AstraZeneca's Targeted Therapy Calquence Receives FDA Breakthrough Therapy Designation for Chemotherapy-Free Treatment of Chronic Lymphocytic Leukemia

August 15, 2019 /Bio ValleyBIOON/ --Pharmaceutical GiantsAstraZeneca(AstraZeneca) recently announced that the U.S. Food and Drug Administration (FDA) has been granted Breakthrough Therapy Designation (BTD) for the targeted anticancer drug Calquence (acalabrutinib) as a monotherapy for the treatment of chronic lymphocyticLeukemia(Chronic Lymphocytic Leukemia [CLL]) adult patients. CLL is one of the most common types of leukemia in adults.

Notably, this BTD marks the 10th Breakthrough Therapy Designation that AstraZeneca has received from the FDA since 2014. The Breakthrough Therapy Designation is a new drug review pathway established by the FDA in 2012, aimed at accelerating the development and review of new drugs intended to treat serious or life-threatening conditions, where preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies. Investigational drugs granted BTD status are eligible for benefits includingFDACloser guidance, including from senior officials, to ensure that new treatment options are made available to patients in the shortest possible time.

This BTD is based on the positive interim analysis results from two Phase III clinical studies, ELEVATE-TN and ASCEND. The results demonstrated that Calquence, either as monotherapy or in combination, significantly prolonged progression-free survival (PFS) in patients, with a safety and tolerability profile consistent with its established characteristics.

——ASCEND Study:Conducted in patients with relapsed or refractory chronic lymphocytic leukemia (CLL), this study compared the efficacy and safety of Calquence versus physician’s choice of treatment, either IdR (rituximab plus idelalisib) or BR (rituximab plus bendamustine). The results showed that the study had already met its primary endpoint at the interim analysis: compared with physician’s choice of treatment, Calquence significantly prolonged progression-free survival (PFS) in patients with relapsed or refractory CLL. Data from a median follow-up of 16.1 months demonstrated that, compared with the IdR or BR regimens, Calquence treatment resulted in statistically and clinically significant improvements in PFS, with a 69% reduction in the risk of disease progression or death (HR=0.31, 95% CI: 0.20–0.49; p<0.0001). At the time of data analysis, the median PFS had not been reached in the Calquence group, whereas it was 16.5 months in the control group. At 12 months, 88% of patients in the Calquence group remained progression-free, compared with 68% in the control group.

—ELEVATE-TN Study:Conducted in previously untreated (treatment-naïve) patients with chronic lymphocytic leukemia (CLL), this study aimed to evaluate the efficacy and safety of Calquence monotherapy and Calquence plus obinutuzumab combination therapy relative to chlorambucil plus obinutuzumab combination therapy. The results showed that the study had already met its primary endpoint at the interim analysis: compared with the chemotherapy-based chlorambucil plus obinutuzumab regimen, the Calquence plus obinutuzumab combination therapy achieved a statistically significant and clinically meaningful improvement in progression-free survival (PFS). The study also met its key secondary endpoint; compared with the chemotherapy-based chlorambucil plus obinutuzumab regimen, Calquence monotherapy likewise demonstrated a statistically significant and clinically meaningful improvement in PFS.

AstraZenecaTumorJosé Baselga, Executive Vice President of Research and Development, stated: “This represents a significant regulatory milestone in hematology. The Breakthrough Therapy Designation (BTD) acknowledges the growing body of evidence supporting Calquence as a highly selective Bruton’s tyrosine kinase (BTK) inhibitor, offering patients a novel, differentiated, chemotherapy-free treatment option with a favorable safety profile.”

Calquence was approved in the United States in October 2017FDAAccelerated approval for adult patients with relapsed or refractory mantle cell lymphoma (MCL) who have previously received at least one therapy. Currently, the drug is being developed for the treatment of CLL and other hematologic malignancies.Tumor。

The active pharmaceutical ingredient of Calquence is acalabrutinib, a highly selective, potent, covalent Bruton’s tyrosine kinase (BTK) inhibitor that acts by irreversibly binding to and inhibiting BTK. BTK is a key regulator of the B-cell receptor (BCR) signaling pathway and is widely expressed in various types of hematologic malignancies, where it plays a role in B-cell proliferation, trafficking, chemotaxis, and adhesion, making it a therapeutic target for hematologic malignancies.Tumorimportant target. In preclinical studies, acalabrutinib demonstrated minimal off-target effects.

Currently, Calquence is being developed for multiple B-cell hematologic cancers, including chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma, Waldenström macroglobulinemia (WM), follicular lymphoma (FL), multiple myeloma, and other hematologic malignancies.TumorAstraZeneca has extremely high commercial expectations for Calquence, projecting that the drug’s peak sales could reach $5 billion!

Calquence shares the same mechanism of action as AbbVie/J&J’s blockbuster blood cancer drug Imbruvica (ibrutinib), the first BTK inhibitor approved globally. Since its initial approval in November 2013, Imbruvica has gained approval for up to 10 therapeutic indications across six disease areas, with global sales rising steadily. In June this year, pharmaceutical market research firm EvaluatePharma released a report predicting that Imbruvica’s global sales would reach $9.5 billion in 2024, making it the third best-selling oncology drug worldwide, after Keytruda and Opdivo. (Bioon.com)

Original source:AstraZeneca Website