Farletuzumab Ecteribulin

From a strategic perspective, Bristol-Myers Squibb has been continuously adjusting the priority of its product portfolio in global strategic collaborations, leading to the decision to discontinue MORAb-202. This does not necessarily mean the clinical failure of MORAb-202, but rather that it is of lower priority in the current product mix. Based on available information, MORAb-202 still shows a certain degree of potential.   As for Elahere, one of its main challenges is the limited patient population, as it is only effective for patients with high FRα expression, which accounts for only 35-40% of the ovarian cancer population. Additionally, the safety issues of Elahere, particularly the eye toxicity, which has led to the termination of treatment for one patient due to vision impairment, cannot be ignored. As a result, the FDA has issued a black box warning for Elahere.   In contrast, the data presented at the 2022 ASCO meeting showed that MORAb-202 is also effective for patients with FRα expression below 50% and did not exhibit eye toxicity. Therefore, despite the discontinuation, Daiichi Sankyo remains optimistic about MORAb-202 and plans to prioritize its further development.   However, MORAb-202 also faces challenges. According to the data presented at ASCO, interstitial lung disease/pneumonia is the most common treatment-related adverse event, which is reflected across different dose groups. Although there was only one case of grade 3/4 severity, given the small sample size, the dose optimization and the benefit-risk balance of MORAb-202 still require careful consideration.   In the context of the urgent demand for growth engines, Bristol-Myers Squibb's decision to discontinue MORAb-202, while not directly reflecting its clinical failure, does indicate that the company believes the drug has limited competitiveness. The potential of the FRα-ADC market is vast, but the discontinuation of MORAb-202 further highlights the complexity and uncertainty in this field.   In the FRα-ADC field, the previously perceived "three musketeers" - Elahere, MORAb-202, and STRO-002 - all face their own challenges. The clinical data of STRO-002 did not show the expected advantages, and it also has safety issues such as neutropenia. With the approval of Elahere, the commercial value of STRO-002 has decreased significantly. The discontinuation of MORAb-202 further warns the market that investments and R&D in the FRα-ADC field require a clear-headed approach, objective assessment of early clinical data and significant business development transactions, and adequate preparation to address potential risks and challenges.

Strategic collaboration with Bristol Myers Squibb ended TOKYO, Japan I July 01, 2024 I Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today that it has agreed to end its global strategic collaboration with Bristol Myers Squibb for the co-development and co-commercialization of farletuzumab ecteribulin (FZEC), formerly known as MORAb-202, a folate receptor alpha (FRα)-targeting antibody drug conjugate (ADC) due to ongoing portfolio prioritization efforts within Bristol Myers Squibb. Based on the agreement, Eisai now owns all rights to FZEC and will solely conduct the global development and commercialization of the agent. Eisai will accelerate the development of the agent as a high priority with the hope to deliver it to patients as early as possible. Eisai plans to refund a part of the unused portion of the $200 million payment it received towards research and development expenses from Bristol Myers Squibb under the collaboration agreement and record the remaining as other income. FZEC is Eisai’s first ADC and is composed of Eisai’s in-house developed farletuzumab, a humanized IgG1 monoclonal antibody that binds to the FRα, and Eisai’s in-house developed anticancer agent eribulin, using an enzymatically cleavable linker. Currently, three clinical studies are ongoing: Eisai’s Phase 1/2 study for solid tumors (NCT04300556), and Bristol Myers Squibb’s Phase 2 studies for ovarian, peritoneal and fallopian tube cancers (NCT05613088) and non-small cell lung cancer (NCT05577715). Eisai positions oncology as a key franchise area and aims to contribute toward the cure of cancers by exploring the depths of human biology. FZEC development for refractory cancers is a testament of our dedication to addressing the unmet medical needs of patients with cancer. Eisai will make continuous efforts to increase the benefits provided to patients with cancer and their families. [Notes to editors] 1. Farletuzumab ecteribulin (FZEC, formerly known as MORAb-202) FZEC is Eisai’s first antibody drug conjugate (ADC) and that is composed of Eisai’s in-house developed farletuzumab, a humanized IgG1 monoclonal antibody that binds to the folate receptor alpha (FRα), and Eisai’s in-house developed anticancer agent eribulin, using an enzymatically cleavable linker. After FZEC enters the target FRα-positive cancer cells, it is thought that the linker is enzymatically cleaved, releasing eribulin from the antibody leading to its antitumor activity. When the anticancer agent and antibody components of an ADC are separated inside a targeted antigen-positive cancer cell, it is theorized that the released anticancer agent also has a bystander effect on neighboring antigen-negative cancer cells and the component cells of the tumor microenvironment. In pre-clinical studies, FZEC demonstrated a bystander effect*, with antitumor activity on the FRα-negative cancer cells surrounding the FRα-positive cancer cells. The payload eribulin was the first in the halichondrin class of microtubule dynamics inhibitor. Structurally, eribulin is a simplified and synthetically produced version of halichondrin B, a natural product isolated from the marine sponge Halichondria okadai, and functions by inhibiting the growth phase of microtubule dynamics which prevents cell division. Eribulin has been approved in countries including Japan, the United States, China, in Europe and in Asia for use in the treatment of advanced breast cancer and liposarcoma (soft tissue sarcoma in Japan). *Bystander effect: When the anticancer agent and antibody parts of an ADC are separated inside a targeted antigen-positive cancer cell, the released anticancer agent also affects neighboring antigen-negative cancer cells and the component cells of the cancer microenvironment. SOURCE: Eisai