FDA Grants Orphan Drug Designation to HQP1351 in Chronic Myeloid Leukemia

There is a significant unmet clinical need [for] treatment of CML globally. This Orphan Drug Designation from FDA marks a major milestone for HQP1351..."

The FDA has granted Orphan Drug Designation to a third-generation BCR-ABL inhibitor, HQP1351, as treatment of patients with chronic myeloid leukemia (CML), according to a press release from Ascentage Pharma, developer of the agent.1

"There is a significant unmet clinical need [for] treatment of CML globally. This Orphan Drug Designation from FDA marks a major milestone for HQP1351 which will bring about the incentives and support that will enable us to further accelerate the global development and commercialization of this drug candidate," said Dr. Dajun Yang, chairman, and chief executive officer, Ascentage Pharma. "Given the favorable safety and efficacy data obtained thus far, we will expedite the development and are hopeful that HQP1351 will soon benefit patients worldwide."

At the close of 2019, updated data from a phase I study of HQP1351, conducted in China, were presented at the American Society of Hematology (ASH) Annual Meeting by the principal investigator, Qiam Jiang, MD of Peking University in China.2

In 101 patients with CML, the median follow-up duration was 12.8 months (range, 1.2-31.5 months).Of the patients enrolled, 87 were chronic phase (CP), and 14 were accelerated phase (AP). An 18-month progression-free survival (PFS) rate of 94% was achieved with HQP1351 in CP patients and 61% in AP patients. Anti-leukemic activity was also observed with the agent in patients with CML who were resistant to treatment with tyrosine kinase inhibitors (TKIs). The major cytogenetic response rate in patients with TKI-resistance was 82%, and the complete cytogenetic responses (CCyR) was 78%. Participants who received the agent for a longer duration had deeper responses. Specifically, the complete hematologic response rate for CP and AP were 95% and 85%, respectively.

Considering the absence of baseline CCyRs, treatment with the novel agent achieved CCyRs in 69% of patients with CP CML and 61% of those with AP CML. Of the individuals who were evaluable for major molecular response (MMR),the MMR rate was 37% in the CP group and 36% in the AP group.

The safety analysis showed that HQP1351is well-tolerated in patients with CML who are in either CP or AP. The drug was also tolerated at all 3-dose levels. The most common grade 3/4 treatment-related adverse event (TRAE) was thrombocytopenia, which occurred in 50% of patients. Grade 1/2 TRAEs were predominantly non-hematologic in nature.

The investigators noted that longer duration of treatment with HQP1351 led to a decrease in the incidence of all-grade TRAEs. There were no treatment-related deaths during the study.

Following a clearance by the FDA to conduct a phase Ib study in the United States, a multicenter, open-label, randomized trial was launched(NCT04260022) to investigate the pharmacokinetics of HQP1351. The study plans to accrue 30 patients with CML in CP, AP of any phenotype, and with or without T315l mutation.1

Patients will be randomized 1:1:1 to receive a 30 mg, 40 mg, 50 mg dose of HQP1351 orally, every other day. The co-primary end points of the trial are the maximum plasma concentration of HQP1351 and the area of the curve of HQP1351.

The study is actively recruiting patients who meet the eligibility criteria, which include an ECOG performance status of 2 or lower, a minimum life expectancy of at least 3 months, and adequate organ function.


1. Ascentage Pharma's core drug candidate HQP1351 granted Orphan Drug Designation by the US FDA for the treatment of patients with chronic myeloid leukemia [news release]. Suzhou, China and Rockville, MD: Ascentage Pharma; May 4, 2020. https://prn.to/2L0Z1h2. Accessed May 4, 2020.

2. Ascentage Pharma releases updated data of its novel BCR-ABL inhibitor, HQP1351, in an oral presentation nominated for "Best of ASH" [new release]. Suzhou, China and Rockville, MD: Ascentage Pharma December 10, 2020. https://prn.to/2YKd9U7. Accessed May 4, 2020.