The latest approval for Calquence, a Bruton tyrosine kinase inhibitor, was granted under the FDA’s Real-Time Oncology Review and newly established Project Orbis programs.
Two months after snagging Breakthrough Therapy Designation, AstraZeneca’s Calquence wins approval from the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
The latest approval for Calquence (acalabrutinib), a Bruton tyrosine kinase (BTK) inhibitor, was granted under the FDA’s Real-Time Oncology Review and newly established Project Orbis programs. Calquence binds covalently to BTK, thereby inhibiting its activity. In B-cells, BTK signaling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis and adhesion.
Throughout its clinical trial in this indication, Calquence has continuously flexed its muscles. Data from two separate Phase III trials, ASCEND and ELEVATE-TN, were used as the basis for the Breakthrough Therapy Designation as well as the approval. The ELEVATE-TN trial was halted in June after Calquence hit its endpoints following an interim analysis. Calquence combined with obinutuzumab and as monotherapy reduced the risk of disease progression or death by 90% and 80%, respectively in ELEVATE-TN. Full results of the interim analysis of that trial will be presented at the upcoming American Society of Hematology congress. Calquence met primary endpoints in patients with previously-untreated CLL, which is the most common type of leukemia in adults. In May, AstraZeneca halted the ASCEND trial early after the medication its endpoint at an interim analysis. Similar to the ELEVATE-TN study, ASCEND data showed that Calquence hit the mark in progression-free survival in previously-treated CLL patients. The ASCEND trial marked the first time a Bruton tyrosine kinase (BTK) inhibitor showed a benefit in CLL as a monotherapy.
Together, the trials showed that Calquence in combination with obinutuzumab or as a monotherapy significantly reduced the relative risk of disease progression or death versus the comparator arms in both 1st-line and relapsed or refractory CLL, AstraZeneca said.
Dave Fredrickson, head of AstraZeneca’s oncology business unit, said the approval of Calquence in these indications provides new hope for patients with one of the most common types of adult leukemia. He said this year alone, there are more than 20,000 new cases that will be diagnosed. Calquence, Fredrickson said, offers “outstanding efficacy and a favorable tolerability profile” for patients.
“The chronic lymphocytic leukemia patient population is known to face multiple comorbidities, and tolerability is a critical factor in their treatment,” Fredrickson said in a statement.
Jeff Sharman, lead author of the ELEVATE-TN trial and director of research at Willamette Valley Cancer Institute, added that tolerability is an issue in the current treatment landscape of CLL, particularly as many patients undergo therapy for years.
“In the ELEVATE-TN and ASCEND trials comparing Calquence to commonly used treatment regimens, Calquence demonstrated a clinically meaningful improvement in progression-free survival in patients across multiple settings, while maintaining its favorable tolerability and safety profile,” Sharman said in a statement.
The latest approval of Calquence is among the first to be granted under Project Orbis, an initiative of the FDA’s Oncology Center of Excellence, which provides a framework for concurrent submission and review of oncology medicines.
Calquence is also approved for the treatment of adults with relapsed or refractory mantle cell lymphoma (MCL) and is being developed for the treatment of CLL and other blood cancers. AstraZeneca is planning on seeking additional approvals for Calquence based on the two aforementioned clinical trials. When Calquence was first approved in 2017, AstraZeneca Chief Executive Officer Pascal Soriot said the drug would become a cornerstone in the company’s hematology pipeline.
