Eli Lilly’s Jaypirca, the first noncovalent BTK inhibitor, has won FDA approval for the first-line treatment of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL).
Friday’s approval follows Jaypirca’s FDA approval in 2023 as a third-line therapy for CLL/SLL and a follow-on go-ahead in the second-line setting, making it the fourth BTK inhibitor cleared for previously untreated CLL/SLL.
Before Friday’s FDA green light, Jaypirca had already secured market authorization in the European Union across all lines of therapy.
“This milestone underscores Jaypirca’s versatility in the CLL continuum of care, from the first-line setting for appropriate patients to its valuable role in the relapsed or refractory post-covalent BTK inhibitor setting, reinforcing Jaypirca’s broad applicability as a meaningful treatment option for people with CLL or SLL,” Jacob Van Naarden, executive vice president and president of Lilly Oncology, said in a statement.
Jaypirca’s first-line label excludes patients whose tumors have known 17p deletion, consistent with the population included in the company’s phase 3 Bruin CLL-313 trial, which forms the basis of the latest approval.
Similarly, cohort 1 of the phase 3 Sequoia trial for BeOne Medicines’ Brukinsa, now the world’s top-selling BTK inhibitor, also excluded patients with known 17p deletion. Both trials set the criteria because their comparator therapy, bendamustine and rituximab (BR), is not suitable for del(17p) patients. BeOne made up for that gap with a single-arm exploratory analysis of Brukinsa in cohort 2 of Sequoia.
In Bruin CLL-313, Jaypirca significantly reduced the risk of progression or death by 80% compared with BR. The median progression-free survival time was not yet reached for Jaypirca at the time of the analysis, versus 33.5 months for BR.
Despite the positive first-line readout, Van Naarden, during a December interview with Fierce about the data, maintained that the primary use of Jaypirca “remains in second line.”
That’s because Jaypirca, as the only noncovalent, reversible BTK inhibitor, offers a unique option to treat patients who have received a covalent BTK inhibitor, including Brukinsa, AstraZeneca’s Calquence, and AbbVie and Johnson & Johnson’s older Imbruvica. The covalent BTK inhibitors themselves cannot be used sequentially. As a result, doctors are expected to save Jaypirca to preserve a treatment option for relapsed patients.
The National Comprehensive Cancer Network (NCCN) guidelines also encourage that strategy. Jaypirca now holds a category 2A recommendation in first-line CLL/SLL among older patients with cardiac comorbidities who may only need one lifetime treatment for CLL/SLL. By comparison, it's classified as a category 1 preferred option for CLL/SLL patients who have tried a covalent BTK inhibitor.
In addition to Bruin CLL-313, Jaypirca also showed a numerically higher overall response rate versus Imbruvica in a head-to-head fashion in the phase 3 Bruin CLL-314 trial conducted in CLL/SLL patients who were treatment-naïve or were new to a BTK drug.
In Bruin CLL-314, the Lilly drug also showed a lower rate of cardiovascular side effects versus Imbruvica.
Meanwhile, Lilly recently celebrated a positive phase 3 readout for a fixed-duration regimen of Jaypirca, venetoclax and rituximab in previously treated CLL/SLL. The Bruin CLL-322 trial showed that the time-limited Jaypirca regimen significantly improved PFS by 45.3% versus venetoclax and rituximab.
Jaypirca currently remains a relatively small product in Lilly’s obesity- and diabetes-heavy portfolio. The drug’s second-quarter sales jumped 56% year over year to $192 million, whereas Brukinsa generated global revenues of $1.2 billion during the same period after a 31% increase from the prior year.