Accutar Biotechnology's AC699, an investigational orally bioavailable chimeric degrader of estrogen receptor (ER) α, has received Fast Track designation from the U.S. Food and Drug Administration (FDA) for the treatment of patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor-2 (HER2)-negative, estrogen receptor 1 (ESR1)-mutated advanced or metastatic breast cancer following progression on at least one line of endocrine-based therapy.
Clinical Significance
ER-positive/HER2-negative breast cancer is the most prevalent subtype, accounting for approximately 70% of all breast cancer cases. Among patients with this subtype who have received endocrine therapy in the metastatic setting, mutations in the ESR1 gene are common, occurring in 20-40% of cases. The Fast Track designation underscores the FDA's recognition of the unmet medical need for effective treatments in this patient population.
AC699: Mechanism and Early Clinical Data
AC699 is designed to selectively degrade both wild-type and mutant forms of ERα. Preliminary data from an ongoing Phase 1 trial (NCT05654532), presented at ASCO 2024, demonstrated an objective response rate (ORR) of 50% in patients with ESR1 mutations. This early evidence suggests that AC699 could provide a meaningful clinical benefit for patients who have progressed on existing endocrine therapies.
Fast Track Designation Benefits
The FDA's Fast Track program aims to expedite the development and review of drugs that treat serious conditions and address unmet medical needs. Benefits of this designation include more frequent meetings and communication with the FDA, as well as the potential for accelerated approval and priority review if relevant criteria are met. This designation should help Accutar Biotechnology to optimize and accelerate the development program.
Ongoing Phase 1 Trial Details
The Phase 1 multi-center, open-label study (AC699-001) is evaluating the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of AC699 in patients with ER-positive/HER2-negative locally advanced or metastatic breast cancer. Additional information on this clinical trial can be found on www.clinicaltrials.gov.
