Without an efficacy edge, AstraZeneca is aiming to lure doctors away from AbbVie and Johnson & Johnson’s market-leading Imbruvica by touting a better safety profile for its rival BTK inhibitor Calquence.
In a head-to-head clinical trial for previously treated chronic lymphocytic leukemia (CLL), a significantly lower number of patients who took Calquence suffered atrial fibrillation than did those who took Imbruvica, AstraZeneca revealed at the American Society of Clinical Oncology (ASCO) annual meeting.
A total of 9.4% of Calquence patients had atrial fibrillation, a cardiac arrythmia that can increase the risk of stroke, heart failure and other complications. The number for Imbruvica in the phase 3 ELEVATE-RR trial was 16%.
Heart problems can not only harm patients directly, it can also cause them to stop treatment, John Byrd, M.D., the lead investigator of the head-to-head trial, explained in a statement. All told, side effects led to 14.7% of patients discontinuing Calquence treatment, fewer than the 21.3% for Imbruvica. The data provide “compelling evidence” that Calquence is a more tolerable option for CLL, he added.
Because CLL patients typically respond well to BTK inhibitors such as Calquence and therefore need to stay on meds for many years, having a tolerability advantage is important, AZ’s oncology business chief Dave Fredrickson explained during an interview ahead of the data presentation. “We do think that these data will be an important consideration as physicians think about … their choice of what [BTK] agent to use,” he said.
On the efficacy front, the two drugs showed no difference after a median follow-up of 40.9 months, as patients in both arms lived a median 38.4 months without disease progression.
But as SVB Leerink analysts noted a few days ago, Calquence’s data still “leave room for BeiGene’s Brukinsa to be a safer option.”
BeiGene recently also touted its own Brukinsa head-to-head win against Imbruvica in relapsed or refractory CLL or small lymphocytic lymphoma in the phase 3 Alpine trial. At a median follow-up of 15 months, significantly fewer Brukinsa takers—2.5% to be exact—experienced atrial fibrillation versus Imbruvica’s 10.1%, according to data that will be presented at the upcoming European Hematology Association meeting.
While BeiGene’s win further validates the notion that next-generation BTKs offer an improved side effects profile, it has followed the trial for a shorter period of time, Fredrickson noted. Besides having a long-term follow-up from clinical trials, “physicians are having their own positive experiences in the real world with [Calquence], and we think that’s every bit as important,” he added. Currently, nearly four out of 10 new patients starting on a BTK inhibitor are with Calquence, he said.
Ironically, longer clinical follow-up and real-world experience are what J&J’s using to defend Imbruvica against the new agents; after all, Imbruvica was the first BTK inhibitor to reach the market. It’s possible the rates of various side effects could increase when more patients are treated, said Craig Tendler, vice president of oncology clinical development and global medical affairs at J&J’s Janssen unit, during an interview.
Besides, he pointed out, both AZ’s and BeiGene’s trials were conducted in previously treated patients, while Imbruvica—as well as the BTK class—has been established as a standard of care in the front-line setting. At ASCO, J&J and AbbVie presented updated data from the phase 3 RESONATE-2 trial for Imbruvica in newly diagnosed CLL with up to seven years of follow-up.