Brukinsa (zanubrutinib) to Treat Waldenstrom’s Macroglobulinaemia, USA
Join Our Newsletter - Get important industry news and analysis sent to your inbox – sign up to our e-Newsletter here

Brukinsa (zanubrutinib) for the Treatment of Waldenstrom’s Macroglobulinaemia

Brukinsa® is indicated to treat Waldenstrom’s macroglobulinemia (WM) and mantle cell lymphoma (MCL) in adult patients.

Drug Name

Brukinsa® (zanubrutinib)



Therapy Class

Bruton’s tyrosine kinase inhibitor

Current Indication

Waldenstrom’s macroglobulinaemia and mantle cell lymphoma


Brukinsa® (zanubrutinib) is a highly selective Bruton’s tyrosine kinase (BTK) inhibitor indicated for the treatment of Waldenstrom’s macroglobulinaemia (WM) and mantle cell lymphoma (MCL) in adults.

Developed by Chinese biopharmaceutical company BeiGene, Brukinsa is available as an 80mg white to off-white opaque capsule for oral administration. Its recommended dosage is 160mg twice daily or 320mg once daily, administered either with or without food.

Regulatory approvals for Brukinsa

Brukinsa was first approved by the US Food and Drug Administration (FDA) in November 2019 for the treatment of MCL in adult patients who had received at least one prior regimen. In the same month, US-based pharmaceutical technology company Catalent entered a long-term agreement with BeiGene for the production and commercial supply of the drug.

In June 2020, Brukinsa was accepted by the European Medicines Agency (EMA) for regulatory review for the treatment of WM in patients who had received at least one prior therapy, or for treatment-naive patients who are unsuitable for chemo-immunotherapy.

In August 2021, the Swiss Agency for Therapeutic Products (Swissmedic) granted orphan drug status to Brukinsa and accepted a marketing authorisation application for the drug for WM treatment. The drug is currently under regulatory review in Australia, Taiwan and South Korea for the treatment of WM.

Health Canada approved Brukinsa for the treatment of WM and MCL in March 2021 and July 2021 respectively.

The drug was approved in China for chronic lymphocytic leukaemia (CLL) / small lymphocytic lymphoma (SLL) and MCL in June 2020, and for WM in June 2021.

In September 2021, the FDA extended the label of Brukinsa for WM, having accepting a supplemental new drug application (sNDA) for the drug for the treatment of adult patients with WM in February 2021.

Waldenstrom’s macroglobulinaemia causes and symptoms

WM is a rare and incurable blood cancer that predominantly affects the bone marrow. It is a type of non-Hodgkin lymphoma that accounts for around 1% of all occurrences.

The disease starts in B-cells and disrupts normal blood cell formation by building up macroglobulin (abnormal proteins) in the bone marrow with the progression of the disease.

WM is more prevalent in men than in women and most commonly affects elderly individuals. Common symptoms of WM include weakness, appetite loss, fever, sweats, loss of weight and neuropathy.

Brukinsa mechanism of action

Brukinsa is a small-molecule, orally active BTK inhibitor that covalently binds with a cysteine residue in the BTK’s active site, inactivating the enzyme irreversibly and inhibiting BTK activity.

BTK is an essential component of the B-cell receptor (BCR) signalling pathways. The BCR signalling controls cell proliferation and survival in various B-cell malignancies.

BTK inhibitors prevent BCR-induced BTK activation and downstream signalling, inhibiting the growth of and ultimately killing malignant B-cells.

Clinical trials on Brukinsa

The FDA’s approval of Brukinsa for WM was based on positive safety and efficacy results from 351 WM patients in a Phase III randomised, open-label, multi-centre clinical trial named ASPEN.

The approval was also supported by data from a Phase II clinical trial conducted in China, as well as a global Phase I/II clinical trial conducted in patients with B-cell malignancies. The drug’s safety profile was also supported by the data drawn from 779 patients in six clinical trials of Brukinsa.

In the ASPEN trial, Brukinsa was compared against ibrutinib in patients with MYD88 L265P mutation (MYD88MUT) WM. The first cohort included 201 patients, who were randomised to receive either Brukinsa 160mg twice daily or ibrutinib 420mg once daily until disease progression or unacceptable toxicity.

The second cohort included patients with MYD88 wildtype (MYD88WT) or MYD88 mutation unknown WM, who were given Brukinsa 160mg twice daily.

The primary endpoint of the study was the proportion of patients achieving a very good partial response (VGPR) in cohort one as assessed by an independent review committee (IRC) according to modified sixth International Workshop on Waldenstrom’s Macroglobulinaemia (IWWM-6) response criteria (Treon 2015). An additional outcome measure was the duration of response (DoR).

A VGPR was achieved in around 28% of patients treated with Brukinsa, compared with 19% of patients treated with ibrutinib based on the modified IWWM-6 response criteria. The VGPR rate was 16% for Brukinsa, compared with 7% for ibrutinib based on IWWM-6 response criteria.

A 50% response rate (CR+VGPR+PR) was achieved in the second cohort, as assessed by IRC using IWWM-6 or modified IWWM-6. The DoR at 12 months was 94% with Brukinsa and 88% with ibrutinib.

The most common adverse reactions reported in patients during the trial were neutropaenia, upper respiratory tract infection, decreased platelet count, rash, haemorrhage, musculoskeletal pain, decreased haemoglobin levels, bruising, diarrhoea, pneumonia and cough.

Related Projects