Ascentage Pharma announced that the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA) has recommended the novel candidate drug olverembatinib (HQP1351) of Guangzhou Healthquest Pharma, a wholly-owned subsidiary of Ascentage Pharma, for a Breakthrough Therapy Designation (BTD) for the treatment of patients with chronic-phase chronic myeloid leukemia (CP CML) resistant and/or intolerant to first- and second-generation tyrosine kinase inhibitors (TKIs).
This BTD recommendation marks another major development for olverembatinib following the Priority Review granted by the CDE in October 2020. The indication of BTD recommendation is an expansion from that of the Priority Review designation.
According to the NMPA's Provisions for Drug Registration (SAMR Order No. 27) and Working Procedures for Review of Breakthrough Therapeutics implemented on July 1, 2020, the breakthrough therapy review policy is designed to promote the research and creation of drugs with apparent clinical advantages, which are intended for the prevention or treatment of serious life-threatening diseases or diseases which severely impact the quality of life for which there is no existing treatment or where sufficient evidence indicates advantages of the novel drug over currently available treatment options. Drugs that have been granted the BTD are prioritized by the CDE in communications and exchange, and in receiving guidance to promote the drug development progress. Furthermore, BTD designated drugs will be eligible to the Priority Review status that will accelerate the review process at the stage of application for commercialization. In conclusion, this measure will effectively accelerate the development and review of drugs presenting significant clinical value or addressing urgent clinical needs.
CML is a hematologic malignancy of the white blood cells. Following the commercialization of BCR-ABL TKIs, the treatment of CML has been revamped. However, despite clinical benefits offered by the first-generation BCR-ABL inhibitor imatinib (gleevec), and several second-generation TKIs, acquired resistance to TKIs remains a major challenge in the treatment of CML. BCR-ABL tyrosine kinase mutations represent a key mechanism of acquired drug resistance; T315I, which is the most common drug-resistant mutation, occurs in about 25% of patients with drug-resistant CML. Patients with T315I-mutant CML are resistant to both first- and second-generation BCR-ABL inhibitors, presenting an urgent unmet medical need for an effective new generation treatment.
Olverembatinib is a novel, orally active, potent third-generation BCR-ABL inhibitor designed to effectively target BCR-ABL mutants, including T315I, and the first China-developed third-generation BCR-ABL inhibitor targeting drug-resistant CML. In July 2019, olverembatinib was cleared by the US Food and Drug Administration (FDA) to enter a phase Ib clinical study. In May 2020, olverembatinib was granted an Orphan Drug Designation and a Fast Track Designation by the FDA.
“Acquired drug resistance to TKIs remains an urgent unmet medical need and a major challenge in the treatment of CML,” commented Professor Xiaojun Huang, director of the Institute of Hematology, Peking University, and the principal investigator of olverembatinib in China. “Currently, no third-generation TKI has been approved in China, and no TKIs approved overseas is expected to enter China anytime soon. Multiple studies of olverembatinib, a China-developed BCR-ABL TKI, have consistently demonstrated promising efficacy and favorable safety in patients with drug-resistant CML, signifying significant potential clinical benefit to the patient population. We hope this BDT will further accelerate the clinical development and the review process for olverembatinib, and ultimately allow patients to soon benefit from this novel therapeutic.”
“Olverembatinib is our first candidate drug entering the NDA-stage, and it is expected to become the first approved third-generation BCR-ABL inhibitor in China,” said Dr. Yifan Zhai, chief medical officer of Ascentage Pharma. “This BTD for olverembatinib for the treatment of patients with CP CML intolerant or resistant to first- and second-generation TKIs represents the strong recognition of olverembatinib's therapeutic potential in addressing the unmet medical needs in the treatment of CML. Being granted this BTD will strengthen our communication with the CDE, and more importantly, pave the way for a Priority Review designation to the future NDA for this indication, thus accelerate the clinical development and the approval of olverembatinib in China, and help us to make olverembatinib available to patients as early as possible.”