IDEAYA Biosciences announced today that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation (BTD) for darovasertib monotherapy in the neoadjuvant treatment of adult patients with primary uveal melanoma (UM) for whom enucleation has been recommended.
The designation enables expedited development and priority regulatory review for darovasertib, a potential first-in-class protein kinase C (PKC) inhibitor, addressing a significant unmet medical need in a patient population with no FDA-approved systemic therapies.
Clinical Evidence Supporting the Designation
The BTD application was supported by updated interim clinical data from an ongoing Phase 2 open-label trial (NCT05907954) evaluating darovasertib monotherapy in the neoadjuvant setting for localized UM.
In September 2024, IDEAYA presented interim clinical data demonstrating an 82% ocular tumor shrinkage rate and a 61% eye preservation rate in UM patients. The updated clinical data submitted as part of the BTD application included comprehensive assessments of efficacy, safety, radiation reduction, eye preservation, and vision preservation/improvement on treatment.
"We are pleased to receive FDA Breakthrough Therapy designation as we prepare to advance neoadjuvant darovasertib into a potential Phase 3 registrational trial in patients with primary UM," said Dr. Darrin Beaupre, Chief Medical Officer of IDEAYA Biosciences. "This designation highlights the potential of monotherapy darovasertib in a patient population with significant unmet medical need where there are currently no FDA-approved systemic therapies."
Development Timeline and Market Potential
IDEAYA intends to initiate a Phase 3 randomized registrational trial in neoadjuvant UM in the first half of 2025. The company plans to present multiple clinical data updates in neoadjuvant UM and metastatic uveal melanoma (MUM), including median overall survival (mOS) from the Phase 2 study (IDE196-001), at medical conferences in mid-year 2025 and the second half of 2025.
The potential Phase 3 registrational study would evaluate neoadjuvant darovasertib in primary UM patients who are eligible for enucleation (Cohort 1) or plaque brachytherapy (Cohort 2). Neoadjuvant UM has a projected annual incidence for North America, Europe, and Australia of approximately 12,000 patients.
Expanding Regulatory Recognition
This BTD designation follows the Fast Track designation previously granted by the FDA for evaluation of darovasertib in combination with crizotinib in adult patients being treated for metastatic uveal melanoma (MUM). A Phase 2/3 registration-enabling trial of the darovasertib and crizotinib combination in first-line HLA-A2-negative MUM is currently ongoing, with a median progression-free survival readout targeted by year-end 2025.
Darovasertib has also been designated as an Orphan Drug by the FDA in UM, including in MUM, entitling IDEAYA to certain potential tax credits, exemptions from user fees, and statutory marketing exclusivity.
Significance of Breakthrough Therapy Designation
The Breakthrough Therapy designation is designed to expedite the development and regulatory review of promising therapies for serious or life-threatening conditions where preliminary clinical evidence suggests substantial improvement over existing treatments. The designation facilitates more intensive FDA guidance, cross-disciplinary collaboration, and eligibility for rolling submission and priority review.
In pre-market activity following the announcement, IDEAYA shares gained approximately 2.6 percent on the Nasdaq, reflecting investor confidence in the company's development program.
About Uveal Melanoma
Uveal melanoma is a rare but aggressive form of eye cancer that develops in the uveal tract, which includes the iris, ciliary body, and choroid. Current treatment options for primary UM are limited, with many patients facing the prospect of eye removal (enucleation) or radiation therapy, which can lead to significant vision loss and other complications.
The development of darovasertib represents a potential paradigm shift in the management of primary UM, offering the possibility of tumor shrinkage and eye preservation for patients who would otherwise face enucleation.
About IDEAYA Biosciences
IDEAYA is a precision medicine oncology company committed to the discovery and development of targeted therapeutics for patient populations selected using molecular diagnostics. The company's approach integrates capabilities in identifying and validating translational biomarkers with drug discovery to select patient populations most likely to benefit from its targeted therapies.
With darovasertib's Breakthrough Therapy designation, IDEAYA continues to advance its mission of developing innovative treatments for patients with high unmet medical needs in oncology.
