Ned Pagliarulo, BioPharma Dive
A Phase 3 trial testing AstraZeneca’s Calquence in previously treated chronic lymphocytic leukemia will be stopped early, after an interim analysis found patients on the blood cancer therapy were doing significantly better than those receiving one of two combination regimens containing the commonly used drug Rituxan.
According to AstraZeneca, treatment with Calquence led to a statistically significant and “clinically meaningful” improvement in progression free survival compared to Rituxan plus either Gilead’s Zydelig or the chemotherapy bendamustine.
The news gives a lift to the British pharma’s hopes for the drug, which was approved in late 2017 for a type of lymphoma. While AstraZeneca has seen success with its drugs for solid tumors, its blood cancer business rests entirely on Calquence.
AbbVie and Johnson & Johnson’s Imbruvica (ibrutinib) has quickly become a standard choice in chronic lymphocytic leukemia, a blood cancer that begins in the bone marrow and mainly affects older adults.
Four late-stage studies have read out positive for Imbruvica, including two in the first-line setting. That’s led to steady gains in market share for the drug and a recent endorsement in treatment guidelines from the National Comprehensive Cancer Network.
Commercially, the drug has become a top-seller for AbbVie, earning more than $1 billion for the drugmaker in the first quarter of 2019.
Calquence (acalabrutinib) is a would-be rival. Both drugs inhibit a protein called Bruton’s tyrosine kinase, which is crucial for the development of white blood cells known as B cells.
AstraZeneca gained access to Calquence in 2016, when it spent $4 billion for a majority stake in Acerta Pharma.
The drug was first approved in November 2017 for mantle cell lymphoma, and AstraZeneca hopes to soon expand into CLL as well.
The early success reported Tuesday, from a study called ASCEND or ACE CL-309, should help that goal.
The open-label trial enrolled 310 patients, who were randomized to either Calquence or doctor’s choice of Rituxan (rituxumab) plus Zydelig (idealisib) or the older chemotherapy bendamustine.
AstraZeneca gave few details beyond the significant improvement in progression-free survival, but did note that the safety profile of Calquence was consistent with past results. Full results will be presented at a future medical meeting.
The pharma is also expecting results this year from another Phase 3 study, ACE CL-007, that tests Calquence in first-line CLL.
Even if that and other studies are successful, however, catching Imbruvica will be a challenge. AbbVie and J&J have established a high bar for efficacy and analysts view the drug as the preferred option currently for most CLL patients.
In the near term, AstraZeneca’s oncology business will remain driven by its new drugs for solid tumors, namely Tagrisso (osimertinib), Imfinzi (durvalumab) and Lynparza (olaparib).