Acalabrutinib (Calquence, AstraZeneca) and zanubrutinib (Brukinsa, BeiGene) are covalent, second-generation BTK inhibitors. 

When are Acalabrutinib and Zanubrutinib Used?

Acalabrutinib and zanubrutinib are indicated for the treatment of CLL in treatment-naïve patients (newly diagnosed) or relapsed/refractory patients (those who have had previous therapy).

How do Acalabrutinib and Zanubrutinib Work?

Acalabrutinib and zanubrutinib work by targeting and inhibiting BTK to interfere with the survival and proliferation of CLL cells. They both bind covalently to the same cysteine residue (Cys481), which is irreversible. 

Acalabrutinib is highly selective for BTK with minimal off-target effects, potentially resulting in a different side effect profile than zanubrutinib.

The two medicines have different pharmacokinetic properties, including differences in their absorption, distribution, metabolism, and elimination, which can affect dosing schedules and side effects.

How are Acalabrutinib and Zanubrutinib Administered?

Both of these medications are taken orally, in the form of tablets.  

• The standard dosage for acalabrutinib is 100 mg, taken twice daily.
• The standard dosage for zanubrutinib is 160 mg taken twice daily or 320 mg once daily, depending on the patient’s condition and tolerability.

How Effective are Acalabrutinib and Zanubrutinib for CLL?  

Acalabrutinib

A 2023 ELEVATE-TN Trial analysis examined the effectiveness of acalabrutinib combined with obinutuzumab for CLL patients as their first therapy.

After 6 years from the start of treatment:

• 78% of patients on this combination continued to have a response to the treatment with no CLL progression.
• For those taking acalabrutinib as a monotherapy (by itself), 62% of patients continued to have a response to the treatment with no CLL progression.

Zanubrutinib

A 2022 retrospective study examined the efficacy of zanubrutinib in CLL patients after 4 years of therapy. 

• 79% of CLL patients with del(17p) taking zanubrutinib continued to have a response to the treatment with no CLL progression.
• 82% of CLL patients without del(17p) taking zanubrutinib continued to have a response to the treatment with no CLL progression.

Side Effect Profile

Acalabrutinib 

The percentage of CLL patients who experience mild-moderate versions of common side effects from acalabrutinib is shown below. 

Side Effect	Percentage of Patients Affected
Infection	51%
Anemia	43%
Headache	37.9%
Upper respiratory tract infections	35%
Diarrhea	34.4%
Musculoskeletal pain	30.9%
Thrombocytopenia	28.6%
Rash	24.4%
Nausea	22%
Fatigue	21.9%
Bruising	21%

 

Zanubrutinib 

The percentage of CLL patients who experience mild-moderate versions of common side effects from zanubrutinib is shown below. 

Side Effect	Percentage of Patients Affected
Upper respiratory tract infection	25.8%
Musculoskeletal pain	25.4%
Hemorrhage	21.5%
Neutrophils decreased	28%
Platelets decreased	28%
Hemoglobin decreased	24%
Rash	18.8%
Bruising	16%

 

For more information on these side effects, you can visit the Side Effects Management section of this guide. 

For more information on these therapies, check out the sources below.

Sources: 

• Calquence Prescribing Information
• Brukinsa Prescribing Information

Financial Resources for Zanubrutinib and Acalabrutinib

To locate financial resources for zanubrutinib and acalabrutinib, click here to visit the financial support section of the guide.