1. Market
The sales volume of zanubrutinib reached USD 160 million in 2020 and USD 450 million in the first three quarters of 2021.
2. RLD
|
Proprietary Name: |
Brukinsa |
Appl. No. : |
N213217 |
|
Dosage Form: |
Capsule |
Route/Dose: |
Oral, 160 mg orally twice daily or 320 mg orally once
daily |
|
Strength: |
80 mg |
Supply: |
120 capsules/bottle |
|
Ingredients: |
colloidal silicon dioxide, croscarmellose sodium,
magnesium stearate, microcrystalline cellulose and sodium lauryl sulfate. (in
a capsule) |
Indications: |
Mantle cell lymphoma, Waldenstrom’s Macroglobulinemia Marginal Zone Lymphoma, Chronic Lymphocytic Leukemia or
small lymphocytic lymphoma |
|
API Solubility |
The aqueous solubility of zanubrutinib is pH dependent,
from very slightly soluble to practically insoluble. The solubility of
zanubrutinib in ethanol and DMSO is approximately 5 mg/ml and approximately
10 mg/ml in DMF. |
Applicant Holder |
BEIGENE USA INC |
3. Treatment
•
Rituximab-based therapy is currently the
standard first-line
treatment for WM, while ibrutinib has emerged as an alternative.
•
First-line
treatment of MCL can be subdivided essentially into aggressive therapy or
less aggressive therapy depending on patient presentation and
comorbidities.
•
The most common types of first
line treatment for CLL are: targeted drugs (such as
acalabrutinib, ibrutinib, venetoclax and obinutuzumab) chemotherapy (such
as cyclophosphamide or fludarabine) These work in different ways to kill the
leukaemia cells.
• Zanubrutinib was designed with improved BTK selectivity, which may confer tolerability advantages over ibrutinib, particularly for treatment-limiting toxicities caused by the inhibition of off-target tyrosine kinases.
4. Clinically Significant Adverse Events- Hemorrhage
- Infections
- Cytopenias
- Second Primary Malignancies
- Cardiac Arrhythmias
- For a study of 53 patients with relapsed/refractory MZL (n = 20) and relapsed/refractory FL (n = 33), all of whom were received zanubrutinib at the recommended phase 2 dose.
- Treatment with zanubrutinib was generally well tolerated, with most adverse events being ≤ grade 2. However, 2 patients required dose reduction, and 4 patients discontinued treatment because of adverse events.
- In another report, 13.9% of zanubrutinib users require dose reduction, and 4% treatment discontinuation, caused by adverse events (AEs).
- The plasma protein binding of zanubrutinib is approximately 94%.
- The recommended dosage of BRUKINSA is 160 mg taken orally twice daily or 320 mg taken orally once daily until disease progression or unacceptable toxicity.
- Cmax and AUC increase proportionally over a dosage range from 40 mg to 320 mg.
- The median tmax of zanubrutinib is 2 hours.
- No food effect.
- Plasma protein binding ~94%.
- Half-life 2-4 h.
- primarily metabolized by cytochrome P450(CYP)3A.
- 87% of the dose was recovered in feces and 8% in urine.
- Co-administration of zanubrutinib with rifabutin* resulted in a less than 2-fold reduction of zanubrutinib exposures. ... Overall, zanubrutinib was well tolerated.
|
Patent No |
Patent Expiration |
Key Elements |
|
04/22/2034 |
Chemical patent |
|
|
04/22/2034 |
Treating B-cell proliferative disorder |
|
|
08/15/2037 |
A Crystal form (crystalline form exhibits an X-ray
powder diffraction pattern comprising diffraction peaks having 2 θ angle
values at 14.8±0.2°, 15.6±0.2°, 16.4±0.2° and 21.4±0.2°.) |
|
|
04/22/2034 |
Chemical patent |
|
|
08/15/2037 |
1. A method for treating mantle cell lymphoma in a
subject, comprising administering to the subject in need thereof a crystalline
form of Compound 1, X-ray: 2θ angle values at 14.8±0.2°, 15.6±0.2°,
16.4±0.2°, and 21.4±0.2°. |
|
|
01/19/2043 |
A method of treating .. B-cell proliferative disorder
comprising concomitantly administering zanubrutinib, and the moderate
CYP3A inducer |
- MSN Laboratories Private Ltd.
- Olon SPA
