BRUKINSA: a next-generation BTK inhibitor

BRUKINSA, a next-generation BTK inhibitor, is a recommended treatment option by NICE and its use is accepted by SMC and HSE for adult patients with CLL in treatment-naïve and relapsed/refractory (R/R) settings — a decision that is supported by robust data from multiple clinical studies​[1–7]​.

CLL is a growing global concern​[8–11]​

Incidence, morbidity and mortality have all significantly increased globally from 1990 to 2019 and are projected to rise​[8–11]​.

Despite the availability and choice of multiple therapy options, improvements are needed to address tolerability issues and reduce the risk of developing treatment resistance​[12,13]​. Additionally, some patients are at risk of sub-optimal outcomes, particularly those with high-risk genetic features such as unmutated IGHV, mutated TP53 and deletion of the short arm of chromosome 17 (del[17p])​[14]​.

BRUKINSA is an oral BTK inhibitor that has demonstrated superior PFS vs BR in treatment-naïve CLL and vs ibrutinib in R/R CLL. It has shown consistent and durable efficacy across lines of therapy and subgroups, including patients with unmutated IGHV, del(17p) and/or TP53 mutation. Its use is supported by robust efficacy and safety data and unmatched dosing flexibility among BTK inhibitors​[1,6,7,14–16]​.

BRUKINSA: Reimbursed and available…​[3–5]​

…in England and Wales

…in Scotland

…in Ireland

BRUKINSA has demonstrated superior efficacy vs BR in treatment-naïve CLL​[6]​

SEQUOIA was a pivotal Phase 3 trial of BRUKINSA in treatment-naïve CLL​[1,6]​

In SEQUOIA, patients without del(17p) were assigned to Cohort 1 and randomly assigned 1:1 to receive BRUKINSA 160 mg BID or BR for a maximum of 6 cycles (n=241 and n=238, respectively). Patients with del(17p) were assigned to Cohort 2 and received BRUKINSA (n=111; single-arm). Cohort 2 was analysed separately​[6]​.

The primary endpoint was PFS (IRC-assessed) in Cohort 1. Secondary endpoints included ORR, PFS, and OS​[6]​.

With a median follow-up of 25.0 months, BRUKINSA demonstrated superior PFS vs BR in patients without del(17p)​[1,6]​

With extended follow-up, patients without del(17p) treated with BRUKINSA continued to demonstrate a PFS benefit vs BR. mPFS was NE vs 42.2 months (95% CI 38.4, 49.8) for BRUKINSA vs BR, respectively (investigator-assessed, median follow-up 43.7 months). PFS was significantly improved with BRUKINSA vs BR regardless of IGHV mutational status​[17]​.

With a median follow-up of 30.5 months, PFS at 24 months in patients with del(17p) was 89%​[6]​. With a median follow-up of 47.9 months, efficacy was maintained — PFS at 42 months was 79%​[17]​.

ORRs were higher with BRUKINSA vs BR in patients without del(17p), at 95% (95% CI 91.0, 97.1) and 85% (95% CI 80.1, 89.5), respectively (IRC-assessed, median follow-up 25 months). Results were consistent across all prespecified subgroups and in Cohort 2​[1,6]​.

BRUKINSA had a favourable safety profile in both cohorts, including a low incidence of atrial fibrillation and flutter. Additionally, fewer patients discontinued or reduced BRUKINSA due to AEs in both cohorts​[6]​.

For further study information, see BRUKINSA.co.uk (clicking on this link directs you to a promotional website containing information on BRUKINSA).

ALPINE was the pivotal Phase 3 trial of BRUKINSA in R/R CLL that demonstrated PFS superiority vs ibrutinib​[1,7]​

ALPINE is the first and only BTK inhibitor clinical trial to show superior efficacy vs ibrutinib in R/R CLL​[7,18]​

In ALPINE, 652 patients were randomised to receive BRUKINSA 160 mg BID (n=327) or ibrutinib 420 mg QD (n=325). The primary endpoint was ORR (investigator-assessed). Key secondary endpoints included PFS, DoR, OS and incidence of atrial fibrillation/flutter​[7]​.

With a median follow-up of 29.6 months, BRUKINSA demonstrated superior ORR vs ibrutinib (80% vs 71% for BRUKINSA vs ibrutinib, respectively, in the ITT population; investigator-assessed; superiority two-sided: p=0.0133)​[7,18]​.

Response rates were consistently higher with BRUKINSA vs ibrutinib across patient subgroups​[7]​.

With a median follow-up of 29.6 months, BRUKINSA demonstrated superior PFS vs ibrutinib, with a 35% relative risk reduction (HR=0.65, 95% CI 0.49, 0.86; p=0.002; investigator-assessed)​[7]​.

With extended follow-up, BRUKINSA continued to demonstrate sustained superior clinical benefit in both ORR and PFS vs ibrutinib. The 48-month ORR was 90% with BRUKINSA vs 83% with ibrutinib​[19]​.

BRUKINSA demonstrated sustained PFS superiority vs ibrutinib with a median follow-up of 39 months in patients with R/R CLL (HR=0.68 [95% CI: 0.53, 0.86]; two-sided descriptive p=0.0011)​[19]​

BRUKINSA was well tolerated. Lower rates of cardiac disorders vs ibrutinib were observed, and there were no cardiac deaths in the BRUKINSA arm, whereas 6 patients who received ibrutinib had a fatal cardiac event. Lower rates of atrial fibrillation/flutter were observed with BRUKINSA vs ibrutinib (7% vs 16%, respectively). Rates of hypertension were 27% vs 25% (all-grade) and 16% vs 15% (grade ≥3) for BRUKINSA vs ibrutinib, respectively. Fewer patients discontinued or reduced their dose with BRUKINSA due to AEs​[19]​.

For further study information, see BRUKINSA.co.uk (clicking on this link directs you to a promotional website containing information on BRUKINSA).

BRUKINSA’s favourable safety profile is well documented and consistent across indications​[1]​

BRUKINSA as monotherapy has been evaluated in 1,550 patients in clinical trials, including patients with CLL, Waldenström’s macroglobulinaemia, marginal zone lymphoma, mantle cell lymphoma, follicular lymphoma and other types of B-cell malignancies (median duration of exposure: 34.41 months)​[1]​*.

Of the 1,550 patients treated with zanubrutinib, 4.8% of patients discontinued treatment due to adverse reactions. The most frequent adverse reaction leading to treatment discontinuation was pneumonia (2.6%). Adverse reaction leading to dose reduction occurred in 5.0% of patients​[1]​. Refer to the BRUKINSA SmPC for complete safety information.

BRUKINSA has flexible and convenient dosing​[1]​

BRUKINSA is an oral therapy that is taken daily until disease progression or unacceptable toxicity. Treatment with BRUKINSA offers once-daily or twice-daily dosing options​[1]​.

BRUKINSA can be co-administered with PPIs and H2RAs without compromising efficacy and can be dose adjusted for patients who are taking moderate and strong CYP3A inhibitors​[1]​.

No specific dose adjustment is required for elderly patients (≥65 years old) taking BRUKINSA​[1]​.

Refer to the BRUKINSA SmPC for complete information before initiating therapy with BRUKINSA.

Find out more about BRUKINSA for the treatment of your patients with CLL

Click here for BRUKINSA prescribing information

▼ This medicine is subject to additional monitoring. This will allow quick identification of new safety information. Report any suspected adverse reactions.

*BRUKINSA as monotherapy is not approved in the UK or Ireland for the treatment of patients of with follicular lymphoma or mantle cell lymphoma​[1]​.

Abbreviations
AE, adverse event; BID, twice daily; BR, bendamustine-rituximab; BTK, Bruton’s tyrosine kinase; CI, confidence interval; CLL, chronic lymphocytic leukemia; CR, complete response; CYP3A, Cytochrome P450, family 3, subfamily A; del(17p), deletion of the short arm of chromosome 17; DoR, duration of response; FCR, fludarabine, cyclophosphamide and rituximab; H2RA, histamine H2-receptor antagonist; HR, hazard ratio; HSE, Health Service Executive; IGHV, immunoglobulin heavy chain variable region genes; IRC, independent review committee; ITT, intention-to-treat; mPFS, median progression-free survival; MZL, marginal zone lymphoma; NE, non-evaluable; NICE, National Institute for Health and Care Excellence; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PPI, proton-pump inhibitor; PR, partial response; QD, once daily; R/R, refractory/relapsed; SMC, Scottish Medicines Consortium; SmPC, Summary of Product Characteristics; TP53, tumour protein P53; WM, Waldenström’s macroglobulinaemia.

1223-BRU-PRC-031 | March 2024