CARsgen Therapeutics Announces First CAR-T Product SaiKaiZe (Zevor-cel) Approved in China for Relapsed/Refractory Multiple Myeloma

On March 1, CARsgen Therapeutics announced that the National Medical Products Administration (“NMPA”) has formally approved the New Drug Application (“NDA”) for CYCLOVIR® (zevorcabtagene autoleucel injection, product code: CT053, an autologous anti-BCMA CAR-T candidate therapy) for the treatment of adult patients with relapsed or refractory multiple myeloma who have progressed after at least three prior lines of therapy (including at least one proteasome inhibitor and one immunomodulatory agent).

Professor Chen Wenming, Chief Physician of the Department of Hematology at Beijing Chaoyang Hospital and Principal Investigator for the Chinese registrational clinical trials of Cykafree®, stated, “Under conventional treatment modalities, patients with relapsed or refractory multiple myeloma have a poor prognosis and limited therapeutic options. There is a significant unmet clinical need in this patient population, with an urgent demand for effective, safe, and convenient treatment approaches. The approval of Cykafree® provides clinicians with additional therapeutic choices and brings new hope to patients.”

Professor Fu Chengcheng, Chief Physician of the Department of Hematology at The First Affiliated Hospital of Soochow University and Principal Investigator of the Chinese registrational clinical trials for Cycaze®, stated, “Based on the published results of the LUMMICAR-1 study, Cycaze® has demonstrated deep and durable efficacy in patients with relapsed or refractory multiple myeloma, with a favorable overall tolerability profile. We are greatly encouraged by the successful approval and market launch of Cycaze®, and we look forward to its future availability benefiting more patients, helping them achieve high-quality long-term survival.”

Dr. Zonghai Li, Founder, Chairman of the Board, Chief Executive Officer, and Chief Scientific Officer of CARsgen Therapeutics, stated, “On the occasion of CARsgen’s tenth anniversary, I am delighted to announce the successful approval and market launch of Carvykti® (cilta-cel). This represents a significant milestone in our company’s development journey and serves as the best reward for our team’s relentless efforts. I extend my heartfelt gratitude to our team members, investigators, patients, and all sectors of society for their support and trust. We look forward to Carvykti® bringing greater hope to adult patients with relapsed or refractory multiple myeloma and improving their survival outcomes. Upholding our vision of ‘Innovating Science to Benefit Humanity,’ we will continue to explore new technologies, expand our product pipeline with global rights, address major challenges facing CAR-T cell therapies, and deliver innovative and differentiated cell therapies to cancer patients worldwide.”

SaiKaize® is an autologous BCMA-targeted CAR-T cell product generated through lentiviral transduction of T cells. The lentivirus-encoded CAR comprises a fully human BCMA-specific single-chain variable fragment (“scFv”), a human CD8α hinge domain, a CD8α transmembrane domain, a 4-1BB co-stimulatory domain, and a CD3ζ activation domain. The proprietary novel fully human scFv exhibits high binding affinity and stability.

In 2019, Cycaze® was granted Regenerative Medicine Advanced Therapy (RMAT) designation and Orphan Drug designation by the U.S. FDA. It subsequently received Priority Medicines (PRIME) designation and Orphan Drug Product designation from the European Medicines Agency (EMA) in 2019 and 2020, respectively. In China, Cycaze® was included in the National Medical Products Administration’s (NMPA) Breakthrough Therapy Drug list in 2020. CARsgen Therapeutics is currently advancing a Phase 1b/2 clinical trial (LUMMICAR STUDY 2) in North America to evaluate the safety and efficacy of Cycaze® for the treatment of relapsed or refractory multiple myeloma.

In October 2022, the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) accepted the marketing application for zevorcabtagene autoleucel injection and granted it priority review for the treatment of relapsed/refractory multiple myeloma.

The approval of Saikaze® was based on an open-label, single-arm, multicenter Phase II clinical trial conducted in China (LUMMICAR STUDY 1, NCT03975907). According to the data from the pivotal Chinese Phase II clinical study presented at the 2022 American Society of Hematology (ASH) Annual Meeting, Saikaze® demonstrated encouraging efficacy and a favorable safety profile.

Multiple myeloma is a refractory malignant plasma cell disorder, accounting for approximately 10% of all hematologic malignancies.¹ With the accelerating aging population and increasing life expectancy in China, the number of patients with multiple myeloma continues to rise. According to Frost & Sullivan estimates, the prevalent population of multiple myeloma in China was approximately 153,000 in 2023, with 23,200 new cases. The prevalent population is projected to grow to 266,300 by 2030.

In January 2023, CARsgen Therapeutics and Huadong Medicine entered into a commercialization collaboration for Cykabe® in mainland China, with CARsgen Therapeutics granting Huadong Medicine exclusive commercialization rights for Cykabe® in mainland China. Under the terms of the agreement, CARsgen Therapeutics will receive an upfront payment of RMB 200 million and is eligible to receive regulatory and sales milestone payments totaling up to RMB 1.025 billion.

CARsgen Therapeutics is a biopharmaceutical company with operations in China and the United States, primarily focused on innovative chimeric antigen receptor T-cell (CAR-T) therapies for the treatment of solid tumors and hematologic malignancies.

CT053, the company’s most advanced pipeline candidate, has received approval. Additionally, CARsgen Therapeutics’ solid tumor candidate CT041 is in confirmatory Phase II clinical trials, CT011 is in Phase I clinical trials, and AB011 is in Phase Ib clinical trials.

On December 12, 2023, CARsgen Therapeutics issued an announcement stating that the FDA had halted clinical trials for its three CAR-T therapy candidate products. The following day, CARsgen’s stock price plummeted.

According to CARsgen Therapeutics, the FDA did not raise questions regarding the company’s clinical data. The FDA’s professional recommendations primarily addressed issues related to Chemistry, Manufacturing, and Controls (CMC), including the need for compliance improvements in certain legacy areas such as employee training, rather than concerns about manufacturing processes. In its announcement, CARsgen Therapeutics also stated that it would conduct a comprehensive review and improvement of its current Good Manufacturing Practice (cGMP) systems and committed to working closely with the FDA to resolve issues identified during the inspection, thereby ensuring the smooth progress of clinical trials and marketing applications as well as high-quality production.

However, the challenges facing CAR-T therapy do not end there. In November 2023, the U.S. Food and Drug Administration (FDA) issued a public announcement on its website stating that all approved CAR-T therapies targeting BCMA and CD19 carry a risk of inducing T-cell malignancies, including chimeric antigen receptor (CAR)-positive lymphomas. The FDA further stated that although the overall health benefits of these products in their approved indications continue to outweigh their potential risks, the agency is still investigating the risk of T-cell malignancies associated with these products, including cases requiring hospitalization and resulting in death, and is evaluating the need for regulatory action.

It is worth noting that, judging by the reaction in the secondary market, listed companies with commercialized CAR-T-related products have been much less affected. CAR-T therapies are often referred to as “sky-high-priced drugs.” In contrast, the stock prices of listed companies without commercialized CAR-T products have clearly suffered a heavier impact.

At that time, CARsgen Therapeutics, which had no commercially available CAR-T products, was forced to endure the pressures of sustained losses and stock price volatility. Behind these continuing losses, the company pinned high hopes on zevor-cel (CT053; marketed as Saikaize®), whose clinical trials had been halted.

The approval and launch of Saikaize® will undoubtedly drive growth in CARsgen Therapeutics’ performance.