Without any benefit in terms of effectiveness, AstraZeneca aims to deflect doctors from Imbruvica, the market leader of AbbVie and Johnson & Johnson, by touting a better safety profile for its rival, the BTK inhibitor, Calquence.
In a controlled clinical trial for previously treated chronic lymphocytic leukemia (CLL), a significantly lower number of patients who took Calquence suffered from atrial fibrillation than those who took Imbruvica, AstraZeneca revealed at the American Society of Clinical Oncology (ASCO) annual meeting.
A total of 9.4% of Calquence patients suffered from atrial fibrillation, a cardiac arrhythmia 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 directly harm patients, but also cause them to stop treatment, John Byrd, MD, the lead investigator of the face-to-face trial, said in a statement. In total, side effects led 14.7% of patients to discontinue treatment with Calquence, less than the 21.3% with Imbruvica. The data provides “compelling evidence” that Calquence is a more tolerable option for LLC, he added.
Since patients with CLL generally respond well to BTK inhibitors such as Calquence and therefore have to stay on medication for many years, it is important to have a tolerability advantage, explained Dave Fredrickson, business leader. AZ oncology, during an interview before the presentation of the data. “We believe this data will be an important consideration as physicians reflect on … their choice of what to [BTK] agent to use, âhe said.
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In terms of efficacy, the two drugs showed no difference after a median follow-up of 40.9 months, with patients in both arms experiencing a median duration of 38.4 months without disease progression.
But as SVB Leerink analysts noted a few days ago, Calquence’s data “still leaves room for BeiGene’s Brukinsa to be a safer option.”
BeiGene also recently touted Brukinsa’s own head-to-head victory over Imbruvica in relapsed or refractory CLL or small lymphocytic lymphoma in the Alpine Phase 3 trial. At a median follow-up of 15 months, significantly fewer Brukinsa takers – 2.5% to be exact – suffered from atrial fibrillation compared to 10.1% Imbruvica, according to data to be presented at the next meeting of the European Hematology Association.
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Although BeiGene’s victory further validates the idea that next-generation BTKs offer an improved side-effect profile, he followed the trial for a shorter period, noted Fredrickson. In addition to having long-term clinical trial follow-up, âphysicians are having their own positive real-world experiences with [Calquence], and we think that’s just as important, âhe added. Currently, nearly four in ten new patients starting a BTK inhibitor are on Calquence, he said.
Ironically, longer clinical follow-up and real-world experience is what J&J uses to defend Imbruvica against the new agents; after all, Imbruvica was the first BTK inhibitor to hit the market. It is possible that the rates of various side effects will increase as more patients are treated, Craig Tendler, vice president of clinical development in oncology and global medical affairs at J&J’s Janssen unit, said in an interview.
In addition, he pointed out, trials of AZ and BeiGene have been conducted on previously treated patients, while Imbruvica – along with the BTK class – has been established as the standard of primary care. 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.