Ascentage Pharma announced the US Food and Drug Administration (FDA) has granted two Orphan Drug Designations (ODDs) to two of the company's apoptosis-targeting assets: the MDM2-p53 inhibitor, APG-115, for the treatment of acute myeloid leukemia (AML); and the Bcl-2/Bcl-xL inhibitor, APG-1252, for the treatment of small-cell lung cancer (SCLC). With these two latest designations, Ascentage Pharma has obtained a total of six ODDs from the FDA for four of the company's investigational drug candidates.

The term "orphan drugs" refers to pharmaceutical products developed for the prevention, diagnosis, and treatment of rare diseases or conditions. In the United States, an orphan disease is defined as a disease or condition with a prevalence of less than 200,000 patients in the country. Since the Orphan Drug Act was passed in 1983, the US government has provided incentives and policy support to encourage development of orphan drugs. Drug candidate granted ODDs by the FDA will qualify for various development incentives, including a tax credit on expenditures incurred in clinical studies, a waiver of the New Drug Application (NDA) fee, research grant awarded by the FDA, and seven years of US market exclusivity upon approval.

AML is a highly heterogenous hematologic malignancy that is more common in the elderly population with a median age at diagnosis of 68 years. The most recent data from the Surveillance, Epidemiology, and End Results Program (SEER) of the US National Cancer Institute (NCI) estimates that there will be 19,940 new cases of AML and an estimated 11,180 deaths from this disease in the United States in 2020. Despite the recent advances in therapeutics, the 5-year survival rate of AML remains at 25%–30%, which still represents a significant unmet medical need.

APG-115 is an orally administered, selective, small-molecule inhibitor of MDM2. APG-115 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 (PPI). APG-115 is the first MDM2-p53 inhibitor entering clinical development in China, with multiple ongoing clinical studies in solid tumors and hematologic malignancies in China and the US.

Lung cancer remains the leading cause of cancer death in the United States. Lung cancer is divided into two main histopathological types: non-small cell lung cancer (NSCLC) and SCLC, with 13-15% of lung cancers classified as SCLC. SCLC is a rare and highly aggressive cancer with a low 5-year survival rate. Patients with relapsed/refractory SCLC have few treatment options, all of which offer modest response rates.

Being developed by Ascentage Pharma, 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 I dose-escalation studies in patients with advanced cancers in the US and Australia, a Phase Ib/2 study of APG-1252 plus paclitaxel in patients with relapsed/refractory SCLC in the US, and a Phase I dose-escalation study of APG-1252 single agent in patients with SCLC in China. The clinical data of APG-1252 generated thus far have shown a favorable safety profile and preliminary efficacy in patients with SCLC and other advanced solid tumors.

"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."