Orelabrutinib for MCL Granted Breakthrough Therapy Status

According to the Cancer Network, orelabrutinib, a Bruton tyrosine kinase (BTK) inhibitor, was recently granted Breakthrough Therapy designation within the United States. While the treatment is also indicated for patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL), the Breakthrough Therapy designation was granted for patients with R/R mantle cell lymphoma (MCL).


Developed by InnoCare Pharma Ltd. (“InnoCare”), orelabrutinib is described as:

an orally available potent BTK inhibitor that irreversibly binds to BTK to induce downstream kinase activation and cell death. Orelabrutinib was designed with a single ring at the scaffold center instead of a fused bi-cycle core [to convey] higher selectivity…which should result in fewer off-target side effects.

The Breakthrough Therapy designation was granted based on data from a Phase 2 clinical trial evaluating orelabrutinib for patients with MCL. Altogether, 106 patients enrolled. Within the follow-up period, 87.9% (93 patients) achieved an objective response, though response duration and progression-free survival endpoints were not achieved. While the treatment was relatively safe and well-tolerated, side effects included leukopenia (low leukocyte levels), neutropenia (low neutrophil levels), thrombocytopenia (low platelet count), and high blood pressure.

Breakthrough Therapy designation is granted to expedite the development and review of drugs and biologics intended to treat serious or life-threatening conditions. To receive this status, the drug must also show improvement or efficacy over currently available treatment options. Outside of Breakthrough Therapy designation, Orelabrutinib has also received Orphan Drug designation from the FDA.

Mantle Cell Lymphoma (MCL)

As a form of non-Hodgkin’s lymphoma (NHL), mantle cell lymphoma (MCL) affects the lymphatic system. In particular, MCL arises from cancerous B cells (a type of white blood cell) within the mantle zone. There is no known cause for MCL. However, the cancer has been linked to the over-release of cyclin D1 protein, prompting uncontrolled B cell growth. In early stages, many patients are asymptomatic (have no symptoms). However, as the condition progresses, symptoms include:

  • Nausea and vomiting
  • Painless but swollen lymph nodes, usually in the neck, throat, elbows, shoulders, or chest
  • Appetite loss
  • Unintended weight loss
  • Fever
  • Diarrhea
  • Lower back pain/pressure
  • Enlarged tonsils, liver, and/or spleen
  • Feeling of “fullness”
  • Indigestion, heartburn, or bloating
  • Headache (if it spreads to the spinal cord)
  • Loss of balance and coordination (if spread)
Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

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