FDA Grants Orphan Drug Designation to EP0042 for AML

The FDA has granted orphan drug designation to the investigational dual FLT-3 and Aurora kinase inhibitor EP0042 for the treatment of pretreated acute myeloid leukemia (AML), according to a press release from Ellipses Pharma.¹

"The designation is an important milestone in the development of EP0042 and underscores the work we are already undertaking towards accelerating its potential access to patients," according to the manufacturers of EP0042.

The designation followed data from a phase 1/2 trial (NCT04581512) that was presented at the 2022 American Society of Hematology (ASH) Annual Meeting. At the meeting, preliminary data indicated that EP0042 was safe and tolerable as monotherapy and provided evidence of prolonged disease control in pretreated patients with AML. The FDA originally accepted an investigational new drug application for EP0042 in February 2023.

“The designation is an important milestone in the development of EP0042 and underscores the work we are already undertaking towards accelerating its potential access to patients,” Rajan Jethwa, MA, MRCS, chief executive officer and co-founder of Ellipses, said in the press release. “We believe its early clinical data merits its continued study, and this FDA decision further focuses our vision as we continue our drive towards bringing EP0042 to more patients.”

The data read out at ASH indicated that no dose-limiting toxicities associated with EP0042 were identified.² Of 25 patients across 6 dosing cohorts, patients had a median number of 2 (range, 1-6) prior lines of therapy, with some receiving a prior FLT3 inhibitor. Additionally, common adverse effects included febrile neutropenia, fatigue, diarrhea, peripheral edema, and dizziness.

EP0042’s dual inhibition of FLT3 and Aurora kinase has previously demonstrated the ability to overcome FLT3 inhibition resistance in both in-vitro and in-vivo clinical models.

In the multi-part, open-label, modular phase 1/2 trial, investigators evaluated the safety and tolerability of EP0042 in pretreated patients with AML. In the trial, patients received EP0042 orally in 20 mg to 50 mg capsules.

The primary end point of the trial was incidence of dose-limiting toxicities for up to the first cycle of treatment or 28 days.

Patients 18 years and older with pathologically documented AML were eligible for enrollment on the trial. Additional inclusion criteria included having the ability to swallow and retain oral medication, sufficient life expectancy to complete at least 1 cycle or 28 days of treatment, and an ECOG performance status of 0 to 2 at screening.

Patients with suspected brain or leptomeningeal metastases or acute promyelocytic leukemia were not eligible for enrollment on the trial. Patients were also unsuitable for enrollment if they had received systemic anti-cancer therapy within 4 weeks of beginning study treatment, underwent autologous or allogeneic transplantation within 90 days of study initiation, had inadequate liver function, any severe cardiac or respiratory conditions that could jeopardize patient safety during treatment, or any malignant disease or other than AML.

“We are excited to continue the positive momentum in the clinical development of this drug, including progressing the ongoing phase 1/2 trial following the [investigational new drug application] received earlier this year,” Tobias Arkenau, global head of drug development and chief medical officer of Ellipses, concluded.

References

1. Ellipses Pharma: EP0042 receives orphan drug designation from the US Food and Drug Administration. News release. Ellipses Pharma. March 14, 2023. Accessed March 15, 2023. bit.ly/3TfwRRN
2. Ellipses Pharma presents preliminary data from the first in human phase-1/2 trial of EP0042, a dual FLT-3 and Aurora kinase inhibitor, at ASH. News release. Ellipses Pharma. December 12, 2022. Accessed March 15, 2023. http://bit.ly/3yG9GGL