Innovent Releases Results of a Phase 3 Clinical Study of IBI306 (PCSK-9 inhibitor) in Chinese Patients with Heterozygous Familial Hypercholesterolemia at the American College of Cardiology Annual ...

SAN FRANCISCO and SUZHOU, China, April 3, 2022 /PRNewswire/ -- Innovent Biologics, Inc. (Innovent) (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of oncology, metabolic, autoimmune and other major diseases, announces that the results of a phase 3 clinical trial (Study code: CREDIT-2) of recombinant full-human anti-PCSK-9 monoclonal antibody (R&D code: IBI306, independently developed by Innovent) in Chinese patients with heterozygous familial hypercholesterolemia (HeFH) have been accepted as an abstract presented (E-poster #: 1188-005) at the American College of Cardiology Annual Congress 2022 (ACC 2022).

PCSK-9 inhibitors, which can potently reduce LDL-C levels with a good safety profile, have been gradually recognized by clinicians as novel therapeutic regimens in recent years. Although there are various imported PCSK-9 inhibitors marketed in the Chinese market, there are some limitations in terms of economy and convenience. IBI306 is an innovative drug independently developed by Innovent. It is the PCSK-9 inhibitor that take the lead in carrying out long-term, large-scale, randomized and double-blind phase III clinical studies in China (CREDIT-1, CREDIT-2 and CREDIT-4), and explored and optimized the treatment regimen with long-interval dosing.

The AAC 2022 presentation is based on CREDIT-2, a randomized, double-blind, placebo-controlled phase 3 study, evaluating the efficacy and safety of IBI306 in Chinese patients with heterozygous familial hypercholesterolemia (ClinicalTrials.gov, NCT04179669). During the 12-week double-blind treatment period, patients previously received a stable lipid-lowering therapy for at least 4 weeks were randomized 2:1:2:1 to receive subcutaneous injection of IBI306 or placebo 150 mg Q2W, or IBI306 or placebo 450 mg Q4W respectively. In week 12-24, patients in control groups continued to receive IBI306 with the previous regimens; while patients in placebo groups were crossed over to receive open-label IBI306 150 mg Q2W or 450 mg Q4W, respectively. The primary endpoint was the percent change in LDL-C levels from baseline to week 12.

The results of study showed that both IBI306 150 mg Q2W or 450 mg Q4W yielded significant reduction in LDL-C levels in Chinese patients with HeFH. As for the Primary endpoint: IBI306 significantly reduced LDL-C levels (treatment difference versus placebo: −57.4% [97.5% CI, −69.2% to −45.5%] for 150 mg Q2W; −61.9% [−73.4% to −50.4%] for 450 mg Q4W; P<0·0001 for both comparisons). And for the key secondary endpoint: significantly more patients treated with IBI306 achieved ≥50% LDL-C reductions at week 12 as compared with corresponding placebo groups (58.5% [97.5% CI, 42.2% to 74.8%] for 150 mg Q2W; 73.4% [58.5% to 88.4%] for 450 mg Q4W; P<0·0001 for both comparisons). IBI306 significantly reduced Lp(a) levels (treatment difference versus placebo: -43.3% [95% CI, −58.9% to -27.6%] for 150 mg Q2W; −34.1% [−47.1% to −21.1%] for 450 mg Q4W; P<0·0001 for both comparisons). In addition, IBI306 treatment induced various improvements including LDL-C < 1.8 mmol/L response rate, non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB) and other Lipid parameters after 12 weeks of treatment. At the same time, the LDL-C reduction in the IBI306 groups was well maintained at 50% and above throughout 24 weeks. The overall safety profile of IBI306 in the study was favorable and similar to the safety profile of other marketed PCSK-9 inhibitors.

Prof. Yujie Zhou, principal investigator of CREDIT-2 study and Vice President of Anzhen Hospital, from the Capital Medical University, stated, "CREDIT-2 is the first large-scale phase 3 trial in China to demonstrate the efficacy and safety of PCSK-9 inhibitors in Chinese patients with HeFH. As a domestic innovative PCSK-9 inhibitor, IBI306 can significantly reduce LDL-C levels and improve other lipid parameters to certain extent. The overall data showed that IBI306 had significant therapeutic benefits and favorable safety in Chinese patients with HeFH. I am confident that it will be an alternative and accessible treatment option for Chinese patients with HeFH."

Dr. Lei Qian, Vice President of Innovent, stated: " In CREDIT-2, IBI306 showed significant efficacy and good safety in Chinese patients with HeFH. As pioneering the development progress of PCSK-9 inhibitors in China, CREDIT-2 showed the excellent scientific research capabilities of Chinese researchers, as well as the solid and strong execution in R&D of Innovent Biologics. At the same time, the results of other registrational studies of IBI306 will also be disclosed in this year and next year, bringing more high-quality evidence-based clinical study result based in China to the global medical research community. We plan to submit a new drug application for IBI306 this year and actively communicate with regulatory authorities, hoping to benefit the majority of patients in China with more high-quality biological drugs as soon as possible."

About Hypercholesterolemia

In recent years, the blood lipid level of the Chinese population has gradually increased, and the prevalence of dyslipidemia has increased significantly with an overall prevalence of 40.4% in Chinese adults. The increase of serum cholesterol level in the population will lead to an increase of about 9.2 million cardiovascular disease events in China during 2010 ~ 2030. Familial hypercholesterolemia (FH) is an autosomal dominant disorder characterized by markedly elevated serum LDL-C levels. The vast majority of FH patients are due to single allele mutations and are classified as HeFH. The incidence of HeFH is about 1 / 500 to 1 / 200.

At present, the management of hyperlipidemia in China is not optimistic. According to the 2020 China Cardiovascular Health and Disease Report, the diagnostic, treatment and control rate of dyslipidemia in Chinese adults remain low. The percentage of patients with dyslipidemia who met the LDL-C reduction goal is even more alarming. Current lipid-lowering therapies do not meet the clinical needs in patients with hyperlipidemia. Anti-PCSK-9 monoclonal antibody has a mechanism of action different from existing lipid-lowering drugs and 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, developed by Innovent, is an lgG2 fully human monoclonal antibody that can specifically bind to PCSK-9 and reduce LDL-C level by inhibiting PCSK-9-mediated low-density lipoprotein receptor (LDLR) endocytosis, subsequently enhancing the clearance of LDL-C, resulting in a reduction in LDL-C level.

As of now, three IBI306 registration trials have met the primary endpoint. The results from phase 1 and 2 clinical studies have been published in JACC Asia, an internationally renowned journal of cardiology. Results from the first completed CREDIT-2 phase 3 study have also been accepted and presented as a poster at the American Cardiology Association Annual Congress 2022 (ACC 2022).

About Three Registration Clinical Studies of IBI306

The CREDIT-1 study is a randomized, double-blind, placebo-controlled phase 3 clinical study to assess the efficacy and safety of IBI306 in Chinese patients with non-familial hypercholesterolemia (hypercholesterolemia with cardiovascular risk) (ClinicalTrials.gov, NCT04289285). The primary efficacy measure was the percentage reduction from baseline in LDL-C after 48 weeks of treatment.

The CREDIT-2 study is a randomized, double-blind, placebo-controlled phase 3 study to evaluate the efficacy and safety of IBI306 in Chinese subjects with heterozygous familial hypercholesterolemia (ClinicalTrials.gov, NCT04179669). The primary efficacy endpoint was the percentage reduction from baseline in LDL-C after 12-week treatment.

The CREDIT-4 study was a randomized, double-blind, placebo-controlled phase 3 clinical study to assess the efficacy and safety of IBI306 in Chinese patients with hypercholesterolemia (including non-familial hypercholesterolemia and heterozygous familial hypercholesterolemia) (ClinicalTrials.gov, NCT04709536). The primary efficacy measure was the percentage reduction from baseline in LDL-C after 12 weeks of treatment.

About Innovent

Inspired by the spirit of "Start with Integrity, Succeed through Action," Innovent's mission is to develop, manufacture and commercialize high-quality biopharmaceutical products that are affordable to ordinary people. Established in 2011, Innovent is committed to developing, manufacturing and commercializing high-quality innovative medicines for the treatment of cancer, autoimmune, metabolic and other major diseases. On October 31, 2018, Innovent was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code: 01801.HK.

Since its inception, Innovent has developed a fully integrated multi-functional platform which includes R&D, CMC (Chemistry, Manufacturing, and Controls), clinical development and commercialization capabilities. Leveraging the platform, the company has built a robust pipeline of 29 valuable assets in the fields of cancer, metabolic, autoimmune disease and other major therapeutic areas, with 7 products – TYVYT^® (sintilimab injection), BYVASDA^® (bevacizumab biosimilar injection), SULINNO^® (adalimumab biosimilar injection), HALPRYZA^® (rituximab biosimilar injection), Pemazyre^® (pemigatinib oral inhibitor) , NAILIKE(olverembatinib) and Cyramza^® (ramucirumab), 1 asset under NMPA NDA review, 5 assets in Phase 3 or pivotal clinical trials, and an additional 19 molecules in clinical studies.

Innovent has built an international team with advanced talent in high-end biological drug development and commercialization, including many global experts. The company has also entered into strategic collaborations with Eli Lilly and Company, Adimab, Incyte, MD Anderson Cancer Center, Hanmi and other international partners. Innovent strives to work with many collaborators to help advance China's biopharmaceutical industry, improve drug availability and enhance the quality of the patients' lives. For more information, please visit: www.innoventbio.com. and www.linkedin.com/company/innovent-biologics/.

Note:

TYVYT^® (sintilimab injection) is not an approved product in the United States.

BYVASDA^® (bevacizumab biosimilar injection), SULINNO^®, and HALPRYZA^® (rituximab biosimilar injection) are not approved products in the United States.

TYVYT^® (sintilimab injection, Innovent)

BYVASDA^® (bevacizumab biosimilar injection, Innovent)

HALPRYZA^® (rituximab biosimilar injection, Innovent)

SULINNO^® (adalimumab biosimilar injection, Innovent)

Pemazyre^® (pemigatinib oral inhibitor, Incyte Corporation). Pemazyre^® was discovered by Incyte Corporation and licensed to Innovent for development and commercialization in Mainland China, Hong Kong, Macau and Taiwan.

Disclaimer:

Forward-Looking Statements 

This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words "anticipate", "believe", "estimate", "expect", "intend" and similar expressions, as they relate to Innovent, are intended to identify certain of such forward-looking statements. Innovent does not intend to update these forward-looking statements regularly.

These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections and understandings of the management of Innovent with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties and other factors, some of which are beyond Innovent's control and are difficult to predict. Consequently, actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business, Innovent's competitive environment and political, economic, legal and social conditions.

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