FDA Grants Orphan Drug Status to VT3989 for Mesothelioma Treatment

The FDA awarded orphan drug designation to VT3989 for mesothelioma: © stock.adobe.com.

The U.S. Food and Drug Administration (FDA) has granted orphan drug designation to VT3989 for the treatment of mesothelioma in the U.S., according to a news release from Vivace Therapeutics.

VT3989 is an experimental cancer treatment that works by blocking a process called palmitoylation in a group of proteins known as TEAD. These proteins are part of the Hippo pathway, which helps control how cells grow and divide. When this pathway doesn’t work properly, it can lead to cancer. By targeting TEAD proteins, VT3989 aims to shut down signals that allow cancer cells to grow.

Orphan drug designation, granted by the FDA, supports development of treatments for rare diseases affecting fewer than 200,000 people in the U.S. The designation offers benefits such as tax credits for eligible clinical trials, FDA fee exemptions, and up to seven years of market exclusivity after approval.

"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. 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," Sofie Qiao, president and chief executive officer of Vivace Therapeutics, said in the news release. "We are committed to continuing clinical development of VT3989 and discussing a move into a registrational phase 3 study in mesothelioma with FDA by the end of 2025."

VT3989 has shown encouraging clinical activity and a favorable safety profile in an ongoing open-label phase 1 study of more than 200 patients. Results have been especially notable in patients with mesothelioma whose cancer progressed after chemotherapy and immunotherapy, the only approved treatments for this disease. Additional findings will be presented at a major medical meeting in late 2025.

Results come from a phase 1 multi-center, open-label study that 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.

Trial Design

The phase 1 study of VT3989 included three parts. In the dose escalation phase, a traditional 3 + 3 design was used, which are tests a drug dose in groups of three patients, increasing the dose if side effects are limited, to assess safety in patients with metastatic solid tumors or mesothelioma 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 and schedule across up to six cohorts. These included patients with mesothelioma of any site (with or without NF2 mutations), non-pleural mesothelioma, pleural mesothelioma, and solid tumors with inactivating NF2 mutations or YAP/TAZ gene alterations.

In the combination phase, mesothelioma patients received VT3989 with the immunotherapy drugs Opdivo (nivolumab) and Yervoy (ipilimumab), while patients with non-small cell lung cancer and EGFR mutations received VT3989 with the targeted therapy osimertinib.

Patients were not eligible if they had active brain tumors or cancer that spread to the brain’s lining or if they had an ongoing infection requiring strong treatment. Those with HIV or active hepatitis B or C were also excluded. Patients with serious heart problems or certain irregular heartbeats were not eligible. Additional active cancers that could affect study results or pregnancy or breastfeeding also disqualified patients. Prior treatment with a TEAD inhibitor excluded patients except those with a rare cancer called epithelioid hemangioendothelioma.

Reference

1. “Vivace Therapeutics Announces Receipt of Orphan Drug Designation for VT3989 for Treatment of Mesothelioma,” Vivace Therapeutics. News Release. July 30th.

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