FDA Grants Orphan Drug Designation for Ocifisertib to Treat Patients With AML


Currently, ocifisertib is being evaluated in a phase 1b and 2 trial to confirm the safety and tolerability profiles in patients with acute myeloid leukemia.

The FDA has granted an orphan drug designation to ocifisertib (CFI-400945; Treadwell Therapeutics) for the treatment of acute myeloid leukemia (AML). Orphan drug designations are granted by the FDA to drugs that are intended for the treatment, prevention, or diagnosis of a rare disease or condition that affects less than 200,000 people in the US at the time of the designation.1

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Image credit: wladimir1804 | stock.adobe.com

Ocifisertib is a first-in-class, investigational PLK4 inhibitor for the treatment of AML that regulates centriole duplication in patients. In a previous phase 1 clinical trial, the investigators established a safety and tolerability of ocifisertib in patients with advanced solid tumors.2

Continuous daily oral dosing of ocifisertib was evaluated by the incidence of dose-limiting toxicities (DLTs) during the first 28-day treatment cycle. A total of 43 patients were treated in dose escalation (increasing from 3 mg to 96 mg per day), whereas 9 patients were treated in a 64 mg-dose expansion. The results indicated that ocifisertib was well-tolerated at 64 mg-doses for patients with dose-dependent neutropenia. After DLT occurred at both 96 mg and 72 mg doses, 64 mg was established as the recommended phase 2 dose.2

“The FDA’s decision to grant orphan drug designation, along with the previous FDA Fast Track designation for ocifisertib, underscores [our] dedication to addressing this patient population with few treatment options. Patients with relapsed and/or refractory AML—in particular TP53-mutated disease—suffer poor overall survival and represents a high unmet clinical need,” said Roger Sidhu, MD, acting CEO of Treadwell Therapeutics, in a press release.1

Currently, the drug’s previously determined safety, efficacy, pharmacokinetics, and pharmacodynamics are being confirmed in adults with relapsed or refractory AML following standard of care therapy in a phase 1b and 2 trial. In addition, the ongoing study also examines individuals with myelodysplastic syndrome and chronic myelomonocytic leukemia. The safety and tolerability profiles of ocifisertib are being examined both alone and in combination with azacitidine.1,3

In the phase 1 trial, the most common (>5%) treatment-related adverse events (AEs) were fatigue (37%), nausea (29%), diarrhea (21%), neutropenia (21%), anorexia (19%), vomiting (8%), dyspepsia (6%), hypomagnesemia (6%), and dehydration (6%). According to the investigators, these were low-grade and demonstrated no clear dose-dependent trends, except for neutropenia. Further, most grade 3 to 4 neutropenic AEs (60%) had occurred during cycle 1 with a median time to first event occurring at 18 days. In addition, a total of 27 patients (52%) had dose interruptions and 3 (6%) were dose reduced at the 72 mg (1 patient reduced to 48 mg) and 96 mg (2 patients reduced to 72 mg) dose levels due to recurrent neutropenia.2

“We look forward to advancing ocifisertib in partnership with investigators, regulators, patients and their families for those with limited treatment options in tough to treat AML,” said Sidhu in the press release.1


  1. Treadwell Therapeutics. Treadwell Announces Ocifisertib, a First-in-Class PLK4 Inhibitor, has Received Orphan Designation from U.S. FDA for the Treatment of Acute Myeloid Leukemia. News release. February 20, 2024. Accessed February 21, 2024. https://www.businesswire.com/news/home/20240220180549/en
  2. Veitch, Z.W., Cescon, D.W., Denny, T. et al. Safety and tolerability of CFI-400945, a first-in-class, selective PLK4 inhibitor in advanced solid tumours: a phase 1 dose-escalation trial. Br J Cancer 121, 318–324 (2019). doi:10.1038/s41416-019-0517-3
  3. A Study of CFI-400945 Fumarate in Patients With Advanced Cancer. ClinicalTrials.gov identifier: NCT01954316. Updated January 17, 2024. Accessed February 21, 2024. https://clinicaltrials.gov/study/NCT01954316
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