FDA Grants Breakthrough Designation to Mantle Cell Lymphoma Drug


Orelabrutinib is a highly selective Bruton's tyrosine kinase inhibitor designed to target B-cell lymphomas and autoimmune indications.

The FDA has awarded breakthrough therapy designation to orelabrutinib (ICP-022) for the treatment of relapsed/refractory mantle cell lymphoma (MCL).1

Orelabrutinib is a highly selective Bruton's tyrosine kinase (BTK) inhibitor designed to target B-cell lymphomas and autoimmune indications. It was developed to have more effective target selectivity compared with ibrutinib (Imbruvica) and acalabrutinib (Calquence), which should also improve safety.

“We are very proud that orelabrutinib was granted breakthrough therapy designation after obtaining orphan drug designation,” said Jasmine Cui, PhD, cofounder, chairwoman, and chief executive officer of InnoCare Pharma, in a press release. “We will continue to uphold the concept of ‘science drives innovation for the benefit of patients’ and accelerate clinical trials for multiple indications of orelabrutinib in China and the rest of the world to benefit patients worldwide.”

An open-label, multicenter, phase 2 trial, evaluated the safety, tolerability, and efficacy of orelabrutinib, following oral administration, in Chinese patients with relapsed/refractory chronic lymphocytic leukemia (CLL)/small cell leukemia (SLL).2

The primary end point was objective response rate (ORR), with key secondary end points including duration of response (DOR), progression-free survival (PFS), and safety. Response was evaluated in accordance with 2008 International Workshop on Chronic Lymphocytic Leukemia criteria with modification for partial response (PR) with lymphocytosis (PR-L).

Eighty patients with relapsed/refractory CLL were enrolled to the trial, of whom 70 had CLL and 10 had SLL. At a data cutoff of May 31, 2019, half of the patients (n = 40) completed 6 cycles of treatment.

At a median follow-up of 6.3 months (range, 0.4-13.7), 78 patients were found to be evaluable for response. Orelabrutinib was found to have an ORR of 88.5% (n = 69), with 1 patient achieving a complete response, 39 achieving PR, and 29 with a PR-L.

Further, 7.7% of patients experienced disease stability. The median DOR had not yet been reached, and the 6-month DOR rate was 89.8%. The disease control rate achieved with the BTK inhibitor was 96.2%.

The most common adverse effects (AEs) of any cause were hematologic toxicities that were well characterized, including thrombocytopenia, neutropenia, and anemia.

Patients also reported respiratory system infections and purpura. However, there were no patients who experienced atrial fibrillation or secondary malignancy. The most common any-grade grade 3 or higher AEs comprised neutropenia, thrombocytopenia, and lung infections.

A total of 25 patients reported at least 1 serious toxicity with the BTK inhibitor, 13 of which were found to be associated with the agent and included decreased platelet count (n = 3), pneumonitis (n = 2), pyrexia (n = 2), and herpes zoster (n = 1).

In December 2020, the China’s National Medical Products Administration (NMPA) approved the agent for use in the following indications: patients with relapsed/refractory CLL/SLL and those with relapsed/refractory MCL.


  1. InnoCare announces breakthrough therapy designation of orelabrutinib by US FDA for treatment of R/R MCL. News release. InnoCare Pharma. June 28, 2021. Accessed June 29, 2021. https://prn.to/35VpN4Z
  2. Xu W, Song Y, Li Z, et al. Safety, tolerability and efficacy of orelabrutinib, once a day, to treat Chinese patients with relapsed or refractory chronic lymphocytic leukemia/small cell leukemia. Blood. 2019;134(suppl 1):4319. doi:10.1182/blood-2019-123331.
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