Bristol Myers Squibb and SystImmune Receive FDA Breakthrough Status for Lung Cancer Drug Iza-bren

The FDA has granted breakthrough therapy designation to Bristol Myers Squibb and SystImmune's experimental drug iza-bren for treating advanced EGFR-mutant lung cancer. Iza-bren is a bispecific antibody-drug conjugate that targets cancer cells. The designation indicates that the drug has shown substantial improvement over existing treatments for this type of cancer.

The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) to Bristol Myers Squibb (NYSE: BMY) and SystImmune's experimental drug, izalontamab brengitecan (iza-bren), for treating locally advanced or metastatic non-small cell lung cancer (NSCLC) with specific epidermal growth factor (EGFR) mutations [1]. This designation is a significant milestone in the development of Iza-bren, highlighting its potential to offer substantial improvements over existing treatments for this type of cancer.

Iza-bren is a bispecific antibody-drug conjugate (ADC) that targets both epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 3 (EGFRxHER3) with a topoisomerase 1 inhibitor payload. The drug is being developed by Biokin in China and jointly by SystImmune and Bristol Myers Squibb outside of China. The FDA's decision was based on efficacy and safety data from three ongoing clinical trials: BL-B01D1-101 and BL-B01D1-203, conducted in China by Sichuan Biokin Pharmaceutical Co., Ltd., and the global BL-B01D1-LUNG-101 study conducted by SystImmune across the United States, Europe, and Japan [1].

The Breakthrough Therapy Designation underscores the potential of Iza-bren to address a critical unmet clinical need. EGFR tyrosine kinase inhibitors (TKIs) have shown clinical efficacy in the frontline setting, but most patients eventually see their cancer progress after about 18 months. Subsequent treatment options often include platinum-based chemotherapy, which are of limited efficacy and come with significant toxicities [1]. The FDA's decision aims to expedite the development and review of drugs that may demonstrate significant benefit over current standards of care.

"The FDA's granting of Breakthrough Therapy Designation underscores the potential of iza-bren to meaningfully improve clinical outcomes for patients with previously treated epidermal growth factor receptor mutation NSCLC," said Dr. Jonathan Cheng, Chief Medical Officer of SystImmune. "The data we have generated to date suggest that iza-bren could address a critical unmet need in patient care, and we look forward to working closely with the FDA to conduct the relevant clinical studies and seek regulatory approval" [1].

Non-small cell lung cancer (NSCLC) accounts for approximately 80% of all lung cancer cases, which remains the leading cause of cancer-related death worldwide. Among patients with NSCLC, 10% to 15% in Western populations and up to 50% in Asian populations harbor activating EGFR mutations [1]. These tumors, most commonly of non-squamous histology, initially respond to EGFR TKIs such as osimertinib. However, resistance is nearly universal, often occurring after about 18 months, and treatment options beyond TKIs and platinum-based chemotherapy provide limited clinical benefit with significant toxicities, highlighting the critical need for new, effective therapies.

Iza-bren's dual mechanism of action blocks EGFR and HER3 signals to cancer cells, reducing proliferation and survival signals. Upon antibody-mediated internalization, the drug's therapeutic payload is released, causing genotoxic stress that leads to cancer cell death [1]. SystImmune, in collaboration with BMS outside of China, is developing Iza-bren (BL-B01D1) with a focus on innovative cancer treatments using its established drug development platforms, focusing on bi-specific, multi-specific antibodies, and antibody-drug conjugates (ADCs) [1].

The granting of Breakthrough Therapy Designation is a significant step forward for Bristol Myers Squibb and SystImmune in their efforts to develop new, effective therapies for advanced EGFR-mutant lung cancer. The designation indicates that the drug has shown substantial improvement over existing treatments for this type of cancer, offering hope for patients who have exhausted other treatment options.

References:
[1] https://www.prnewswire.com/news-releases/izalontamab-brengitecan-egfrxher3-adc-granted-breakthrough-therapy-designation-by-us-fda-for-patients-with-previously-treated-advanced-egfr-mutated-non-small-cell-lung-cancer-302531369.html