CALQUENCE® (acalabrutinib) tablet formulation approved in the US across current indications
AstraZeneca has received FDA approval for a new tablet formulation of CALQUENCE (acalabrutinib) to treat chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and relapsed or refractory mantle cell lymphoma (MCL). The tablet is bioequivalent to the existing capsule formulation, offering the same efficacy and safety profile with the added benefit of co-administration with gastric acid-reducing agents. The approval follows positive results from the ELEVATE-PLUS trials, emphasizing the need for tailored treatment options for patients, particularly those with multiple conditions.
- FDA approval for new CALQUENCE tablet formulation expands treatment options.
- Tablet formulation allows co-administration with gastric acid-reducing agents.
- Bioequivalence to capsules ensures consistent efficacy and safety.
- Continued approval for MCL indication is contingent on further clinical benefit verification.
New formulation can be co-administered with gastric acid-reducing agents
Tablet offers efficacy, safety and consistent dosing compared to current capsule
The approval by the
In the trials, results showed the CALQUENCE capsule and tablet formulations are bioequivalent, indicating the same efficacy and safety profile can be expected with the same dosing strength and schedule.1 The tablet can be taken with gastric acid-reducing agents, including proton pump inhibitors (PPIs), antacids and H2-receptor antagonists (H2RAs).1,2 The majority of observed adverse events (AEs) in these studies were mild with no new safety concerns identified.1
CALQUENCE is also approved as a capsule formulation for the same indications as the tablet in the US and in many other countries worldwide.3 Indications may vary by market.
INDICATIONS AND USAGE
CALQUENCE is a Bruton tyrosine kinase (BTK) inhibitor indicated for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.
This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
CALQUENCE is also indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
IMPORTANT SAFETY INFORMATION ABOUT CALQUENCE® (acalabrutinib) tablets
Serious and Opportunistic Infections
Fatal and serious infections, including opportunistic infections, have occurred in patients with hematologic malignancies treated with CALQUENCE.
Serious or Grade 3 or higher infections (bacterial, viral, or fungal) occurred in
Hemorrhage
Fatal and serious hemorrhagic events have occurred in patients with hematologic malignancies treated with CALQUENCE. Major hemorrhage (serious or Grade 3 or higher bleeding or any central nervous system bleeding) occurred in
Use of antithrombotic agents concomitantly with CALQUENCE may further increase the risk of hemorrhage. In clinical trials, major hemorrhage occurred in
Consider the benefit-risk of withholding CALQUENCE for 3-7 days pre- and post-surgery depending upon the type of surgery and the risk of bleeding.
Cytopenias
Grade 3 or 4 cytopenias, including neutropenia (
Second Primary Malignancies
Second primary malignancies, including skin cancers and other solid tumors, occurred in
Atrial Fibrillation and Flutter
Grade 3 atrial fibrillation or flutter occurred in
ADVERSE REACTIONS
The most common adverse reactions (≥
*Treatment-emergent decreases (all grades) of hemoglobin (
Dose reductions or discontinuations due to any adverse reaction were reported in
The most common adverse reactions (≥
*Treatment-emergent decreases (all grades) of hemoglobin, platelets, and neutrophils were based on laboratory measurements and adverse reactions.
In patients with previously untreated CLL exposed to CALQUENCE, fatal adverse reactions that occurred in the absence of disease progression and with onset within 30 days of the last study treatment were reported in
Adverse reactions led to CALQUENCE dose reduction in
In patients with relapsed/refractory CLL exposed to CALQUENCE, serious adverse reactions occurred in
Adverse reactions led to CALQUENCE dose reduction in
DRUG INTERACTIONS
Strong CYP3A Inhibitors: Avoid co-administration of CALQUENCE with a strong CYP3A inhibitor. If these inhibitors will be used short-term, interrupt CALQUENCE. After discontinuation of strong CYP3A inhibitor for at least 24 hours, resume previous dosage of CALQUENCE.
Moderate CYP3A Inhibitors: Reduce the dosage of CALQUENCE to 100 mg once daily when co-administered with a moderate CYP3A inhibitor.
Strong CYP3A Inducers: Avoid co-administration of CALQUENCE with a strong CYP3A inducer. If co-administration is unavoidable, increase the dosage of CALQUENCE to 200 mg approximately every 12 hours.
SPECIFIC POPULATIONS
Based on findings in animals, CALQUENCE may cause fetal harm and dystocia when administered to a pregnant woman. There are no available data in pregnant women to inform the drug-associated risk. Advise pregnant women of the potential risk to a fetus.
Pregnancy testing is recommended for females of reproductive potential prior to initiating CALQUENCE therapy. Advise female patients of reproductive potential to use effective contraception during treatment with CALQUENCE and for 1 week following the last dose of CALQUENCE.
It is not known if CALQUENCE is present in human milk. Advise lactating women not to breastfeed while taking CALQUENCE and for 2 weeks after the last dose.
Avoid use of CALQUENCE in patients with severe hepatic impairment (Child-Pugh class C). No dosage adjustment of CALQUENCE is recommended in patients with mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment.
Please see full Prescribing Information, including Patient Information.
Notes
CLL
CLL is the most prevalent type of leukemia in adults, with over 100,000 new cases globally in 2019 and an estimated 20,160 new cases in the US in 2022.4,5 Although some people with CLL may not experience any symptoms at diagnosis, others may experience symptoms, such as weakness, fatigue, weight loss, chills, fever, night sweats, swollen lymph nodes and abdominal pain.6
In CLL, there is an accumulation of abnormal lymphocytes within the bone marrow. As the number of abnormal cells increases, there is less room within the marrow for the production of normal white blood cells, red blood cells and platelets. This could result in anemia, infection and bleeding.7 B-cell receptor signaling through BTK is one of the essential growth pathways for CLL.
MCL
MCL is an uncommon subtype of B-cell non-Hodgkin lymphoma.8 MCL comprises about 3
ELEVATE-PLUS
ELEVATE-PLUS is comprised of three Phase I, open-label, single-dose, cross-over studies conducted in 116 healthy subjects. The trials established bioequivalence between acalabrutinib tablets (100 mg) and acalabrutinib (100 mg) capsules, evaluated the PPI effect of acalabrutinib tablets administered in the presence versus absence of PPI rabeprazole and investigated the effect of food by comparing acalabrutinib tablets administered with a high-fat diet versus fasted.1
CALQUENCE
CALQUENCE (acalabrutinib) is a next-generation, selective inhibitor of Bruton’s tyrosine kinase (BTK). CALQUENCE binds covalently to BTK, thereby inhibiting its activity.3,10 In B cells, BTK signaling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis and adhesion.3
CALQUENCE is available for prescribing in capsule and tablet formulations in the US. CALQUENCE tablets and capsules are approved in the US for the treatment of CLL and SLL, and for the treatment of adult patients with MCL who have received at least one prior therapy.2,3 Capsules have restrictions in relation to use with gastric acid-reducing agents. The tablets are not licensed in the
CALQUENCE capsules are approved for CLL in the EU and many other countries worldwide and approved in
In the US and several other countries, CALQUENCE capsules are also approved for the treatment of adult patients with MCL who have received at least one prior therapy. The US MCL indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. CALQUENCE is not currently approved for the treatment of MCL in
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References
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Sharma S, Pepin X, Burri H, et al. New acalabrutinib formulation enables co-administration with proton pump inhibitors and dosing in patients unable to swallow capsules (ELEVATE-PLUS). [abstract and poster]. Poster presented at: 63rd
American Society of Hematology Annual Meeting and Exposition;December 11-14, 2021 ;Atlanta, Georgia . Abs 4365. -
CALQUENCE® (acalabrutinib) tablets [prescribing information].
Wilmington, DE ;AstraZeneca Pharmaceuticals LP ; 2022. -
CALQUENCE® (acalabrutinib) capsules [prescribing information].
Wilmington, DE ;AstraZeneca Pharmaceuticals LP ; 2019. -
National Cancer Institute (NCI). Cancer stat facts: leukemia — chronic lymphocytic leukemia (CLL). NCI website. AccessedAugust 2022 . https://seer.cancer.gov/statfacts/html/clyl.html - Yao Y, Lin X, Li F, et al. The global burden and attributable risk factors of chronic lymphocytic leukemia in 204 countries and territories from 1990 to 2019: analysis based on the global burden of disease study 2019. Biomed Eng Online. 2022;1:4. doi: 10.1186/s12938-021-00973-6
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American Cancer Society (ACS). Signs and symptoms of chronic lymphocytic leukemia. ACS website. AccessedAugust 2022 . https://www.cancer.org/cancer/chronic-lymphocytic-leukemia/detection-diagnosis-staging/signs-symptoms.html -
National Cancer Institute . Chronic lymphocytic leukemia treatment (PDQ®)–Patient version. NCI website. AccessedAugust 2022 . https://www.cancer.gov/types/leukemia/patient/cll-treatment-pdq - Cheah CY, Seymour JF and Wang ML. Mantle cell lymphoma. J Clin Oncol. 2016;34(11):1256-1269. doi: 10.1200/JCO.2015.63.5904
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MD Anderson Cancer Center . What to know about mantle cell lymphoma.MD Anderson Cancer Center website. AccessedAugust 2022 . https://www.mdanderson.org/cancerwise/what-to-know-about-mantle-cell-lymphoma-symptoms-diagnosis-and-treatment.h00-159385101.html - Wu J, Zhang M and Liu D. Acalabrutinib (ACP-196): a selective second-generation BTK inhibitor. J Hematol Oncol. 2016;9(21).
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FAQ
What new formulation of CALQUENCE was approved by AstraZeneca?
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Can CALQUENCE tablets be taken with gastric acid-reducing agents?
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