Lilly’s Verzenio and Amgen’s Blincyto Granted Priority Review in China for Cancer Indications

Text | Zhang Hongli

Recently, the official website of the Center for Drug Evaluation (CDE) under the National Medical Products Administration showed that Eli Lilly's CDK4/6 inhibitor Abemaciclib (Verzenio) and Amgen's bispecific antibody Blinatumomab for injection (trade name: Blincyto) are proposed to be included in the priority review and approval list.

CDK4/6 Inhibitors——Most Promising Targets for Breast Cancer

Breast cancer is the most prevalent malignant tumor among women globally and in China, with its incidence rate increasing year by year and showing a trend toward affecting younger populations. Among breast cancer patients, approximately 70% are estrogen receptor-positive (ER+). Endocrine therapy is the primary treatment modality for these patients; however, the development of endocrine resistance in cases of recurrence or disease progression following endocrine therapy severely impacts subsequent treatment options. Subsequent research has revealed that this type of breast cancer is associated with key cell cycle regulators—cyclin-dependent kinases 4 and 6 (CDK4/6). In ER+ breast cancer, CDK4/6 are overexpressed, leading to uncontrolled cell proliferation and subsequent malignant transformation. Currently, CDK4/6 inhibitors have become an important class of targeted therapeutic agents for the treatment of breast cancer.

The U.S. FDA has approved three CDK4/6 inhibitors: Pfizer’s palbociclib (Ibrance), Novartis’s ribociclib (Kisqali), and Eli Lilly’s abemaciclib (Verzenio). Among these, Ibrance was approved for marketing in China in August 2018 for the treatment of ER-positive, HER2-negative locally advanced or metastatic breast cancer. It is indicated for use in combination with an aromatase inhibitor as initial endocrine therapy in postmenopausal women, under the Chinese brand name Aiboxin.^®。

Eli Lilly’s Verzenio is the third CDK4/6 inhibitor approved by the FDA. It was initially approved by the FDA on September 28, 2017, as monotherapy for the treatment of ER+/HER2- advanced or metastatic breast cancer in patients whose disease has progressed following endocrine therapy and chemotherapy, or in combination with fulvestrant as second-line therapy for HR+/HER2- advanced or metastatic breast cancer in patients whose disease has progressed after endocrine therapy. On February 26, 2018, the FDA approved a third indication for Verzenio: in combination with an aromatase inhibitor as initial endocrine-based therapy for postmenopausal women with HR+/HER2- advanced or metastatic breast cancer. Notably, Verzenio is currently the only CDK4/6 inhibitor that can be used both as monotherapy and in combination regimens.

On November 14, 2019, the marketing application for Abemaciclib was accepted by the Center for Drug Evaluation (CDE), with acceptance numbers JXHS1900144/45/46. The Drug Clinical Trial Registration and Information Publicity Platform indicates that Abemaciclib is currently undergoing three clinical studies in China.

As one of the most promising targets for breast cancer treatment, CDK4/6 inhibitors have attracted significant interest from numerous domestic pharmaceutical companies. According to incomplete statistics, there are currently nine companies in China developing CDK4/6 inhibitors, including Hengrui Medicine (SHR6390), Chia Tai Tianqing (TQB3616), Beta Pharma (BPI-16350), Fosun Pharma, Sihuan Pharmaceutical, CStone Pharmaceuticals, Shanghai Beller Therapeutics, Guangzhou Bestech, and Hansoh Pharmaceutical. Among these, Hengrui Medicine’s SHR6390 is in Phase III clinical trials, leading the pack and poised to become the first domestically produced CDK4/6 inhibitor.

We anticipate that the launch of more CDK4/6 inhibitors, both domestically and internationally, will provide Chinese clinicians and breast cancer patients with a wider range of superior treatment options.

Bispecific Antibodies: The "New Favorite" in New Drug Development

The greatest appeal of bispecific antibodies lies in their mechanism of action. Unlike monoclonal antibodies, bispecific antibodies possess two specific antigen-binding sites (or two different epitopes on a single antigen), enabling them to simultaneously engage target cells and effector cells (typically T cells), thereby enhancing the cytotoxicity against target cells.

Not long ago, a review article on bispecific antibodies was published in Nature Reviews Drug Discovery, which mentioned that as of March 2019, there were approximately 85 bispecific antibodies in clinical development. However, most bispecific antibodies are currently in early-stage clinical trials, with the primary research focus still concentrated on oncology (86%).

Initiation of Clinical Studies on Bispecific Antibodies, 2010–2018

Bispecific Antibody Clinical Pipeline

In 2009, catumaxomab, developed by Trion GmbH, received approval from the European Medicines Agency (EMA) for the treatment of malignant ascites, becoming the first bispecific antibody approved for marketing worldwide. However, due to commercial failure, the drug performed poorly after launch and was ultimately withdrawn from the market and discontinued in 2017. Currently, the two approved bispecific antibodies available on the market are Amgen’s Blincyto and Roche’s emicizumab. Blincyto is indicated for pediatric and adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia, while Hemlibra is used for the treatment of hemophilia A.

Approved Bispecific Antibodies

In December 2018, Hemlibra received accelerated approval from the National Medical Products Administration (NMPA), becoming the first bispecific antibody drug marketed in China. On October 29, 2019, the Center for Drug Evaluation (CDE) accepted the marketing application for Amgen’s blinatumomab for injection, with the acceptance number JXSS1900060.

In China, according to incomplete statistics from Sina Medicine, there are currently 14 bispecific antibody drugs from 9 companies that have entered the clinical/IND stage. Among them, Innovent Biologics has 3 drugs, while Alphamab Oncology, Genor Biopharma, and Wuhan YZY Biopharma each have 2 drugs.

Bispecific Antibodies in Clinical/IND Stage in China

In addition to those listed in the table above, public information indicates that nearly 20 other companies in China, including 3SBio, Chia Tai Tianqing, Livzon Pharmaceutical, Hisun Pharmaceutical, Simcere Pharmaceutical, Anke Biotechnology, I-Mab Biopharma, Brii Biosciences, Adagene, and Harbour BioMed, have also established a presence in the bispecific antibody field.

Excluding those already on the market, there are only two bispecific antibodies in the global pipeline that have entered Phase III clinical trials: Asciminib (ABL001) from the South Korean biotechnology company ABL Bio, and faricimab (RG7716) from Roche/Genentech. Therefore, domestic companies and drug candidates with faster progress still have significant opportunities.