The Brukinsa difference is
Complete BTK Inhibition

With optimized potency, bioavailability, and selectivity, BRUKINSA was designed to completely shut off BTK.1,2

Brukinsa achieves 100% inhibition*

BTK Inhibition
Median Steady-State
BRUKINSA‡1
100
Acalabrutinib3
≥95
Ibrutinib4
>90

*The clinical significance of 100% inhibition has not been established.

The clinical significance of in vivo and in vitro studies has not been established. Mechanism of action statements are not meant to imply efficacy and safety.

Inhibition in peripheral blood mononuclear cells is 100% with both BID and QD dosing, and inhibition in lymph nodes is 100% with BID dosing and 94% with QD dosing.

BRUKINSA has high potency AND AFFINITY FOR BTK§

Concentration Levels Needed to Inhibit BTK (IC50 [nM])¶5
BRUKINSA
0.5
±
0.0
Ibrutinib
1.5
±
0.2
Acalabrutinib
5.1
±
1.0

BRUKINSA also has minimal off-target binding
to other tyrosine kinases.6

§The clinical significance of in vivo and in vitro studies has not been established. Mechanism of action statements are not meant to imply efficacy or safety.

The IC50 reflects the median inhibitory concentration required by each drug to achieve 50% inhibition.7

BRUKINSA MAINTAINS THERAPEUTIC
CONCENTRATIONS OVER 24 HOURS#**

BRUKINSA5,8

Ibrutinib††5,8

Acalabrutinib††5,8

Sustained inhibition is relevant because BTK is continuously synthesized.9

#The IC50 reflects the median inhibitory concentration required by each drug to achieve 50% inhibition.7

**The clinical significance of in vivo and in vitro studies has not been established. Mechanism of action statements are not meant to imply efficacy or safety. These data are from separate preclinical analyses. Limitations of cross comparisons apply.

††Plasma concentrations of ibrutinib and acalabrutinib remain lower than their respective IC50 values for significant periods of time even when taking their active metabolites into consideration.

BRUKINSA activity is unaffected by
gastric acid reducing agents

Effects of Coadministration of Gastric Acid Reducing Agents on Drug Activity
BRUKINSA1 Ibrutinib4 Acalabrutinib3
Proton Pump
Inhibitors (PPIs)
Exposure
not affected
Exposure
not affected
Reduction in exposure­—
avoid coadministration
H2-Receptor
Antagonists
(H2RAs)
Exposure
not affected
Exposure
not affected
Reduction in exposure­—
take 2 hours before H2RA
Antacids Exposure
not affected
Exposure
not affected
May reduce activity—
separate by 2 hours

20%-55% of cancer patients receive gastric acid reducing agents.10,11

BID=twice a day; BTK=Bruton’s tyrosine kinase; Ctrough=trough concentration;
IC50=50% inhibitory concentration; QD=once a day.

The Brukinsa Difference

Designed to meet the challenges
of BTK inhibition

1

Complete BTK inhibition‡‡

Highly potent with a high affinity for BTK§§1,2

2

24-HOUR INHIBITION SUSTAINED
at therapeutic concentrations

BRUKINSA was demonstrated to stay above the IC50 threshold for 24 hours2

3

ACTIViTY NOT AFFECTED BY
GASTRIC ACID REDUCING AGENTS

Can be coadministered with PPIs, H2RAs, and antacids1

4

Minimal off-target binding

High affinity for BTK with minimal off-target binding to other tyrosine kinases including EGFR, FGR, FRK, HER2, HER4, ITK, JAK3, LCK, and TEC6

‡‡The clinical significance of 100% inhibition has not been established.

§§Inhibition in peripheral blood mononuclear cells is 100% with both BID and QD dosing, and inhibition in lymph nodes is 100% with BID dosing and 94% with QD dosing.


BID=twice a day; BTK=Bruton’s tyrosine kinase; H2RAs=H2-receptor antagonists; IC50=50% inhibitory concentration; PPIs=proton pump inhibitors; QD=once a day.

Powerful and
Sustained Responses
Efficacy
Established
Safety Profile
Safety
Personalized
Patient Support
Patient Support