February 18, 2025 — AccurEdit Therapeutics (AccurEdit) releases recent clinical data from a "Multicenter, Open-Label, Single-Arm, Investigator-initiated trial (IIT) of ART002, a single-course, intravenously administered treatment for Heterozygous Familial Hypercholesterolemia". The study is sponsored by AccurEdit Therapeutics and carried out by The First Affiliated Hospital of Bengbu Medical University. The data reveals that a single dose of ART002, an in vivo gene editing product independently developed by AccurEdit Therapeutics, achieves saturation of pharmacological effect and reduces low-density lipoprotein cholesterol (LDL-C), demonstrating remarkable efficacy and outstanding safety profile. Following the suspension of early clinical trials of a similar product by U.S.-based Verve Therapeutics, ART002 has become the first in vivo gene editing product globally to achieve such a milestone in humans, representing a landmark in the treatment of hypercholesterolemia with in vivo gene editing therapy.

ART002 is a novel lipid nanoparticle (LNP)-based in vivo gene editing product designed to precisely edit the LDL-C regulatory gene PCSK9 with a single administration, enabling sustained LDL-C reduction and lowering the risk of cardiovascular disease.

Existing therapies including statins and PCSK9 antibodies, require daily intake or regular injections every few weeks. While siRNA drugs including inclisiran (administered every 6 months) improve convenience, its four-year long-term clinical studies show that even combined with high-intensity statins, the reduction of LDL-C levels is merely around 44%. Additionally, the existing medications require prolonged, periodic administration, which could lead to poorer adherence and higher costs. In contrast, with the potential to achieve long term efficacy by a single dose, ART002 is capable of reducing reliance on patient adherence, and this innovation is set to bring revolutionary changes to the precise and long-term treatment of cardiovascular diseases and other chronic conditions.

The IIT study of ART002 was carried out in mid-2024. Among the enrolled participants, more than 60% had baseline LDL-C levels exceeding 6.2 mM (240 mg/dL), significantly higher than the baseline levels in the clinical trials of inclisiran (3.3–3.7 mM) and PCSK9 antibodies (mostly 3–5 mM). The study shows that the challenge for treating participants of ART002 is greater than that for existing products.

ART002 demonstrated excellent safety profile in all participants, with no dose-limiting toxicity (DLT) events or serious adverse events observed across all dose groups.

Peak reduction of plasma PCSK9 protein was achieved 2–4 weeks post-treatment. In the medium- and high-dose groups, an average of ~90% PCSK9 knockdown was observed, with a maximum level of 93%, significantly higher than the mean reduction of 69.8% reported by the siRNA product inclisiran (ORION-10 study). Based on these results, ART002 becomes the world’s first in vivo gene editing product targeting PCSK9 to achieve saturated pharmacological effect in humans.

12–24 weeks after administration, LDL-C reductions exceeding 50% were achieved in most patients, with the highest reduction approaching 70%, representing the best efficacy among global counterparts. Given the ultra-high baseline LDL-C levels of enrolled participants, ART002 has the potential to revolutionize treatment for severe and refractory hypercholesterolemia.

Dr. Yongzhong Wang, Founder and CEO of Accuredit Therapeutics, stated: "The remarkable progress of ART002’s IIT study marks another major milestone following ART001’s approval as the first LNP-based in vivo gene therapy product in both China and the U.S. This further validates the capability of our team’s R&D and industrial strength in gene editing. We will accelerate clinical development to benefit high-risk cardiovascular patients and those with familial hypercholesterolemia."

Dr. Ningru Zhang, Director of The First Affiliated Hospital of Bengbu Medical University, commented: "The advancement of ART002’s clinical study underscores the immense potential of in vivo gene editing for the treatment of chronic diseases. With its unique advantage of ‘one-time treatment, long-term efficacy’, ART002 has the potential to transform the treatment landscape for hypercholesterolemia and related cardiovascular diseases."

ART002:

ART002 utilizes lipid nanoparticles (LNPs) to deliver a single-guide RNA (sgRNA) targeting human PCSK9 and Cas9 mRNA. ART002 specifically recognizes and silences the PCSK9 gene, thereby blocking its interaction with the LDL receptor (LDLR), reducing LDLR degradation, and increasing the number of LDLRs on hepatocyte surfaces. This mechanism effectively lowers plasma LDL-C levels with a single dose. ART002 offers a novel therapeutic option for patients with heterozygous familial hypercholesterolemia (HeFH).

Familial Hypercholesterolemia (FH):

Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder characterized by significantly elevated low-density lipoprotein cholesterol (LDL-C) levels, which markedly increases the risk of atherosclerotic cardiovascular disease (ASCVD) in patients^[1]. FH is categorized into homozygous FH (HoFH) and heterozygous FH (HeFH). HoFH is rare, with a prevalence of 1 in 1–3 million individuals, whereas HeFH affects approximately 1 in 300–500 people. Globally, an estimated 10–20 million individuals are affected by FH^[2]. Current management of FH remains suboptimal, necessitating collaborative efforts among healthcare institutions, industries, and society to improve diagnosis and treatment outcomes for patients.

Founded in 2021, AccurEdit is dedicated to developing and commercializing safe, effective, and target-specific in vivo gene editing therapies, along with delivery technologies, for the treatment of severe or life-threatening genetic and acquired diseases worldwide. AccurEdit is advancing multiple pipeline products. ART001 (ATTR) and ART002 (PCSK9), its first two leading assets, have entered into human clinical trials and both demonstrate the potential to be the Best-in-Class or First-in-class therapies in respective fields.

AccurEdit has established an industry-leading end-to-end technology platform for in vivo gene editing therapies. AccurEdit is the first company in China to advance its LNP-based in vivo gene editing product into human studies and the only company in the world to obtain IND clearances for in vivo gene editing product in both China and the United States.

References:

[1] Carmena R, Roy M, Roederer G, Minnich A, Davignon J. Coexisting dysbetalipoproteinemia and familial hypercholesterolemia. Clinical and laboratory observations. Atherosclerosis. 2000 Jan;148(1):113-24.

[2] Hopkins PN, Toth PP, Ballantyne CM, Rader DJ., National Lipid Association Expert Panel on Familial Hypercholesterolemia. Familial hypercholesterolemias: prevalence, genetics, diagnosis and screening recommendations from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Clin Lipidol. 2011 Jun;5(3 Suppl):S9-17.