A recent article in BioPortfolio carried AstraZeneca’s announcement of the FDA’s approval of CALQUENCE® (acalabrutinib) for adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
The approval was given as a result of two clinical trials. Astra conducted the ELEVATE-TN Phase III trial that involved patients who have not yet been treated for CLL
ASCEND, the second Phase III trial, involved patients whose CLL had relapsed or had been resistant to treatment (refractory).
The FDA’s interim analysis was conducted on the combination of CALQUENCE together with the drug obinutuzumab or CALQUENCE administered alone.
Its findings showed a marked reduction in death or progression of disease in patients with untreated, relapsed, or refractory CLL. The results for patients in these two groups were compared against obinutuzumab plus chlorambucil chemotherapy administered to the trial’s control group.
The FDA’s findings were ninety and eighty percent respectively.
In both trials, CALQUENCE evidenced tolerability and safety consistent with results from its previous trials. The ELEVATE-TN trial’s lead author, Jeff Sharman, M.D., explained that tolerability presents a problem for patients with CLL. When comparing CALQUENCE to current treatments, CALQUENCE showed a marked improvement not only in progression-free survival, but in safety and tolerability as well.
FDA Project Orbis
The FDA’s approval of CALQUENCE has been granted in accordance with Project Orbis. This project is part of the FDA Oncology Center of Excellence.
The Center sets out guidelines for review and submission by international partners relating to oncology medicine and collaborates with its Australian and Canadian partners.
Median Time to Disease Progression
The established time for progression of the disease when obinutuzumab plus chlorambucil are administered is twenty-two months.
But the same benchmark has not yet been reached for CALQUENCE plus obinutuzumab or CALQUENCE as a single agent.
About Chronic Lymphocytic Leukemia (CLL)
In 2019 there were 20,720 newly reported cases of CLL in the United States and 105,000 cases reported worldwide.
The number of CLL patients may increase as a result of new and improved therapy accounting for longer overall survival.
CLL is categorized by an abundance of blood stem cells in bone marrow that form abnormal lymphocytes that have little resistance to infections.
These lymphocytes crowd out healthy red and white blood cells and platelets. That leaves the patient prone to various infections, anemia and excessive bleeding.
A total of 1,029 patients were treated with 100mg CALQUENCE every twelve hours. The patients, who presented with hematologic malignancies, were grouped in several clinical trials.
Eighty-eight per cent of the patients were treated for a minimum of six months. Seventy-nine per cent of patients were treated for a minimum of one year.
Side effects experienced by the participants included:
- Atrial fibrillation
- Bleeding and/or central nervous system bleeding
- Fatal hemorrhage (occurred in 0.1%)
- Secondary malignancies
Ongoing Clinical Trials
Acerta and AstraZeneca are currently conducting twenty-three clinical trials for CALQUENCE through their extensive development program. Multiple phase III trials will include ELEVATE-TN, ASCEND AND ELEVATE-RR. The drug will be evaluated in conjunction with several other agents. The companies are focusing on B-cell blood cancers and hematologic malignancies.