Johnson & Johnson's EGFR/c-Met Bispecific Antibody Gains FDA Approval, Kite-SciClone’s CAR-T Therapy for Multiple Myeloma Approved in China, and YolTech’s In Vivo Gene Editing Drug Enters Clinical Trials

A Total of 3 Briefs | Estimated Reading Time: 5 Minutes◆◆ ◆

01

Johnson & Johnson's EGFR/c-Met Bispecific Antibody Approved by FDA for First-Line Treatment of NSCLC

On March 1, Johnson & Johnson announced that after priority review, the FDA had approved Rybrevant (amivantamab-vmjw) in combination with chemotherapy (carboplatin-pemetrexed) as a first-line treatment for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations. This FDA action also converted Rybrevant's accelerated approval from May 2021 into a full approval based on the confirmatory Phase III PAPILLON study.

The press release shows that Rybrevant is the first targeted therapy approved by the FDA for first-line treatment of NSCLC patients with EGFR exon 20 insertion mutations.

PAPILLON Study

The results showed that, compared with chemotherapy alone, the combination of Rybrevant and chemotherapy reduced the risk of disease progression or death by 61%, and improved ORR and PFS. Based on the data from the PAPILLON study, the National Comprehensive Cancer Network (NCCN) updated the NCCN Clinical Practice Guidelines, recommending Rybrevant in combination with chemotherapy as the preferred first-line treatment regimen for patients with EGFR exon 20 insertion-mutated NSCLC.

Rybrevant is a bispecific antibody that targets EGFR resistance mutations, MET mutations, and amplifications. It can simultaneously bind to the extracellular structures of EGFR and c-Met, block the binding of ligands to EGFR and MET, promote receptor degradation, and trigger antibody-dependent cellular cytotoxicity.

In May 2021, based on data from the Phase I CHRYSALIS study cohort of Rybrevant monotherapy, the product received accelerated FDA approval for the treatment of metastatic NSCLC patients with EGFR exon 20 insertion mutations who progressed after platinum-based chemotherapy. In December of the same year, Rybrevant received conditional approval in the European Union.

In November 2023, Johnson & Johnson submitted a supplemental Biologics License Application (sBLA) to the FDA for Rybrevant, to be used in combination with chemotherapy for the treatment of patients with EGFR-mutated non-small cell lung cancer (NSCLC) whose disease has progressed during or after treatment with Osimertinib. In December 2023, Johnson & Johnson submitted a new indication marketing application for Rybrevant to the FDA and EMA in the United States and Europe, respectively, for first-line treatment in combination with the third-generation EGFR inhibitor Lazertinib in patients with locally advanced or metastatic EGFR-mutated NSCLC.

In October 2023, Johnson & Johnson submitted the first marketing application for Rybrevant to NMPA, with the potential to launch in China by Q4 2024.

Source: PharmaCube

02

China's Fifth CAR-T Therapy Approved: CARsgen Therapeutics' New Drug for Multiple Myeloma Gains Approval

On March 1, CARsgen Therapeutics (2171.HK) announced that the drug Zevor-cel Injection has been approved for marketing by the National Medical Products Administration.

As a CAR-T cell product targeting BCMA (fully human anti-autologous B-cell maturation antigen), the approval of Zevor-cel injection is for the treatment of adult patients with relapsed or refractory multiple myeloma (R/R MM) who have progressed after receiving at least three prior lines of therapy (including at least one proteasome inhibitor and one immunomodulatory agent).

It is worth mentioning that this is the fifth CAR-T cell product to be launched in China.

Prior to this, Fosun Kite's Axicabtagene Ciloleucel Injection, Wuxi Jono (2126.HK)'s Relmacabtagene Autoleucel Injection, IASO Bio/Innovent Biologics (1801.HK)'s Ebcartagene Autoleucel Injection, and Hopstem Biotech's Nacartagene Autoleucel Injection have been successfully approved for marketing in China.

In terms of target points, this is the second CAR-T cell product targeting BCMA in China, following the injection of Idecabtagene Vicleucel.

At the same time, both Zevorcel Injection and Idecabtagene Vicleucel Injection are targeting the R/R MM indication.

Among them, multiple myeloma is a refractory malignant plasma cell disease, accounting for about 10% of hematological tumors.

Frost & Sullivan expects that the number of patients with multiple myeloma in China will be approximately 153,000 in 2023, and may increase to 266,300 by 2030.

Currently, CARsgen Pharma has granted Huadong Medicine (000963.SZ) the exclusive commercialization rights of Zevor-cel Injection in mainland China. In addition to paying an upfront payment of 200 million yuan, Huadong Medicine will also pay up to 1.025 billion yuan in registration and sales milestone payments.

However, the commercial success of Zevorcel Injection remains a question mark.

On the one hand, the potential risks of CAR-T therapy are drawing attention from regulatory authorities.

In January 2024, the FDA required that the approved CAR-T cell therapy products add "the risk of secondary T-cell lymphoma after treatment" to their black box warnings. Regulatory authorities in China also followed the FDA's lead in issuing risk alerts for CAR-T products.

However, some studies suggest that the risk of developing a second cancer after CAR-T cell therapy is relatively low. (Note: A black box warning is a requirement by the FDA for pharmaceutical companies to include a statement in the drug's instructions regarding warnings about adverse drug reactions.)

Recently, researchers from the Perelman School of Medicine at the University of Pennsylvania reported in the journal *Nature Medicine* that an analysis of more than 400 patients treated at the University of Pennsylvania’s Perelman School of Medicine found that developing any type of second cancer following CAR-T cell therapy is rare.

Wall Street News·Insight Team believes that although CAR-T therapy carries associated risks, relevant studies suggest that such risks have limited impact on patients. The approval of Zevor-cel injection by Carsgen Therapeutics marks the first CAR-T product approved since the black box warning, indicating that regulatory authorities still consider the benefits of CAR-T therapy to far outweigh the risks for patients.

On the other hand, the high cost of CAR-T therapy persists, with the selling prices of CAR-T cell products already available in China mostly in the millions, which limits the accessibility of the drugs and poses certain obstacles to their commercialization.

CARsgen Pharma is currently seeking to expand the market for Zevor-cel Injection overseas. The company is advancing a Phase 1b/2 clinical trial in North America to evaluate the safety and efficacy of Zevor-cel Injection for the treatment of R/R MM.

无论如何，此番泽沃基奥仑赛注射液的上市里程碑对于科济药业来说都有重要意义——科济药业完成了管线商业化的第一步，摘掉“0收入”的帽子。

With the promotion capabilities of Huadong Medicine, whether Zevorcel Injection can achieve greater commercial success is something the market is watching closely.

However, the market's expectations for CARsgen Therapeutics are more focused on breakthroughs in solid tumors. Currently, the company’s humanized Claudin18.2-targeted CAR-T product “CT041,” which is mainly used to treat gastric cancer, pancreatic cancer, etc., is in Phase II/III clinical trials.

Source: Wall Street News

03

Yao Tang Biotech's In Vivo Gene Editing Drug Approved for Clinical Trials

On March 1, YolTech Therapeutics announced that the Investigational New Drug (IND) application for its self-developed first in vivo gene editing drug, YOLT-201, has been approved by the Center for Drug Evaluation (CDE) of the China National Medical Products Administration. This marks the entry of the candidate drug into the registrational clinical development stage. The indication under development for YOLT-201 Injection is transthyretin amyloidosis (ATTR).

Screenshot source: CDE official website

ATTR is a fatal disease caused by the instability of transthyretin (TTR) tetramers, leading to abnormal folding of monomers and the formation of amyloid deposits. These amyloid fibrils gradually accumulate in multiple tissues and organs, particularly in the heart and nervous system, severely impacting patients' quality of life. Currently, there is a lack of effective treatment options. The proposed indication for development of YOLT-201 injection is ATTR, including transthyretin amyloidosis polyneuropathy (ATTR-PN) and transthyretin amyloid cardiomyopathy (ATTR-CM).

According to the press release from Yaotang Biotech, YOLT-201 utilizes in vivo gene editing technology and lipid nanoparticle (LNP) delivery technology. The gene editing tool it contains can achieve highly efficient and specific knockdown of the TTR target gene in the human liver, with the potential to reduce TTR protein levels in the blood for life after a single administration. Previously, YOLT-201 had already initiated an investigator-initiated clinical study (IIT) in December 2023 and completed dosing for the first three subjects, achieving excellent preliminary clinical data.

It is reported that the approved YT-YOLT-201-101 is a multi-center, open-label, single-dose phase 1/2a clinical study, aimed at evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of YOLT-201 in patients with ATTR-PN and ATTR-CM. This trial is divided into two phases: the first phase is an open, single-dose, dose-escalation trial to determine the optimal biological dose (OBD) of YOLT-201; the second phase is an open, single-dose, dose-expansion trial to preliminarily assess the safety and initial efficacy of YOLT-201 at the OBD.

Dr. Wu Yuxuan, founder of Yaotang Biotech, stated: "The approval of YOLT-201 for clinical trials is a milestone event for Yaotang Biotech in the field of in vivo gene editing. In the previous IIT clinical study conducted at the First Affiliated Hospital of Zhejiang University School of Medicine, encouraging preliminary efficacy and safety results were achieved: TTR levels in patients treated with YOLT-201 significantly decreased, and no drug-related adverse reactions above grade 2 occurred during the entire treatment and follow-up process. Yaotang Biotech is highly confident in the clinical prospects of YOLT-201. We will continue to make relentless efforts to advance the innovative development of in vivo gene editing drugs, providing patients with safer and more effective gene therapy solutions."

Yao Tang Bioscience was founded in July 2021, focusing on in vivo gene editing technology and developing a new generation of in vivo gene editing drugs through the mRNA-LNP delivery system. According to Dr. Yu-Xuan Wu, founder of Yao Tang Bioscience, in a previous interview with the content team of WuXi AppTec: "We hope to combine LNP-mRNA in vivo delivery technology with gene editing technology. Through the continuous development and optimization of CRISPR, base editing, and other next-generation gene editing tools, as well as innovative improvements in the production process of next-generation LNP-mRNA drugs, we aim to develop a new generation of more efficient and safer in vivo gene editing drugs, bringing entirely new treatment options for genetic diseases, metabolic diseases, and infectious diseases."

Source: MedView

Editor: Ren Luyun

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