SUZHOU, China & ROCKVILLE, Md.—Ascentage Pharma recently announced that the U.S. Food and Drug Administration (FDA) has granted two Orphan Drug designations (ODDs) to two of the company’s apoptosis-targeting assets.
The first designation was granted to APG-115 for the treatment of acute myeloid leukemia (AML). APG-115 is a selective, small-molecule inhibitor of MDM2. It has strong binding affinity to MDM2, and is designed to activate the tumor-suppressing activity of p53 by blocking the MDM2-p53 protein-to-protein interaction. APG-115 is also reportedly the first MDM2-p53 inhibitor to enter clinical development in China, with multiple ongoing clinical studies in solid tumors and hematologic malignancies in China and the U.S.
AML is a highly heterogenous hematologic malignancy more common in the elderly population, with a median age of 68 at diagnosis. The most recent data from the Surveillance, Epidemiology, and End Results Program of the U.S. National Cancer Institute estimates that there will be 19,940 new cases of AML and an estimated 11,180 deaths from this disease in the U.S. in 2020. Despite the recent advances in therapeutics, the 5-year survival rate of AML remains at 25%–30%.
“AML and SCLC are both devastating and life-threatening diseases which have high unmet clinical needs globally. For APG-115, this designation marks the second ODD of the molecule from the FDA, while it is the very first time for APG-1252 to obtain an ODD,” said Dr. Yifan Zhai, chief medical officer of Ascentage Pharma. “All the ODD-related supporting policies in the US will help us to accelerate the global clinical development and commercialization of these two drug candidates, and allow more patients to benefit as soon as possible.”
The second Orphan Drug designation was granted to APG-1252 for the treatment of small-cell lung cancer (SCLC). APG-1252 is a novel small-molecule drug candidate that restores apoptosis by selectively inhibiting Bcl-2 and Bcl-xL proteins simultaneously. APG-1252 is currently being investigated in Phase 1 dose-escalation studies in patients with advanced cancers in the U.S. and Australia; a Phase 1b/2 study of APG-1252, plus paclitaxel, in patients with relapsed/refractory SCLC in the U.S.; and a Phase 1 dose-escalation study of APG-1252 in patients with SCLC in China.
13 to 15 percent of lung cancers are classified as SCLC, which is a rare and highly aggressive cancer with a low 5-year survival rate. Patients with relapsed/refractory SCLC have few treatment options, and those that exist offer modest response rates. The clinical data of APG-1252 generated so far have shown a favorable safety profile and preliminary efficacy in patients with SCLC and other advanced solid tumors.