The U.S. Food and Drug Administration has granted orphan drug designation to VT3989 for the treatment of mesothelioma, marking a significant regulatory milestone for Vivace Therapeutics' first-in-class cancer therapeutic. The designation supports development of treatments for rare diseases affecting fewer than 200,000 people in the United States and provides benefits including tax credits for clinical trials, FDA fee exemptions, and up to seven years of market exclusivity after approval.
Novel Mechanism Targets Hippo Pathway
VT3989 represents a first-in-class transcriptional enhanced associate domain (TEAD) autopalmitoylation inhibitor designed to target the Hippo pathway. The experimental cancer treatment works by blocking palmitoylation in TEAD proteins, which are part of the Hippo pathway that helps control how cells grow and divide. When this pathway doesn't work properly, it can lead to cancer development.
"The granting of Orphan Drug Designation to VT3989 underscores the critical need for new, effective therapies for mesothelioma, an aggressive cancer with limited treatment options," said Sofie Qiao, president and chief executive officer of Vivace Therapeutics. "The benefits provided by this important designation will support our continued advancement of VT3989, which has already generated compelling clinical trial data, a first for this promising therapeutic class."
Promising Clinical Results in Phase 1 Study
VT3989 has demonstrated encouraging clinical activity and a favorable safety profile in an ongoing open-label Phase 1 study involving more than 200 patients. The drug is the first and only member of the TEAD autopalmitoylation inhibitor class for which compelling clinical efficacy data have been publicly reported, according to the company.
Results have been particularly notable in patients with mesothelioma whose cancer progressed after chemotherapy and immunotherapy, which represent the only approved treatments for this disease. The Phase 1 multi-center, open-label study evaluated the safety, tolerability, pharmacokinetics, and biological activity of VT3989 in patients with metastatic solid tumors that had not responded to treatment, including pleural and non-pleural malignant mesothelioma.
Comprehensive Trial Design
The Phase 1 study included three distinct phases. The dose escalation phase used a traditional 3+3 design, testing the drug dose in groups of three patients and increasing the dose if side effects were limited to assess safety until the maximum tolerated dose or recommended Phase 2 dose and schedule were identified. The maximum tolerated dose was defined as the highest dose at which fewer than 33% of patients experienced a dose-limiting side effect during the first treatment cycle.
The dose expansion phase further evaluated safety and early antitumor activity at the recommended dose across up to six cohorts, including patients with mesothelioma of any site, non-pleural mesothelioma, pleural mesothelioma, and solid tumors with specific genetic alterations. In the combination phase, mesothelioma patients received VT3989 with immunotherapy drugs nivolumab and ipilimumab, while patients with non-small cell lung cancer and EGFR mutations received VT3989 with targeted therapy osimertinib.
Path to Registration
Vivace Therapeutics has committed to continuing clinical development of VT3989 and plans to discuss moving into a registrational Phase 3 study in mesothelioma with the FDA by the end of 2025. Additional findings from the ongoing Phase 1 study will be presented at a major medical meeting in late 2025.
The San Francisco Bay Area-based company has raised $105 million to date and focuses on targeting the Hippo pathway through a first-in-class approach to treat human carcinomas with high unmet medical needs.
