FDA Grants Orphan Drug Designation to APG-2575 for Treatment of Waldenström Macroglobulinemia

The FDA has granted an Orphan Drug designation to APG-2575 for the treatment of patients with Waldenström macroglobulinemia.

The FDA has granted an Orphan Drug designation to APG-2575 for the treatment of patients with Waldenström macroglobulinemia, according to a press release. This is the first Orphan Drug designation from the FDA granted for this BCL-2 inhibitor.

"Waldenström macroglobulinemia represents an unmet medical need globally,” said Dajun Yang, chairman and chief executive officer, Ascentage Pharmaceuticals, in a statement. “This Orphan Drug designation by the US FDA for the treatment of Waldenström macroglobulinemia marks an important milestone in the global development and commercialization of APG-2575.”

Patients with Waldenström macroglobulinemia are diagnosed at a median age of 70 years, and many patients are intolerant to the existing therapeutic options due to poor health conditions. Waldenström macroglobulinemia is a rare disease that makes up less than 2% of all cases of non-Hodgkin’s lymphoma in the United States. Overall, this patient population is in need of more effective and safe treatment options.

The National Comprehensive Cancer Network recommendations for treatment of patients with Waldenström macroglobulinemia suggest the current therapies have an objective response rate of around 80% but deliver a very low rate of very good partial responses or deep responses, around 20% or lower. Most patients also experience disease progression after the initial response.

APG-2575 is a novel agent administered orally. It is designed to treat a number of hematologic malignancies by blocking BCL-2 in order to restore normal apoptosis process in cancer cells. APG-2575 is 1 of few BCL-2 selective inhibitors that is currently available in clinical development worldwide. This is also the first BCL-2 inhibitor developed in China that has entered clinical trials.

The agent has received clearance and approvals for multiple studies, including phase 1B and 2 clinical trials. APG-2575 is under evaluation currently in the global multicenter phase 1B/2 clinical trial (NCT04260217) as a single agent or in combination with ibrutinib (Imbruvica)/rituximab (Rituxan) for the treatment of patients with Waldenström macroglobulinemia. The trial is designed to evaluate the safety, tolerability, and efficacy of this treatment.

This open-label study includes dose-escalation and dose-expansion phases, as well as multiple arms to subsequently add more treatment arms based on the clinical activity observed in the study. Two arms in the study initially include patients treated with APG-2575 as a single agent and patients treated with APG-2575 with ibrutinib.

The primary end points of the study include dose-limiting toxicity and maximum tolerated dose.

To be included in the study, patients must have a confirmed diagnosis of Waldenström macroglobulinemia with measurable disease. Patients in arm A should have received at least 1 prior line of therapy for Waldenström macroglobulinemia and have either failed or progressed while on or within 6 months of ibrutinib treatment or be intolerant to ibrutinib. Patients in arm B, which will treat patients with the combination of APG-2575 and ibrutinib, must have been previously untreated for Waldenström macroglobulinemia, while arm C could have received at least 1 prior line of therapy and have relapsed/refractory disease.

Patients must also have adequate hematologic, hepatic, and renal function, an ECOG performance status of ≤1, and a life expectancy of ≥3 months. Patients with central nervous system involvement, active infection, or any other serious unresolved medical conditions are unable to enroll to the study.


Ascentage Pharma's Bcl-2 Inhibitor APG-2575 Granted Orphan Drug Designation by the FDA for the Treatment of Waldenström Macroglobulinemia. News Release. July 15, 2020. Accessed July 15, 2020. https://prn.to/2CfmwSz