BRUKINSA^®▼ is a next-generation Bruton’s tyrosine kinase (BTK) inhibitor.⁶ It has high selectivity and potency towards BTK, resulting in sustained BTK inhibition, accompanied by low off-target binding.^6–9

BRUKINSA has demonstrated activity in several B-cell malignancies, with clinical benefit observed across patient subgroups.^6,10–12 Superiority versus another BTK inhibitor was demonstrated in the ALPINE study which enrolled patients with relapsed/refractory CLL.^10,11

BRUKINSA has demonstrated a favourable safety and tolerability profile across indications, including a low incidence of cardiovascular adverse events.^6,10–12

BRUKINSA is an oral monotherapy with a flexible dosing regimen, providing a convenient chemotherapy-free treatment.^6,12

Brukinsa therapeutic indications:

BRUKINSA as monotherapy is indicated for the treatment of adult patients with Waldenström’s macroglobulinaemia (WM) who have received at least one prior therapy, or in first line treatment for patients unsuitable for chemo-immunotherapy.¹²

BRUKINSA as monotherapy is indicated for the treatment of adult patients with marginal zone lymphoma (MZL) who have received at least one prior anti-CD20-based therapy.¹²

BRUKINSA as monotherapy is indicated for the treatment of adult patients with chronic lymphocytic leukaemia (CLL).¹²

BRUKINSA mechanism of action

B-cell receptor (BCR) signalling is essential for B cell development, differentiation, function and survival.^8,13 This signalling can become dysregulated, resulting in the development of B-cell malignancies such as CLL and WM.⁸

Bruton’s tyrosine kinase (BTK) is a signalling molecule of the BCR pathway, which is involved in
B-cell proliferation, trafficking, chemotaxis, and adhesion.^8,12,14 Targeted inhibition of BTK is one strategy that may be employed in the management of B-cell malignancies.^8,12,14

BRUKINSA is a next-generation BTK inhibitor.⁶ It has high selectivity and potency towards BTK, resulting in sustained BTK inhibition, accompanied by low off-target binding.^6–9

BRUKINSA binds to cysteine 481 (Cys481) in the BTK active site through formation of an irreversible covalent bond.^8,12 High median steady-state BTK occupancy was demonstrated in peripheral blood mononuclear cells (PBMCs) when dosed in patients with B-cell malignancies.¹² BRUKINSA also exhibited 94% to 100% occupancy in lymph nodes.¹² Furthermore, this high level of BTK occupancy is sustained for more than 24 hours, indicating deep and durable BTK inhibition.⁸

BRUKINSA is highly selective for BTK versus other TEC, EGFR and Src-family kinases.⁹ Furthermore, it has shown greater BTK selectivity versus ibrutinib.^7,9

This short video explains the role of BTK in health and disease. It then proceeds to discuss BTK inhibition and the effect of BRUKINSA.