Zanubrutinib sNDA for Marginal Zone Lymphoma Receives Priority Review Status

Recently, the FDA granted Priority Review status to a supplemental New Drug Application (sNDA) for zanubrutinib, MPR reports. While the treatment, under the brand name Brukinsa, is currently indicated for patients with mantle cell lymphoma, the sNDA is designed to mark zanubrutinib as a treatment for adult patients with previously treated marginal zone lymphoma. The sNDA, which makes changes to an existing and accepted NDA, hinges on data from the Phase 2 MAGNOLIA clinical trial.


Developed by BeiGene, zanubrutinib is a small molecule Bruton tyrosine kinase (BTK) inhibitor. As BeiGene explains:

BTK is a key component of the B-cell receptor, or BCR, signaling pathway and is an important regulator of cell proliferation and cell survival in various B cell malignancies. BTK inhibitors block BCR-induced BTK activation and its downstream signaling, leading to growth inhibition and cell death in certain malignant white blood cells called B-cells.

Zanubrutinib works by binding to BTK and inactivating the enzyme. Its efficacy comes from the inability to reverse this inactivation.

Within the clinical trial, researchers evaluated zanubrutinib for patients with marginal zone lymphoma who were previously treated with one or more anti-CD20-based therapies. Overall, 68 adult patients enrolled. 66 patients were evaluable. During the trial, patients received 160mg zanubrutinib 2x daily. The treatment is administered orally. Study findings showed:

  • Altogether, 74.2% of patients (49) responded to treatment. Of these, 16 patients achieved a complete response while the remainder achieved a partial response.
  • 80% of patients experienced no cancer progression within 6 months. Within 9 months, 67% of patients experienced no progression.
  • Overall, zanubrutinib was relatively safe and well-tolerated. However, some side effects did occur. These included fever, nausea, diarrhea or constipation, bruising, upper respiratory tract infections, thrombocytopenia (low platelet count), and neutropenia (low white blood cell count).

Altogether, the FDA hopes to respond to BeiGene about the approval decision by September 19, 2021.

Marginal Zone Lymphoma

Altogether, marginal zone lymphoma exists under the greater umbrella of non-Hodgkin’s lymphomas (NHLs). The cancer forms in white blood cells called lymphocytes within the mantle zone, a specific area within the lymph nodes. Doctors are not sure of the specific cause of this slow-growing cancer, though it has been associated with H. pylori infection and hepatitis C. Additional risk factors include age (60+), a history of autoimmune or inflammatory disorders, and being female.

Overall, there are three types of marginal zone lymphoma. First is extra nodal marginal zone B-cell lymphoma, which may also be known as mucosa-associated lymphoid tissue (MALT) lymphoma. This form is the most common and begins in the body outside of the lymph nodes. Next, nodal marginal zone B-cell lymphoma starts – and usually remains – within the lymph nodes. Finally, splenic marginal zone B-cell lymphoma usually forms in the bone marrow and spleen. This is the rarest form.

In early stages, many patients are asymptomatic. However, as the cancer progresses, symptoms include:

  • Persistent inflammation in affected areas
  • Nausea and vomiting
  • Extreme fatigue
  • Appetite loss
  • Fever
  • Unintended weight loss
  • Night sweats
  • Indigestion
  • Abdominal and/or chest pain
  • Heart burn
  • Bloating
  • Feeling of fullness
  • Spleen, liver, and tonsil enlargement

Learn more about marginal zone lymphoma here.

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.

Follow us