ASH: Jaypirca matches Imbruvica in first-line CLL trial

Hard on the heels of an FDA approval of Jaypirca as a second-line therapy for chronic lymphocytic leukaemia (CLL), Eli Lilly has revealed the data it hopes will make the drug an option for previously untreated patients.

The reversible BTK inhibitor was at least as effective as AbbVie/Johnson & Johnson's older, non-reversible drug Imbruvica (ibrutinib) in the BRUIN CLL-314 trial, which involved patients with CLL or small lymphocytic leukaemia (SLL) who were being treated for the first time, or had prior treatment that did not include a BTK inhibitor.

As it turned out, Jaypirca achieved a numerically higher overall response rate of 87.0% compared to 78.5% for Imbruvica in the study, which was also backed up by a trend towards improved progression-free survival (PFS) in both relapsed/refractory and treatment-naïve CLL/SLL populations. The PFS result in the untreated patients was particularly strong, according to the data, with a 6% reduction in the risk of disease progression or death.

The results of the 662-subject trial were presented at ASH and simultaneously published in the Journal of Clinical Oncology.

Jaypirca has been designed to work in patients who develop resistance mutations to covalent BTK inhibitors, and that profile has helped the drug make strong headway in the market, with global sales rising 76% to $143 million in the third quarter. Still, it has a long way to go to catch Imbruvica, which – while starting to decline – pulled in more than $700 million in the same period.

The recent approval in the second-line setting after prior treatment with a covalent BTK inhibitor – which came on the back of the BRUIN CLL-321 study – is expected to add further momentum to Jaypirca's growth as Lilly turns its attention to the treatment-naïve population.

"BRUIN CLL-314 is the first randomised study to compare covalent and non-covalent BTK inhibitors and to directly compare any BTK inhibitors in the treatment-naïve setting, offering findings that are important for advancing the field and patient care," said investigator Jennifer Woyach of Ohio State University Comprehensive Cancer Center.

"Pirtobrutinib was clearly non-inferior to ibrutinib, and the response rate actually favours pirtobrutinib in the total cohort," she added.

Meanwhile, subjects taking Jaypirca had lower rates of adverse event-related dose reductions, treatment discontinuation due to progressive disease, and certain cardiovascular side effects, including hypertension and the development of atrial fibrillation or flutter, which could make it an important option for older, frailer CLL/SLL patients.

Lilly also reported top-line results of another study – BRUIN CLL-313 – at ASH, which found significant improvements in PFS and a trend towards improved overall survival when Jaypirca was compared to standard chemoimmunotherapy (CIT) in previously untreated CLL/SLL.