patients (baseline LDL-C level: 2.
85 mmol/L) were included in the study, and 614 participants received at least one dose
.
The results showed that toleximab 450 mg Q4W and 600 mg Q6W were effective in reducing LDL-C levels
compared with placebo at week 48.

● At week 48, the between-group difference in LDL-C level change from baseline percentage was −65.
0% (P<0.
0001) in the toleximab 450 mg Q4W group and −57.
3% (P<0.
0001) in the toleximab 600 mg Q6W group compared with placebo
.

● In the toleximab 450 mg Q4W group, 87.
8% of subjects had LDL-C levels reduced by more than 50%; LDL-C <1.
8 mmol/L in 91.
7% of participants; 83.
4% of participants had LDL-C <1.
4 mmol/L
.

● In the toleximab 600 mg Q4W group, 71.
8% of subjects had LDL-C levels reduced by more than 50%; LDL-C <1.
8 mmol/L in 82.
1% of participants; LDL-C <1.
4 mmol/L
in 68.
7% of participants.

At the same time, the two dosing regimens of toleximab also significantly reduced non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), and lipoprotein a (Lp(a))
compared with placebo.
During the study, the overall safety profile of tolesimab was close
to that of similar products already on the market.

The results of these studies suggest that subcutaneous administration of toleximab 450 mg Q4W and 600 mg Q6W can significantly and durably reduce LDL-C levels and demonstrate a good safety profile
.
In June 2022, the new drug marketing authorization application (NDA) for toleximab injection was accepted by the National Medical Products Administration (NMPA) for the treatment of primary hypercholesterolemia (including heterozygous familial and non-familial hypercholesterolemia) and mixed dyslipidemia, which is expected to become the first PCSK-9 monoclonal antibody drug
approved for marketing in China.

Professor Huo Yong, principal investigator of the CREDIT-1 study, Peking University First People's Hospital, said: "CREDIT-1 is a large-scale clinical trial to verify the efficacy and safety of PCSK9 inhibitors in Chinese patients with non-familial hypercholesterolemia, and we are pleased to present the results of this exciting clinical study
at this year's AHA Conference 。 The study found that under the long dosing interval (4 weeks or 6 weeks), toleximab can significantly reduce LDL-C levels, and also have a significant effect on other blood lipid indicators, and the overall data show that the treatment of tolecymab in Chinese patients with non-familial hypercholesterolemia has obvious benefits and good safety
.
I am very confident in the clinical application of tolecymab and look forward to its approval next year, bringing a curative, safe and reliable treatment plan to Chinese patients with hypercholesterolemia
.
" "

Dr.
Qian Lei, Clinical Vice President of Innovent Biopharmaceutical Group, said, "In the CREDIT-1 study, toleximab demonstrated significant efficacy and good safety
in Chinese patients with non-familial hypercholesterolemia.
Tolecyximab is the pioneer of PCSK9 inhibitors independently innovated in China, and the CREDIT-1 study, as the first registered clinical study of PCSK9 inhibitors to appear on the international academic stage, shows the excellent scientific research level of Chinese researchers and the solid research and development capabilities
of Innovent Company.
The new drug application for tolesimab has been officially accepted by CDE, and we expect that China's first local PCSK9 innovative drug will be approved early next year to serve the majority of patients
with cardiovascular disease and hyperlipidemia.
"

On hypercholesterolemia

In recent years, the blood lipid level of Chinese group has gradually increased, and the prevalence of dyslipidemia has increased
significantly.
The overall prevalence of dyslipidemia in Chinese adults is as high as 40.
4
%.
The increase in serum cholesterol levels in the population will lead to an increase of about 9.
2 million cardiovascular disease events in China during 2010~2030.

At present, the treatment of hyperlipidemia in China is not optimistic
.
According to the 2020 China Cardiovascular Health and Disease Report, the awareness rate, treatment rate and control rate of dyslipidemia in adults in China are still at a low level
at this stage.
Anti-PCSK-9 monoclonal antibody can effectively reduce LDL-C levels, which is expected to provide a better treatment option
for Chinese patients with hypercholesterolemia.

About IBI306 (PCSK-9 inhibitor)

IBI306 is an innovative biological drug independently developed by Innovent Biologics, IgG2 monoclonal antibody, which can specifically bind to PCSK-9 molecules, increase LDLR levels by reducing PCSK-9-mediated low-density lipoprotein receptor (LDLR) endocytosis, thereby increasing LDL-C clearance and reducing LDL-C levels
.

To date, three registered clinical studies of tolesimab, CREDIT-2, CREDIT-1 and CREDIT-4, have been completed
.
The results of the phase I/II clinical study were published in JACC Asia
, an internationally renowned cardiology journal JACC.
The results of the CREDIT-2 clinical study were accepted by the 2022 American College of Cardiology Annual Meeting (ACC 2022) and presented
in the conference poster.
The results of CREDIT-1's clinical studies were also accepted and presented
in the form of a conference poster at the 2022 American Heart Association Annual Scientific Meeting (AHA 2022).

Three key registrational clinical studies on IBI306

The CREDIT-1 study is a randomized, double-blind, placebo-controlled phase III clinical study (ClinicalTrials.
gov, NCT04289285)
to evaluate the efficacy and safety of toleximab in Chinese patients with non-familial hypercholesterolemia (hypercholesterolemia combined with high-risk/very high-risk cardiovascular risk).
The primary clinical endpoint was LDL-C reduction from baseline at 48 weeks of treatment
.
The results of the study were presented
in poster format at the 2022 AHA Annual Meeting.

The CREDIT-2 study is a randomized, double-blind, placebo-controlled phase III clinical study (ClinicalTrials.
gov, NCT04179669) to evaluate the efficacy and safety of tolecymab in subjects with heterozygous familial hypercholesterolemia in China
.
The primary efficacy endpoint was the percentage reduction of LDL-C from baseline at 12 weeks of treatment
.
Some of the results of the study were published
in poster format at the 2022 ACC Annual Meeting.

The CREDIT-4 study is a randomized, double-blind, placebo-controlled phase III clinical study (ClinicalTrials.
gov, NCT04709536) to evaluate the efficacy and safety of toleximab in patients with hypercholesterolemia (including non-familial hypercholesterolemia and heterozygous familial hypercholesterolemia) in China
.
The primary clinical endpoint was 12 weeks of treatment with LDL-C as a percentage reduction from baseline
.