FDA Grants Breakthrough Therapy Designation to Pimicotinib for TGCT


Based on results from a phase 1b study of pimicotinib showing the therapys efficacy in patients with tenosynovial giant cell tumor, the agent has gained breakthrough therapy designation from the FDA.

The FDA granted breakthrough therapy designation to the CSF-1R inhibitor, pimicotinib (ABSK02), for the treatment of patients with tenosynovial giant cell tumor (TGCT) who are not amenable to surgery.1

The basis of this breakthrough therapy designation comes from findings of the TGCT cohort of an open-label phase 1b clinical trial (NCT04192344) evaluating pimicotinib.

Pimicotinib is a novel small molecule inhibitor of CSF-1R, which is orally available, highly selective, and highly potent. The agent is being investigated for use in patients with TGCT, who have chronic graft-versus-host disease, and is also being examined as a potential treatment option across additional cancer types.

According to the drug developer Abbisko Therapeutics, pimicotinib is the first new-generation CSF-1R inhibitor to gain this designation.

"We are very pleased to learn that the FDA has granted pimicotinib the breakthrough therapy designation. The granting of this designation also marks an essential step in the [research and development] and innovation of Abbisko Therapeutics in going global," said Xu Yao-Chang, MD, chairman and chief executive officer of Abbisko Therapeutics, in a press release. "Pimicotinib's [United States] breakthrough therapy designation shows FDA's recognition of pimicotinib's early data and affirmation of the company's [research and development] strength. It will make our clinical development process and finished drug progress more efficient, which will help shorten the time to market and benefit patients worldwide as soon as possible."

Pimicotinib was previously granted a breakthrough therapy designation in China from the Center for Drug Evaluation of the National Medical Products Administration for this patient population in July 2022. Following this designation, a phase 3 clinical trial gained approval to allow for the evaluation of pimicotinib in patients with TGCT in October 2022.

In the TGCT cohort of an open-label phase 1b clinical trial, investigators sought to evaluate pimicotinib to assess its safety, tolerability, and pharmacokinetics (PK) in patients with advanced solid tumors.

Inclusion in this trial was open to patients with confirmed solid tumors that have progressed on, are intolerant to standard therapy, or for whom no standard therapy exists. Patients must have an ECOG performance status of 0-1, a life expectancy of 3 months or more, and adequate bone marrow and organ function.

During the study, patients were given a starting dose of 25 mg oral pimicotinib once a day using a 3+3 dose-escalation style. Then, patients were administered a single dose of pimicotinib on day -3, followed by 3 days off as a run-in period in order to determine the safety and PK of the treatment at a single dose. Patients continued to receive pimicotinib once a day in repeated 28-day cycles.2

The primary end points of the study were to determine the dose limiting toxicities, incidence, and severity of adverse events (AEs). Secondary end points included progression-free survival, duration or response, disease control rate, PK, bioavailability, and elimination half-life.

Preliminary findings from the trial were presented at the CTOS 2022 Annual Meeting. Here, a total of 20 patients were eligible for evaluation following treatment for TGCT in China, and results revealed that 74% continued to receive treatment for at least 3 months.3

Among patients, the overall median duration of treatment was 105 days (range, 49-164). The overall response rate at week 13 was 35% (95% CI, 15.4%-59.2%), and for preliminary PK results, pimicotinib demonstrated to have a quick absorption and relatively long elimination. This finding supports daily dosing of the agent.

Moreover, treatment notable pharmacodynamic marker changes were observed in the trial, including induction of CSF1 and reduction of non-classical monocytes and C-terminal telopeptide. Regarding safety, most treatment-emergent AEs were deemed grade 1 or 2.

Abbisko therapeutics announces that US FDA has granted breakthrough therapy designation for its CSF-1R inhibitor pimicotinib(ABSK021). News release. Abbisko Therapeutics Co., Ltd. January 29, 2023. Accessed January 31, 2023. https://yhoo.it/40tIIPt
A study to assess the safety, tolerability, and pharmacokinetics of ABSK-021 in patients with advanced solid tumor. Clinicaltrials.gov. December 10, 2019. Accessed January 30, 2023. https://bit.ly/3Y8qmRX
Xu H, Li B, Luo Y, et al. Preliminary phase 1b results of ABSK021 for advanced tenosynovial giant cell tumor: significant antitumor activity and favourable safety profile. Presented at CTOS 2022 Annual Meeting; November 16-19, 2022; Vancouver, BC. Abst P164.
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