FDA Grants Fast Track Designation to LSD1 Inhibitor SP-2577 for Ewing Sarcoma

SP-2577 (Seclidemstat), a potent reversible LSD1 inhibitor, has been granted Fast Track Designation by the FDA for the treatment of relapsed/refractory patients with Ewing sarcoma, Salarius Pharmaceuticals, Inc. developers of the drug, announced in a press release.

The agent is currently under investigation in an ongoing phase I trial (NCT03600649) in patients with Ewing sarcoma. The open-label, non-randomized study aims to find a dose of SP-2577 using an accelerated dose-escalation followed by a conventional 3+3 dose escalation phase to reach the maximum tolerated dose. Investigators aim to enroll 50 patients on trial, with enrollment closing in April 2020.

“Securing FDA Fast Track Designation for Seclidemstat in Ewing sarcoma is an achievement for Salarius in the ongoing development of the drug and recognition that there is an unmet need to bring much needed hope to patients and their families suffering through this devastating disease,” said David Arthur, president and chief executive officer of Salarius, in a statement. “Coupled with Seclidemstat’s previously granted Orphan Drug Designation and Rare Pediatric Disease Designation by the U.S. Food and Drug Administration, we feel well positioned to take advantage of the FDA’s expedited programs for drug development and review.”

SP-2577 is a first-in-class oral, small molecule that is designed for the reversible inhibition of LSD1. SP-2577 could offer more efficacy to patients with Ewing sarcoma, as well as more flexible dosing and fewer toxicities.

In the trial, patients receive SP-2577 orally twice daily. The primary end point of the trial is to define the safety and tolerability of the LSD1 inhibitor, assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Secondary end points include identification of a maximum tolerated dose, characterization of the pharmacokinetics, and efficacy, in terms of overall response rate, duration of response, and progression-free survival.

To be included in the study, patients must have a histologically confirmed diagnosis of Ewing sarcoma that is relapsed/refractory with at least 1 prior treatment. Patients must be at least 12 years or older, as well as Karnofsky ≥70% for over ≥16 years old and Lansky ≥70% for under 16 years old. Their ECOG performance status should be either grades 0 or 1, and their life expectancy should be greater than 4 months, among other inclusion criteria.

Patients who have not recovered to grade 2 or baseline from adverse events from previous therapies and patients who are receiving any other investigational agents are unable to be included in the study. Additionally, those with a prior LSD1 targeted therapy, systemic anti-cancer therapy, immunotherapy, palliative radiotherapy, or long-acting myeloid growth factor within a certain amount of time cannot be included on trial, among other exclusion criteria.

“Ewing sarcoma is a rare and deadly bone cancer that most often strikes children and young adults and for which there are no targeted therapies approved. SP-2577 has demonstrated a potential to address this considerable unmet need, and we look forward to rapidly advancing its development so that it soon may be available to those patients most in need,” said Damon Reed, MD, director of the Adolescent and Young Adult Program at the Moffitt Cancer Center andprincipalinvestigator of the Salarius Ewing sarcoma clinical trial, in a statement.

The Fast Track Designation is designed to expedite the process of developing and reviewing drugs that have the potential to treat serious or life-threatening conditions, ultimately helping to fulfill unmet medical needs. The FDA’s goal with this designation is to streamline the regulatory submissions. The FDA also frequently communicates questions or concerns on the drug to assure that any issues are resolved quickly during the review process. The ultimate goal is to get select drugs to market quicker to better treat patients.

Reference:

Salarius Pharmaceuticals Receives FDA Fast Track Designation for Lead Drug Candidate, Seclidemstat, in Relapsed or Refractory Ewing Sarcoma. Global Newswire website.https://bit.ly/2LZ3AcD. Published December 16, 2019. Accessed December 17, 2019.