FDA Grants HQP1351 Orphan Drug Status in CML

The FDA has granted an orphan drug designation to HQP1351 for the treatment of patients with chronic myeloid leukemia.

The FDA has granted an orphan drug designation to HQP1351 for the treatment of patients with chronic myeloid leukemia (CML), according to Ascentage Pharma, the developer of the third-generation BCR-ABL inhibitor.1

Data were presented at the 2019 ASH Annual meeting from a phase 1 trial of HQP1351 in Chinese patients with TKI-resistant CML in the chronic phase (CP) or accelerated phase (AP).2 Among evaluable patients, the complete hematologic response rate was 95% in CP and 85% in AP.

The orphan designation will facilitate the review and development of HQP1351 in this setting. In a press release, Ascentage reported that there is an ongoing pivotal phase 2 study of HQP1351 in China.

"There is significant unmet clinical need in the treatment of CML globally. This orphan drug designation from the 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," Dajun Yang, MD, PhD, chairman and CEO of Ascentage, stated in the press release. "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."

In the phase 1 trial, HQP1351 was administered once every other day in 28-day cycles at 1 of 11 doses ranging from 1 mg to 60 mg. Overall, 101 patients were enrolled as of May 27, 2019, including 87 CP patients and 14 AP patients. It was determined that the dose-limiting dose was 60 mg, the maximum-tolerated dose was 50 mg, and the recommended phase 2 dose was 40 mg.

The median follow-up was 12.8 months (range, 1.2-31.5), and the 18-month progression-free survival rate was 94% in CP patients and 61% in AP patients. Among evaluable patients, the major molecular response rate was 37% in CP patients and 36% in AP patients.

Of the 95 evaluable patients who at baseline had a non-complete cytogenetic response (CCyR), 69% of the CP patients reached a major cytogenetic response (MCyR), including 61% who achieved a complete cytogenetic response (CCyR). Further, 43% of the AP patients reached an MCyR, of whom 36% had a CCyR.

Also of note, the BCR-ABL inhibitor demonstrated strong activity in patients with TKI-resistant disease with the T315I mutation. In CP patients in this subgroup, the MCyR rate was 82%, and the CCyR rate was 78%.

The treatment was well tolerated overall. The majority of nonhematologic treatment-related adverse events (TRAEs) were grade 1 or 2. Thrombocytopenia (50%) was the most frequent grade 3/4 hematologic TRAE. The overall occurrence of TRAEs went down as the duration of treatment increased, and there were no treatment-related deaths.


  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. Published May 4, 2020. https://prn.to/2zQC8dI. Accessed May 4, 2020.
  2. Jiang Q, Huang X, Chen Z, et al. An updated safety and efficacy results of phase 1 study of HQP1351, a novel 3rd generation of BCR-ABL tyrosine kinase inhibitor (TKI), in patients with TKI resistant chronic myeloid leukemia. Blood. 2019;134(suppl 1; abstr 493). doi: 10.1182/blood-2019-124295.