Eli Lilly’s Jaypirca pushes into first-line CLL, but commercial upside may be limited
Jaypirca (pirtobrutinib) is Eli Lilly’s noncovalent BTK inhibitor, initially approved for relapsed or refractory CLL/SLL after at least two prior lines of therapy and has now received traditional (full) FDA approval for relapsed or refractory CLL/SLL previously treated with a covalent BTK inhibitor.24
The phase 3 Bruin-CLL-314 trial directly compared first-line or early-line Jaypirca with AbbVie/J&J’s Imbruvica (ibrutinib) in CLL/SLL, aiming to move Jaypirca earlier in the treatment sequence.16
In interim Bruin-CLL-314 data presented at the American Society of Hematology (ASH) 2025 meeting, Jaypirca achieved an 87% response rate versus 79% for Imbruvica across 662 participants, meeting the noninferiority goal and showing a statistically significant response advantage.16
Jaypirca reduced the relative risk of disease progression or death by 43% versus Imbruvica in the overall Bruin-CLL-314 population, with even greater benefit in treatment‑naïve patients compared with those previously treated.12
A separate phase 3 trial in treatment‑naïve CLL/SLL showed Jaypirca significantly improved progression‑free survival versus Imbruvica, reinforcing its potential as a first‑line option.26
Based on positive phase 3 data, Lilly has already sought a label expansion to include earlier‑line, treatment‑naïve CLL/SLL, aiming to establish Jaypirca as a front‑line or early‑line BTK backbone.15
Despite the strong first‑line efficacy data, Lilly’s oncology leadership has publicly indicated that Jaypirca’s commercial “sweet spot” is likely second‑line CLL—after covalent BTK inhibitors—rather than fully displacing entrenched first‑line options.3
One reason the revenue ceiling may be capped is that first‑line CLL is already crowded with highly effective regimens (including covalent BTK inhibitors and time‑limited venetoclax‑based combinations), making it difficult for Jaypirca to dominate initial therapy despite noninferiority or modest superiority to Imbruvica.13
Another limiting factor is strategic positioning:
Lilly can capitalize on a clearer unmet need in post‑BTK, second‑line CLL—where many patients fail or cannot tolerate covalent BTK inhibitors—rather than engaging in head‑to‑head competition for all first‑line patients.34
Jaypirca is also approved for relapsed or refractory mantle cell lymphoma, but Lilly’s current CLL focus is on consolidating its role after covalent BTK inhibitors while selectively expanding into earlier‑line use, which collectively shapes a meaningful but not blockbuster‑level market opportunity.23
Sources:
1. https://www.biopharmadive.com/news/ash-2025-lilly-jaypirca-imbruvica-leukemia-lymphoma/807232/
2. https://www.managedhealthcareexecutive.com/view/jaypirca-improves-survival-in-treatment-na-ve-cll-sll-patients-ash-2025
3. https://www.fiercepharma.com/pharma/lilly-oncology-chief-sees-jaypirca-sweet-spot-second-line-cll-despite-first-line-btk-trial
4. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-traditional-approval-pirtobrutinib-chronic-lymphocytic-leukemia-and-small-lymphocytic
5. https://www.clinicaltrialsarena.com/news/eli-lilly-results-jaypirca/
6. https://www.oncologynewscentral.com/cll/first-of-its-kind-phase-3-trial-shows-pirtobrutinib-is-noninferior-to-ibrutinib-in-treatment-naive-cll