Astellas Launches Phase 3 Study of Fezolinetant for VMS in Breast Cancer Patients on Endocrine Therapy

Astellas Pharma Inc. has initiated dosing for the first patient in its Phase 3 HIGHLIGHT 1™ study, investigating the efficacy of fezolinetant. This oral, nonhormonal drug is being tested for the treatment of moderate to severe vasomotor symptoms (VMS) in women with breast cancer undergoing adjuvant endocrine therapy.

Globally, breast cancer remains the most prevalent cancer among women, with approximately 2.3 million new cases reported in 2022. A significant side effect of adjuvant endocrine therapies used in treating breast cancer is the occurrence of VMS, which includes hot flashes and night sweats. These symptoms affect up to 97% of breast cancer patients receiving treatments such as tamoxifen and aromatase inhibitors, and VMS can significantly degrade patients' quality of life and their adherence to treatment regimens.

Marci English, Vice President and Head of BioPharma Development at Astellas, highlighted the importance of the HIGHLIGHT 1 study. She emphasized the current lack of approved treatments for moderate to severe VMS in this patient population and expressed optimism about the potential impact of fezolinetant.

The HIGHLIGHT 1 study is a pivotal clinical trial designed as a randomized, placebo-controlled, double-blind Phase 3 study. It aims to evaluate the safety and efficacy of fezolinetant for treating moderate to severe VMS in women with stage 0 to 3 hormone receptor-positive breast cancer who are on adjuvant endocrine therapy. Approximately 540 participants will be randomized in a 1:1 ratio to receive either fezolinetant or a placebo, across up to 100 global sites. The primary endpoints are changes in the frequency and severity of moderate to severe VMS from baseline to weeks 4 and 12. The study will treat patients for 52 weeks, concluding with a final evaluation at 55 weeks.

Fezolinetant operates by blocking neurokinin B (NKB) binding on the kisspeptin/neurokinin/dynorphin (KNDy) neuron, which helps restore balance in the brain's temperature control center, the hypothalamus. This mechanism aims to reduce both the frequency and intensity of hot flashes and night sweats. Although the safety and efficacy of fezolinetant have not yet been confirmed in this patient group, it represents a promising nonhormonal treatment option currently under investigation.

Astellas Pharma Inc. is a global pharmaceutical company operating in over 70 countries. The company is committed to addressing diseases with high unmet medical needs through its Focus Area Approach, which emphasizes the identification of new drug development opportunities. Beyond traditional pharmaceuticals, Astellas seeks to combine its expertise with advanced technology from various fields to develop innovative healthcare solutions.

The initiation of the HIGHLIGHT 1 study marks a significant step in addressing the unmet needs of women suffering from VMS associated with breast cancer treatments. If successful, fezolinetant could provide a much-needed nonhormonal option for managing these debilitating symptoms, thereby improving both the quality of life and treatment adherence for many patients.

In conclusion, Astellas Pharma Inc.'s ongoing research into fezolinetant through the HIGHLIGHT 1 study signifies an important endeavor to alleviate the burden of VMS for women undergoing adjuvant endocrine therapy for breast cancer. The study's results are highly anticipated and could potentially lead to the first approved treatment specifically targeting moderate to severe VMS in this patient population.