Is PCSK9 Small Nucleic Acid Drug the Future of Lipid-Lowering Therapy in China?

With the number of people suffering from dyslipidemia in China soaring to 200 million in 2022 and still on the rise, the potential for lipid-lowering treatments in the country is enormous. Chronic conditions like hyperlipidemia necessitate long-term medication, making the development of effective therapies crucial. Enter PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9), a promising target in the battle against cholesterol, which has garnered significant attention from major pharmaceutical companies.

The discovery of PCSK9's role in binding to LDL receptors and hastening their degradation dates back to 2003. By understanding this mechanism, researchers have been able to envision drug development strategies targeting PCSK9 with greater clarity. The initial entrants in the race for PCSK9 inhibition were monoclonal antibodies, with FDA approvals granted to Repatha (Sanofi/Regeneron) and Praluent (Amgen) in 2015.

While Repatha achieved blockbuster status, generating sales of $1.296 billion, Praluent faced challenges due to patent disputes and accumulated only $527 million in sales over seven years on the market. However, both drugs faced a common hurdle: patient compliance. As chronic disease medications, PCSK9 monoclonal antibodies often require injections every 2-3 weeks to maintain the desired effect, leading to potential issues with long-term adherence.

To address this compliance issue, the emergence of small nucleic acid drugs offers a promising solution. Novartis' Leqvio, a PCSK9siRNA therapy, has demonstrated improved patient adherence. By employing gene silencing techniques to block PCSK9 protein production in the liver, Leqvio delivers a long-lasting therapeutic effect. After an initial course of two injections in the first three months, patients need only one injection every six months to maintain the lipid-lowering effect. Leqvio gained FDA approval in December 2021 and achieved sales of $112 million in its first full year on the market.

The potential demonstrated by the PCSK9 target has attracted the attention of Chinese pharmaceutical companies, prompting them to accelerate their involvement in this field. China's Cinda Biopharmaceuticals has already obtained market approval for its PCSK9 monoclonal antibody, while other companies such as Hengrui Medicine, Kangfang Biotech, and Junshi Biopharmaceuticals are actively seeking regulatory approval, signaling a promising trajectory for their development.

However, beyond monoclonal antibodies, new players are entering the arena with a focus on PCSK9 small nucleic acid drugs, aiming to improve patient compliance. Shengyin Biotech's PCSK9siRNA drug, SGB-3403, gained clinical approval on October 7, while Shipharmaceutical Group's SYH2053, another PCSK9siRNA drug, received clinical approval for the treatment of hypercholesterolemia on November 30.

The latest contender to join the PCSK9 battle is Qilu Pharmaceutical, which recently announced a cooperation agreement with Ribobio. Qilu Pharmaceutical secured the rights and interests of RBD7022, a PCSK9 small nucleic acid drug, for the Chinese market. In exchange, Ribobio will receive over 700 million yuan in down payment and milestone payments.

It appears that the landscape of PCSK9-targeted lipid-lowering drugs in China is shifting from monoclonal antibodies to the realm of small nucleic acids. While Chinese pharmaceutical companies are still in the early stages of research and development in this field, they anticipate facing significant variables in the future.

Could PCSK9 small nucleic acid drugs hold the key to the future of lipid-lowering therapy in China? Only time will tell, as the race for effective treatments continues to unfold.