Venetoclax Becomes First BCL-2 Inhibitor Approved in China, Poised to Become AbbVie Blockbuster

Author:Mi Congcong

On December 4, information from the official website of China’s National Medical Products Administration (NMPA) indicated that the application acceptance number for the marketing approval of venetoclax tablets (venetoclax, ABT-199), a BCL-2 inhibitor co-developed by AbbVie and Roche, has been updated to “Approval Completed – Pending Certificate Issuance.”

This means that venetoclax has become the first BCL-2 inhibitor approved for marketing in China. According to earlier information, the approved indication is for use in combination with other drugs to treat newly diagnosed adult patients with acute myeloid leukemia (AML) who are aged 75 years or older, or who have comorbidities that make them unsuitable for intensive induction chemotherapy.

Venetoclax kills cancer cells by binding to and inhibiting Bcl-2, thereby releasing pro-apoptotic proteins. Bcl-2 is one of the key proteins regulating apoptosis; it is overexpressed in various human tumor tissues and cells and is closely associated with tumorigenesis, progression, and drug resistance. The BCL-2 protein has emerged as a novel therapeutic target for hematologic malignancies.

In April 2016, venetoclax was approved by the U.S. FDA for the treatment of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), becoming the first Bcl-2 inhibitor approved globally; in November 2018, venetoclax received approval for the indication of acute myeloid leukemia (AML). Due to its outstanding therapeutic efficacy, venetoclax was granted Breakthrough Therapy Designation by the FDA five times.

According to AbbVie’s financial reports, global sales of Venclexta (venetoclax) were $344 million in 2018 and $792 million in 2019, representing a year-on-year increase of 130%. Sales for the first three quarters of 2020 had already reached $972 million, with annual sales firmly exceeding $1 billion, positioning it as a potential blockbuster product for AbbVie. With the expansion of its indications, sales are expected to continue growing.

According to a Frost & Sullivan report, the global market for apoptosis-targeted therapies was projected to reach $4.9 billion in 2023, with venetoclax remaining the only approved drug worldwide that targets the apoptosis mechanism. Currently, four companies in China have established pipelines targeting Bcl-2, including BeiGene, Fosun Pharma, Ascentage Pharma, and Guangzhou Lupeng Pharmaceuticals, all of which are in early-stage clinical development.

BeiGene’s BGB-11417 is a potential best-in-class Bcl-2 inhibitor, with the promise of overcoming venetoclax-resistant mutations. Fosun Pharma has licensed the exclusive global rights (excluding mainland China, Hong Kong, and Macao) for this class of drugs to Eli Lilly and Company for an upfront payment plus milestone payments totaling $440 million. Ascentage Pharma is the Chinese company with the most advanced development pipeline and the most extensive clinical trials for Bcl-2 inhibitors, boasting three small-molecule targeted Bcl-2 inhibitors.