FDA Grants Orphan Drug Designation to PCLX-001 for AML

The FDA has granted an orphan drug designation (ODD) to PCLX-001 (DDD86481) for the treatment of patients with acute myeloid leukemia (AML).¹

PCLX-001 is a first-in-class N-myristoylation (NMT) inhibitor that is currently being studied in non-Hodgkin lymphoma (NHL) and solid tumors at 4 sites in Canada as part of a phase 1 trial (NCT04836195). An investigational new drug application has also been filed to study PCLX-001 in patients with AML in the United States.

“The 5-year survival rate for AML patients 20 and older is only 27%. Patients relapse despite existing therapies. We are developing a first-in-class therapy that tackles AML in a new way that has been very effective in disease models and may be synergistic with other approaches,” Michael Weickert, PhD, president and chief executive officer of Pacylex, stated in a press release. “Our trial will offer relapsed patients another option. This ODD for PCLX-001 recognizes the importance of this potential new therapy for these patients.”

Preclinical models showed that PCLX-001 monotherapy generated complete remissions in subcutaneous AML cell line–derived xenografts. Additionally, PCLX-001 elicited up to 95% reduction of human peripheral blood and bone marrow CD45+ cells, which include the malignant stem cell population responsible for disease relapse, in tail vein–injected, AML patient–derived xenografts.

The planned study evaluating PCLX-001 in patients with AML will be the first to examine an NMT inhibitor as a treatment for the disease.

The ongoing phase 1 trial is investigating PCLX-001 monotherapy in patients with histologically confirmed advanced solid tumors who have failed at least one prior therapy and/or are not eligible for therapies expected to provide clinical benefit, or histologically confirmed B-cell lymphomas that are expected to express CD20, including diffuse large B-cell lymphoma, high grade B-cell lymphoma, follicular lymphoma (grades I to IIIB), mantle cell lymphoma, and Burkitt lymphoma who have failed at least two prior therapies and/or are not eligible for therapies expected to provide clinical benefit (including autologous stem cell transplantation).²

The trial is comprised of two parts, including single-agent dose escalation in part A and single-agent expansion cohorts in part B. In part A, the trial will follow a 3+3 design. If no dose-limiting toxicities are observed in 3 patients at a dose level, 3 more patients will be treated at the next dose level. Patients will receive oral PCLX-001 daily as part of a 28-day cycle, and the starting dose of PCLX-001 will be 20 mg daily. After the maximum tolerated dose (MTD) is defined in part A, patients in part B will receive the MTD.

“Our ongoing clinical trial in [patients] with NHL and solid tumors showed PCLX-001 was well-tolerated and achieved drug exposures likely to benefit [patients with] AML,” John Mackey, MD, chief medical officer of Pacylex, stated in a press release. “We look forward to treating AML patients with PCLX-001 in the near future.”

References

1. Pacylex announces orphan drug designation granted to PCLX-001 for the treatment of acute myeloid leukemia. News release. Pacylex. October 14, 2022. Accessed October 17, 2022. https://bit.ly/3MBqK70
2. Phase I trial of PCLX-001 in B-cell non-Hodgkin lymphoma and advanced solid malignancies. ClinicalTrials.gov. Updated September 27, 2022. Accessed October 17, 2022. https://clinicaltrials.gov/ct2/show/NCT04836195