On April 30, 2024 Shenzhen Chipscreen Biosciences Co., Ltd. (Chipscreen Biosciences, Stock Symbol: 688321.SH) reported that the company’s lead innovative product Chidamide (Epidaza) , an oral subtype-selective histone deacetylase (HDAC) inhibitor, combined with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), has been officially approved by the National Medical Products Administration (NMPA) for treatment of previously untreated diffuse large B-cell lymphoma (DLBCL) with positive MYC and BCL2 expression (Press release, Shenzhen Chipscreen Biosciences, APR 30, 2024, View Source [SID1234642479]). Up to now, Chidamide has been approved for multiple indications globally. (For more information, please review the global commercialization situation).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma, with approximately 30000 new cases occurring annually in China. Clinical diagnosis and treatment guidelines and consensus both domestically and internationally recommend the R-CHOP regimen as the standard first-line treatment for DLBCL. However, about one-third or more of patients in the overall population still experience ineffective or early recurrence of first-line R-CHOP treatment. Meanwhile, approximately 30% of patients with DLBCL exhibit simultaneous overexpression of MYC/BCL2 protein (referred to as "double expression" lymphoma, DEL), and their efficacy and prognosis after R-CHOP treatment are significantly lower than those of non double expression patients. Therefore, how to combine new drugs based on R-CHOP regimen to provide a more effective and safer treatment to our patients is a significant unmet medical need.

The approval of this new indication is based on a randomized, double-blind, placebo-controlled, multicenter Phase III clinical trial DEB trial (NCT04231448). The DEB trial is the first Phase III registered clinical study in the world as first line treatment of MYC/BCL2 dual expression diffuse large B-cell lymphoma. This trial is to evaluate the efficacy and safety of Chidamide combined with R-CHOP compared to R-CHOP in primary treatment and MYC/BCL2 dual expression DLBCL subjects. Based on the interim analysis conducted by the Independent Data Monitoring Committee (iDMC), the efficacy and safety indicators set by the protocol were achieved. Compared with the R-CHOP regimen, the Chidamide combination regimen significantly improved the complete response rate (CRR) of the study’s key secondary endpoint, and the study’s primary endpoint, event free survival (EFS), also showed a clear trend of benefit. The experimental safety profile is consistent with known risks, and no new significant safety signals were found. The results of the interim analysis of the DEB Phase III study were selected as the Late breaking Abstract (LBA) for the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on April 24, 2024.

Dr. Xianping Lu, Chairman and General Manager of Chipscreen Biosciences, stated, "The classic R-CHOP regimen has been used as a first-line treatment for diffuse large B-cell lymphoma (DLBCL) for nearly 20 years, but its therapeutic effect is not satisfactory in populations with dual expression of BCL2 and MYC proteins. The combination of Chidamide and R-CHOP is the world’s first phase 3 registered clinical study that focuses on first line therapy of dual expressed DLBCL, and also the world’s first R-CHOP improvement study with significant benefits in complete remission rate. We believe that the approval of the new indication will bring new hope and better survival benefits to patients."

About Chidamide (Epidaza)

Chidamide (Tucidinostat, Trade name: Epidaza), a Class 1.1 innovative drug, is a novel molecular entity with global patent protection and the first marketed product developed independently by Chipscreen Biosciences. The first original chemical new drug approved in China, Chidamide is also the first oral subtype-selective histone deacetylase (HDAC) inhibitor in the world, Since its approval in China in December 2014 for the treatment of peripheral T-cell lymphoma, Chidamide has achieved significant commercialization worldwide and continuously explored new indications.

Global commercialization situation:

In December 2014, Chidamide was approved for use in patients with recurrent or refractory peripheral T-cell lymphoma (PTCL) in China;
In November 2019, Chidamide was approved to combine aromatase inhibitors to treat locally advanced or metastatic breast cancer patients with estrogen receptor positive, human epidermal growth factor receptor-2 negative, postmenopausal, and endocrine therapy relapse or progress in China;
In June 2021, Chidamide was approved for monotherapy in the treatment of recurrent or refractory (R/R) adult T-cell leukemia (ATL) in Japan;
In December 2021, Chidamide was approved for monotherapy for recurrent or refractory (R/R) peripheral T-cell lymphoma (PTCL) in Japan;
In March 2023, Chidamide was approved to be used for postmenopausal women with locally advanced or metastatic breast cancer who are hormone receptor positive, type II human epidermal growth factor receptor (HER2) negative, and relapse or worsen after endocrine therapy (in combination with exemestane) in Taiwan, China;
In April 30, 2024, Chidamide was approved to use in combination with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) for previously untreated diffuse large B-cell lymphoma (DLBCL) patients with positive MYC and BCL2 expression in China.
Global exploration of other indications:

In addition to ongoing global multicenter phase III clinical trial for the first-line treatment of melanoma in comniation with Opdivo, Chidamide is also conducting multiple clinical trials in China and internationally in combination with different anti-tumor immunotherapies.
In November 2023, the Phase II clinical trial of the first-line treatment of non-small cell lung cancer with Chidamide combined with Tislelizumab was completed and enrolled.
On March 4, 2024, Professor Ruihua Xu and Professor Feng Wang from the Cancer Prevention and Treatment Center of Sun Yat sen University led the research on CAPAbility-01, which was published on the world’s top academic journal Nature Medicine (IF=82.9). As one of the most valuable sub journals under Nature, the publication of Nature Medicine reflects the academic authority’s recognition of CAPAbility-01 research. This study indicates that for patients with microsatellite stable/mismatched repair function intact (MSS/pMMR) type metastatic colorectal cancer (mCRC), a three drug regimen led by Chidamide (Chidamide+sintilimab antibody+bevacizumab) for third line and above treatment, with an 18 week PFS rate of 64.0%, an ORR of 44.0%, and a median PFS of 7.3 months, is considered a promising treatment option for MSS/pMMR advanced CRC patients.
On April 24, 2024, an abstract entitled "Tucidinostat plus R-CHOP in previously untreated diffuse large B-cell lymphoma with double expression of MYC and BCL2: An interim analysis from the phase III DEB study" was selected the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) LBA list for the 2024 ASCO (Free ASCO Whitepaper), which submitted by Professor Weili Zhao’s team from Ruijin Hospital affiliated with Shanghai Jiao Tong University School of Medicine