Lilly's Jaypirca (pirtobrutinib) significantly reduced the risk of disease progression or death by 45% when added to a venetoclax time-limited regimen in people with previously treated CLL/SLL

Rhea-AI Summary

Lilly (NYSE: LLY) reported Phase 3 BRUIN CLL-322 results in relapsed or refractory CLL/SLL. Adding Jaypirca (pirtobrutinib) to venetoclax plus rituximab cut the risk of disease progression or death by 45% (HR=0.55; p=0.0001).

Among 639 patients (79.8% BTK-pretreated), median PFS was not reached with the triple regimen versus 39.7 months for control. Time to next treatment favored Jaypirca (HR=0.50). Overall survival data are immature. Safety was broadly consistent with known profiles, with similar Grade ≥3 AE and discontinuation rates.

Positive

• Jaypirca combo cut progression or death risk by 45% (HR=0.55; p=0.0001)
• Median PFS not reached with Jaypirca versus 39.7 months for control arm
• Second-line post-BTK subgroup HR=0.32 with 24-month PFS 88% vs 52%
• Time to next treatment favored Jaypirca regimen (HR=0.50; nominal p<0.0001)
• Grade ≥3 AE rates and discontinuation similar between Jaypirca and control arms
• Lilly plans global regulatory submissions to expand Jaypirca’s label

Negative

• Overall survival endpoint immature; HR=0.89 with wide 95% CI (0.57-1.40)
• High Grade ≥3 adverse event rates in both arms (78.8% vs 73.0%)
• Grade ≥3 neutropenia common with Jaypirca regimen (50.3% vs 43.7%)
• Atrial fibrillation/flutter, hypertension and hemorrhage observed with Jaypirca combination

Market Context

This announcement highlights strong Phase 3 BRUIN CLL‑322 data, with Jaypirca plus venetoclax/rituxi...

Analysis

This announcement highlights strong Phase 3 BRUIN CLL‑322 data, with Jaypirca plus venetoclax/rituximab reducing progression or death risk by 45% and improving key measures like PFS and time to next treatment. The largely BTK‑pretreated population supports relevance to current practice. In recent months, LLY has also reported important metabolic and dermatology milestones, underscoring a broad pipeline. Investors may focus on regulatory submissions, label expansion outcomes, and longer-term safety and survival follow-up for this regimen.

Key Figures

Risk reduction in PFS event: 45% reduction Hazard ratio for PFS: HR=0.55 (95% CI 0.40–0.75) Trial enrollment: 639 patients +5 more

8 metrics

Risk reduction in PFS event 45% reduction Jaypirca + venetoclax/rituximab vs venetoclax/rituximab in CLL/SLL

Hazard ratio for PFS HR=0.55 (95% CI 0.40–0.75) Primary endpoint, IRC-assessed PFS, p=0.0001

Trial enrollment 639 patients Relapsed/refractory CLL/SLL, BRUIN CLL-322

Prior BTK inhibitor exposure 79.8% of patients Participants with prior covalent BTK inhibitor

Median follow-up 27.3 months Data cutoff Feb. 2, 2026 for PFS analysis

Median PFS control arm 39.7 months Venetoclax + rituximab (VR) arm, 95% CI 35.9–NE

Second-line PFS hazard ratio HR=0.32 (95% CI 0.14–0.73) Exploratory second-line subgroup after first-line BTK inhibitor

24-month PFS rates 88% vs 52% PVR vs VR in second-line exploratory subgroup

Historical Context

5 past events · Latest: Jun 10 (Positive)

Pattern 5 events

Date	Event	Sentiment	24h Move	Catalyst
Jun 10	OSA campaign launch	Positive	-0.7%	National Zepbound OSA awareness campaign with Shaquille O’Neal.
Jun 09	EBGLYSS dosing approval	Positive	-0.7%	FDA approval of every-eight-week EBGLYSS maintenance regimen.
Jun 09	Global health partnership	Positive	-0.7%	Lilly Foundation and Convatec commit about $5M to Partners In Health.
Jun 08	Foundayo Phase 3 data	Positive	+2.5%	Phase 3 ACHIEVE trials show superior A1C and weight loss for Foundayo.
Jun 07	Foundayo menopause analysis	Positive	+2.5%	Post-hoc data show significant Foundayo weight loss across menopause stages.

24h Move is the share-price change in the day after each event; other market factors may also have contributed.

Pattern Detected

Recent positive clinical and regulatory news has produced mixed reactions, with several instances of negative or flat price moves on ostensibly favorable updates.

Recent Company History

Over the past week, LLY released multiple positive updates, including FDA approval for EBGLYSS dosing on Jun 9 and strong Phase 3 data for oral GLP‑1 Foundayo on Jun 8. Those metabolic and dermatology catalysts saw both aligned (+2.55%) and divergent (-0.73%) price reactions. The current Jaypirca CLL/SLL Phase 3 result adds another efficacy milestone in oncology, extending a pattern of clinically important, label-expanding data across several franchises.

Key Terms

phase 3, progression-free survival, overall survival, bruton tyrosine kinase, +4 more

8 terms

phase 3 medical

"BRUIN CLL-322 is the first Phase 3 study to demonstrate superiority"

Phase 3 is the late-stage clinical testing step for a new drug or medical treatment, where the product is given to large groups of patients to confirm effectiveness, monitor side effects, and compare it to standard care. Successful Phase 3 results are often the final scientific hurdle before regulators decide on approval and market launch—like passing a final exam before graduation—and can sharply change a company's valuation and future revenue prospects.

progression-free survival medical

"met its primary endpoint of ... progression-free survival (PFS)"

Progression-free survival is the length of time during and after a treatment that a patient's disease does not get worse, measured from the start of treatment until the disease shows measurable signs of progression or the patient dies. Investors care because longer progression-free survival in clinical trials often signals that a drug is effective, improving chances of regulatory approval, market adoption, and revenue potential—think of it as a stopwatch showing how long a therapy can keep the illness at bay.

overall survival medical

"Overall survival (OS), a key secondary endpoint, was not yet mature"

Overall survival is the average or median length of time patients remain alive after starting a treatment or entering a clinical study, measured regardless of cause of death. Investors care because it is a clear, hard measure of a therapy’s real-world benefit — like timing how long a new battery actually runs — and strong improvements in overall survival can drive regulatory approval, market adoption and revenue potential.

bruton tyrosine kinase medical

"Jaypirca (pirtobrutinib), a non-covalent Bruton tyrosine kinase (BTK) inhibitor"

Bruton tyrosine kinase (BTK) is a protein inside certain immune cells that acts like a control switch, helping those cells receive signals that tell them to grow, divide, or produce antibodies. It matters to investors because medicines that block or modify BTK can treat blood cancers and autoimmune diseases, so clinical results, regulatory decisions, or patent news about BTK-targeting drugs can materially affect the value of companies developing those therapies.

relapsed or refractory medical

"in patients with relapsed or refractory chronic lymphocytic leukemia"

"Relapsed or refractory" describes a situation where a disease, such as an illness or condition, returns after treatment or does not respond to initial treatment efforts. For investors, this indicates ongoing challenges or setbacks in managing the disease, which can affect the success of related treatments or therapies and impact the potential value of associated companies or products. Understanding this helps gauge the stability and future prospects of medical developments or healthcare investments.

tumor lysis syndrome medical

"Grade ≥3 clinical AEs of interest included neutropenia ... and tumor lysis syndrome"

A rapid, dangerous breakdown of large numbers of cancer cells that releases their contents into the bloodstream, causing sudden chemical imbalances that can damage the kidneys, heart and other organs. It matters to investors because it can affect the safety profile of cancer treatments, trigger trial pauses, change regulatory decisions, and influence market value—think of it like a sudden toxic spill after a dam breaks that forces emergency action and reassessment of a product’s risk.

time to next treatment medical

"An additional secondary endpoint, time to next treatment (TTNT), consistently favored"

Time to next treatment measures how long a patient goes after a given therapy before needing another systemic treatment. For investors, it signals how durable and practical a therapy’s benefit is—longer intervals suggest patients stay well enough that doctors delay additional treatment, which can imply better effectiveness, fewer side effects, or lower ongoing costs. Think of it like how long a product’s performance lasts before a replacement is needed.

independent review committee medical

"met its primary endpoint of independent review committee (IRC)-assessed PFS"

A group of independent experts who review proposed transactions, conflicts, or important decisions to ensure they are fair, compliant and in the best interest of shareholders. Think of them as an impartial referee or neighborhood oversight panel: they provide an outside check that reduces the risk of biased deals, increases transparency, and helps investors trust that management’s actions won’t unfairly benefit insiders or hidden parties.

AI-generated analysis. How Rhea-AI works. Not financial advice.

See more from StockTitan in Google Search and AI answers. Adds StockTitan as a preferred source · opens Google

Add on Google Not now

BRUIN CLL-322 is the first Phase 3 study to demonstrate superiority over a venetoclax-containing control arm in CLL, and, with the majority of patients previously treated with a covalent BTK inhibitor, reflects current practice patterns

These data will be highlighted in a late-breaking oral presentation at the 2026 European Hematology Association (EHA) Annual Meeting

INDIANAPOLIS, June 14, 2026 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) today announced results from the Phase 3 BRUIN CLL-322 clinical trial of Jaypirca (pirtobrutinib), a non-covalent Bruton tyrosine kinase (BTK) inhibitor, plus venetoclax and rituximab versus venetoclax and rituximab in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL). The study met its primary endpoint of independent review committee (IRC)-assessed progression-free survival (PFS), demonstrating that the addition of pirtobrutinib to a two-year venetoclax plus rituximab regimen reduced the risk of disease progression or death by 45% (HR=0.55 [95% CI, 0.40-0.75]; p=0.0001).

These data will be highlighted in a late-breaking oral presentation at the 2026 European Hematology Association (EHA) Annual Meeting taking place in Stockholm, Sweden, as well as featured in the meeting's press program.

"These results from BRUIN CLL-322 show that the addition of pirtobrutinib as part of a time-limited regimen further enhanced an already effective treatment and extended the duration of remission for patients with previously treated CLL. Importantly, the study provides the first robust evidence for such an approach in patients who received a prior BTK inhibitor," said Matthew S. Davids, M.D., M.M.Sc., Chief of the Division of Lymphoma at Dana-Farber Cancer Institute, who is the lead author on the study. "Time-limited regimens are an important option in CLL care and provide patients with meaningful treatment-free intervals. In the context of the modern CLL treatment landscape, where many patients may only receive two lines of therapy, these results speak to the potential benefits that improving second-line therapy can have. Our study has the potential to establish a new standard of care in this population."

BRUIN CLL-322 enrolled 639 relapsed or refractory patients, with 79.8% having prior covalent BTK inhibitor exposure, who were randomized 1:1 to receive pirtobrutinib plus venetoclax and rituximab (PVR, n=321) or venetoclax and rituximab alone (VR, n=318). Patients in the PVR arm received three cycles of pirtobrutinib and the first three cycles of rituximab before venetoclax was introduced. The efficacy results are based on a Feb. 2, 2026 data cutoff. At a median follow-up of 27.3 months, the primary endpoint of IRC-assessed PFS was significantly improved with the addition of pirtobrutinib to VR compared to VR alone (HR=0.55 [95% CI, 0.40-0.75]; p=0.0001). Median PFS in the PVR arm was not reached (95% CI, 43.3-NE), versus 39.7 months (95% CI, 35.9-NE) in the VR arm. The PFS results were consistent across prespecified subgroups, including patients with prior covalent BTK inhibitor exposure (PVR: not reached [95% CI, 41.5-NE] versus VR: 36.2 months [95% CI, 33.2-NE]), those who discontinued prior covalent BTK inhibitor due to progressive disease (PVR: 43.3 months [95% CI, 39.2-NE] versus VR: 33.2 months [95% CI, 28.3-37.5]), as well as those with high-risk features such as unmutated IGHV, TP53 mutation and/or 17p deletion, and/or complex karyotype. In an exploratory analysis of second-line patients whose disease progressed after a first-line covalent BTK inhibitor, the median PFS was not reached (95% CI, 30.1-NE) in the PVR arm and was 28.3 months (95% CI, 20.5-NE) in the VR arm (HR=0.32 [95% CI, 0.14-0.73]), with 24-month PFS rates of 88% (95% CI, 75.7-94.6) and 52% (95% CI, 34.7-66.2), respectively, and consistent benefit was observed regardless of the specific prior covalent BTK inhibitor received.

Overall survival (OS), a key secondary endpoint, was not yet mature at this analysis (HR=0.89 [95% CI, 0.57-1.40]), and final testing of OS superiority is planned at a future date. An additional secondary endpoint, time to next treatment (TTNT), consistently favored the pirtobrutinib combination regimen (HR=0.50 [95% CI, 0.35-0.70]; nominal p<0.0001).

The overall safety profile of this regimen in BRUIN CLL-322 was consistent with the known safety profile of each medicine, with little additive toxicity observed with the addition of pirtobrutinib to venetoclax and rituximab. Rates of Grade ≥3 adverse events (AEs) were similar with PVR compared to VR (78.8% versus 73.0%, respectively). Low rates of any grade atrial fibrillation/flutter (3.5% versus 2.6%, respectively), hypertension (12.0% versus 7.4%, respectively), and hemorrhage (14.2% versus 10.6%, respectively) were seen with PVR versus VR. Grade ≥3 clinical AEs of interest included neutropenia (50.3% versus 43.7%, respectively) and tumor lysis syndrome (0.9% versus 3.9%, respectively) in the PVR and VR arms. Discontinuation rates due to treatment-related AEs were similar across the PVR and VR study arms (5.4% versus 5.1%, respectively). The addition of pirtobrutinib to VR also allowed for downgrading of tumor lysis risk, with 78% of high-risk patients downgraded to medium (n=20) or low risk (n=18), and 61% of medium-risk patients downgraded to low risk.

"These remarkable findings support the potential addition of two years of Jaypirca to a time-limited venetoclax-based regimen in relapsed or refractory CLL," said Jacob Van Naarden, executive vice president and president of Lilly Oncology. "BRUIN CLL-322 enrolled a mostly covalent BTK inhibitor-pretreated population, ensuring that these results have applicability to the modern CLL treatment landscape where covalent BTK inhibitor use is now common. Additionally, these data further strengthen the unique body of evidence for Jaypirca across the CLL continuum, from monotherapy to combination therapy and across multiple settings where CLL patients need effective treatment."

Lilly plans to submit results from the BRUIN CLL-322 study to global regulatory authorities with the goal of further expanding Jaypirca's label.

Lilly is studying Jaypirca in CLL/SLL in multiple Phase 3 studies. Details on the trials can be found by visiting clinicaltrials.gov.

About BRUIN CLL-322
BRUIN CLL-322 is a global, randomized, open-label, Phase 3 study comparing time-limited pirtobrutinib plus venetoclax and rituximab versus venetoclax and rituximab in previously treated CLL/SLL patients. The trial enrolled 639 patients, who were randomized 1:1 to receive pirtobrutinib (200 mg, once daily) plus venetoclax and rituximab per their labeled doses or venetoclax and rituximab alone. The primary endpoint is PFS as assessed by blinded IRC. Secondary endpoints include PFS as assessed by investigator, OS, TTNT, event-free survival, overall response rate, time to worsening of CLL/SLL-related symptoms, time to worsening of physical functioning, safety and tolerability.

About Jaypirca (pirtobrutinib) 
Jaypirca (pirtobrutinib) (pronounced jay-pihr-kaa) is a highly selective (300 times more selective for BTK versus 98% of other kinases tested in preclinical studies), non-covalent inhibitor of the enzyme BTK.¹ BTK is a validated molecular target found across numerous B-cell leukemias and lymphomas including mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL).^2,3 Jaypirca is a U.S. FDA-approved oral prescription medicine, 100 mg or 50 mg tablets taken as a once-daily 200 mg dose with or without food until disease progression or unacceptable toxicity.

INDICATIONS FOR JAYPIRCA (pirtobrutinib)
Jaypirca is indicated for the treatment of

• Adult patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have previously been treated with a covalent BTK inhibitor.
• Adult patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK inhibitor. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

IMPORTANT SAFETY INFORMATION FOR JAYPIRCA (pirtobrutinib)

Infections: Fatal and serious infections (including bacterial, viral, fungal) and opportunistic infections occurred in Jaypirca-treated patients. Across clinical trials, Grade ≥3 infections occurred (25%), most commonly pneumonia (20%); fatal infections (5%), sepsis (6%), and febrile neutropenia (3.8%) occurred. In patients with CLL/SLL, Grade ≥3 infections occurred (32%), with fatal infections occurring in 8%. Opportunistic infections included Pneumocystis jirovecii pneumonia and fungal infection. Consider prophylaxis, including vaccinations and antimicrobial prophylaxis, in patients at increased risk for infection, including opportunistic infections. Monitor for signs and symptoms, evaluate, and treat. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

Hemorrhage: Fatal and serious hemorrhage has occurred with Jaypirca. Across clinical trials, major hemorrhage (Grade ≥3 bleeding or any central nervous system bleeding) occurred (2.6%), including gastrointestinal hemorrhage; fatal hemorrhage occurred (0.3%). Bleeding of any grade, excluding bruising and petechiae, occurred (16%). Major hemorrhage occurred when taking Jaypirca with (2.0%) and without (0.6%) antithrombotic agents. Consider risks/benefits of co-administering antithrombotic agents with Jaypirca. Monitor for signs of bleeding. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca. Consider withholding Jaypirca 3-7 days pre- and post-surgery based on surgery type and bleeding risk.

Cytopenias: Jaypirca can cause cytopenias, including neutropenia, thrombocytopenia, and anemia. Across clinical trials, Grade 3 or 4 cytopenias, including decreased neutrophils (27%), decreased platelets (13%), and decreased hemoglobin (11%), developed. Grade 4 decreased neutrophils (15%) and Grade 4 decreased platelets (6%) developed. Monitor complete blood counts regularly. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

Cardiac Arrhythmias: Cardiac arrhythmias occurred in patients taking Jaypirca. Across clinical trials, atrial fibrillation or flutter were reported in 3.4% of Jaypirca treated patients, with Grade 3 or 4 atrial fibrillation or flutter in 1.6%. Other serious cardiac arrhythmias such as supraventricular tachycardia and cardiac arrest occurred (0.4%). Cardiac risk factors such as hypertension or previous arrhythmias may increase risk. Monitor and manage signs and symptoms of arrhythmias (e.g., palpitations, dizziness, syncope, dyspnea). Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

Second Primary Malignancies: Across clinical trials, second primary malignancies, including non-skin carcinomas, developed in 9% of Jaypirca-treated patients, most frequently non-melanoma skin cancer (4.4%). Other second primary malignancies included solid tumors (including genitourinary and breast cancers) and melanoma. Advise patients to use sun protection and monitor for development of second primary malignancies.

Hepatotoxicity, Including Drug-Induced Liver Injury (DILI): Hepatotoxicity, including severe, life-threatening, and potentially fatal cases of DILI, has occurred in patients treated with BTK inhibitors, including Jaypirca. Evaluate bilirubin and transaminases at baseline and throughout Jaypirca treatment. For patients who develop abnormal liver tests after Jaypirca, monitor more frequently for liver test abnormalities and clinical signs and symptoms of hepatic toxicity. If DILI is suspected, withhold Jaypirca. If DILI is confirmed, discontinue Jaypirca.

Embryo-Fetal Toxicity: Jaypirca can cause fetal harm. Administration of pirtobrutinib to pregnant rats caused embryo-fetal toxicity, including embryo-fetal mortality and malformations at maternal exposures (AUC) approximately 3-times the recommended 200 mg/day dose. Advise pregnant women of fetal risk and females of reproductive potential to use effective contraception during treatment and for one week after last dose.

Adverse Reactions (ARs) in Patients Who Received Jaypirca

The most common (≥30%) ARs in the pooled safety population of patients with hematologic malignancies (n=704) were decreased neutrophil count (54%), decreased hemoglobin (43%), decreased leukocytes (32%), fatigue (31%), decreased platelets (31%), decreased lymphocyte count (31%), calcium decreased (30%).

Mantle Cell Lymphoma

Serious ARs occurred in 38% of patients, with pneumonia (14%), COVID-19 (4.7%), musculoskeletal pain (3.9%), hemorrhage (2.3%), pleural effusion (2.3%), and sepsis (2.3%) occurring in ≥2% of patients. Fatal ARs within 28 days of last dose occurred in 7% of patients, most commonly due to infections (4.7%), including COVID-19 (3.1% of all patients).

Dose Modifications and Discontinuations Due to ARs: Dose reductions in 4.7%, treatment interruption in 32%, and permanent discontinuation of Jaypirca in 9% of patients. Permanent discontinuation in >1% of patients included pneumonia.

Most common ARs (≥15%) and Select Laboratory Abnormalities (≥10%) (all Grades %; Grade 3-4 %): hemoglobin decreased (42; 9), platelet count decreased (39; 14), neutrophil count decreased (36; 16), lymphocyte count decreased (32; 15), creatinine increased (30; 1.6), fatigue (29; 1.6), musculoskeletal pain (27; 3.9), calcium decreased (19; 1.6), diarrhea (19; -), edema (18; 0.8), dyspnea (17; 2.3), AST increased (17; 1.6), pneumonia (16; 14), bruising (16; -), potassium decreased (13; 1.6), sodium decreased (13; -), lipase increased (12; 4.4), ALT increased (11; 1.6), potassium increased (11; 0.8), alkaline phosphatase increased (11; -). Grade 4 laboratory abnormalities in >5% of patients included neutrophils decreased (10), platelets decreased (7), lymphocytes decreased (6).

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma from Single-Arm and Randomized Controlled Clinical Trials

Serious ARs occurred in 47-56% of patients across clinical trials. Serious ARs in ≥5% of patients in the single-arm trial were pneumonia (18%), COVID-19 (9%), sepsis (7%), febrile neutropenia (7%). Serious ARs in ≥3% of patients in the randomized controlled trial were pneumonia (21%), COVID-19 (5%), sepsis (3.4%). Fatal ARs within 28-30 days of last Jaypirca dose occurred in 8-11% of patients, most commonly due to infections (7-10%), including sepsis (5%), COVID-19 (2.7-5%), and pneumonia (3.4%).

Dose Modifications and Discontinuations Due to ARs: Dose reductions in 3.6-10%, treatment interruption in 42-51%, and permanent discontinuation of Jaypirca in 9-17% of patients. Permanent discontinuation in >1% of patients included second primary malignancy, pneumonia, COVID-19, neutropenia, sepsis, anemia, and cardiac arrhythmias.

Most common ARs and Select Laboratory Abnormalities (≥20%) (all Grades %, Grade 3-4 %)--in a randomized controlled trial: neutrophil count decreased (54; 26), hemoglobin decreased (45; 10), platelet count decreased (37; 17), pneumonia (28; 16), ALT increased (25; 1.8), creatinine increased (25; -), calcium decreased (23; 0.9), sodium decreased (22; 0.9), bilirubin increased (21; 0.9), upper respiratory tract infections (21; 0.9); in a single-arm trial: neutrophil count decreased (63; 45), hemoglobin decreased (48; 19), calcium decreased (40; 2.8), fatigue (36; 2.7), bruising (36; -), cough (33; -), musculoskeletal pain (32; 0.9), platelet count decreased (30; 15), sodium decreased (30; -), COVID-19 (28; 7), pneumonia (27; 16), diarrhea (26; -), abdominal pain (25; 2.7), lymphocyte count decreased (23; 8), ALT increased (23; 2.8), AST increased (23; 1.9), creatinine increased (23; -), dyspnea (22; 2.7), hemorrhage (22; 2.7), lipase increased (21; 7), alkaline phosphatase increased (21; -), edema (21; -), nausea (21; -), pyrexia (20; 2.7), headache (20; 0.9). Grade 4 laboratory abnormalities in >5% of patients included neutrophils decreased (23).

Drug Interactions

Strong CYP3A Inhibitors: Concomitant use increased pirtobrutinib systemic exposure, which may increase risk of Jaypirca ARs. Avoid using strong CYP3A inhibitors with Jaypirca. If concomitant use is unavoidable, reduce Jaypirca dose according to approved labeling.

Strong or Moderate CYP3A Inducers: Concomitant use decreased pirtobrutinib systemic exposure, which may reduce Jaypirca efficacy. Avoid using Jaypirca with strong or moderate CYP3A inducers. If concomitant use with moderate CYP3A inducers is unavoidable, increase Jaypirca dose according to approved labeling.

Sensitive CYP2C8, CYP2C19, CYP3A, P-gp, or BCRP Substrates: Use with Jaypirca increased their plasma concentrations, which may increase risk of ARs related to these substrates for drugs sensitive to minimal concentration changes. Follow recommendations for these sensitive substrates in their approved labeling.

Use in Specific Populations

Pregnancy and Lactation: Due to potential for Jaypirca to cause fetal harm, verify pregnancy status in females of reproductive potential prior to starting Jaypirca. Presence of pirtobrutinib in human milk is unknown. Advise women to use effective contraception and to not breastfeed while taking Jaypirca and for one week after last dose.

Geriatric Use: In the pooled safety population of patients with hematologic malignancies, patients aged ≥65 years experienced higher rates of Grade ≥3 ARs and serious ARs compared to patients <65 years of age.

Renal Impairment: Because severe renal impairment increases pirtobrutinib exposure, reduce Jaypirca dose in these patients according to approved labeling.

PT HCP ISI MCL_CLL Q42025

Please see Prescribing Information and Patient Information for Jaypirca.

About Lilly                                        
Lilly is a medicine company turning science into healing to make life better for people around the world. We've been pioneering life-changing discoveries for 150 years, and today our medicines help tens of millions of people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges: redefining diabetes care; treating obesity and curtailing its most devastating long-term effects; advancing the fight against Alzheimer's disease; providing solutions to some of the most debilitating immune system disorders; and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we're motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. To learn more, visit Lilly.com and Lilly.com/news, or follow us on Facebook, Instagram, and LinkedIn. P-LLY

© Lilly USA, LLC 2026. ALL RIGHTS RESERVED.

Trademarks and Trade Names
All trademarks or trade names referred to in this press release are the property of the company, or, to the extent trademarks or trade names belonging to other companies are referenced in this press release, the property of their respective owners. Solely for convenience, the trademarks and trade names in this press release are referred to without the ^® and ™ symbols, but such references should not be construed as any indicator that the company or, to the extent applicable, their respective owners will not assert, to the fullest extent under applicable law, the company's or their rights thereto. We do not intend the use or display of other companies' trademarks and trade names to imply a relationship with, or endorsement or sponsorship of us by, any other companies.

Cautionary Statement Regarding Forward-Looking Statements
This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about Jaypirca (pirtobrutinib), as a potential treatment for adults with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL), and the timeline for future regulatory submissions, presentations, and other milestones relating to Jaypirca and its clinical trials, and reflects Lilly's current beliefs and expectations. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of drug research, development, and commercialization. Among other things, there is no guarantee that planned or ongoing studies will be completed as planned, that future study results will be consistent with study results to date, or that Jaypirca will receive additional regulatory approvals. For further discussion of these and other risks and uncertainties that could cause actual results to differ from Lilly's expectations, see Lilly's Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this release.

Endnotes & References

1. Mato AR, Shah NN, Jurczak W, et al. Pirtobrutinib in relapsed or refractory B-cell malignancies (BRUIN): a phase 1/2 study. Lancet. 2021;397(10277):892-901. doi:10.1016/S0140-6736(21)00224-5
2. Hanel W, Epperla N. Emerging therapies in mantle cell lymphoma. J Hematol Oncol. 2020;13(1):79. Published 2020 Jun 17. doi:10.1186/s13045-020-00914-1
3. Gu D, Tang H, Wu J, Li J, Miao Y. Targeting Bruton tyrosine kinase using non-covalent inhibitors in B cell malignancies. J Hematol Oncol. 2021;14(1):40. Published 2021 Mar 6. doi:10.1186/s13045-021-01049-7

Refer to:	Kyle Owens; Owens_Kyle@lilly.com (Media)
	Michael Czapar; czapar_michael_c@lilly.com (Investors)

View original content to download multimedia:https://www.prnewswire.com/news-releases/lillys-jaypirca-pirtobrutinib-significantly-reduced-the-risk-of-disease-progression-or-death-by-45-when-added-to-a-venetoclax-time-limited-regimen-in-people-with-previously-treated-cllsll-302799348.html

SOURCE Eli Lilly and Company

FAQ

What did Lilly (LLY) announce about the Jaypirca BRUIN CLL-322 Phase 3 trial?

Lilly announced that the Phase 3 BRUIN CLL-322 trial met its primary endpoint in relapsed or refractory CLL/SLL. According to Lilly, adding Jaypirca to venetoclax and rituximab reduced the risk of disease progression or death by 45% versus control.

How much did Jaypirca reduce progression risk in Lilly’s BRUIN CLL-322 study for CLL/SLL?

Jaypirca cut the risk of disease progression or death by 45% when added to venetoclax plus rituximab. According to Lilly, the hazard ratio for progression-free survival was 0.55 (95% CI, 0.40-0.75; p=0.0001), with consistent benefit across key prespecified subgroups.

What were the key progression-free survival results in Lilly’s Jaypirca BRUIN CLL-322 trial?

The Jaypirca combination significantly improved progression-free survival versus venetoclax plus rituximab alone. According to Lilly, median PFS was not reached with Jaypirca versus 39.7 months in the control arm after 27.3 months’ median follow-up, with consistent effects in high-risk and BTK-pretreated patients.

How did safety of Jaypirca plus venetoclax and rituximab compare in the BRUIN CLL-322 trial?

Safety with Jaypirca plus venetoclax and rituximab was generally consistent with known profiles of each drug. According to Lilly, Grade ≥3 adverse events occurred in 78.8% vs 73.0%, with similar treatment-related discontinuation rates (5.4% vs 5.1%) between combination and control arms.

What are Lilly’s next steps for Jaypirca (LLY) after the BRUIN CLL-322 CLL/SLL results?

Lilly plans to use the BRUIN CLL-322 data to pursue regulatory expansion for Jaypirca. According to Lilly, results will be submitted to global regulatory authorities, and Jaypirca continues to be studied in multiple Phase 3 CLL/SLL trials listed on clinicaltrials.gov.

Did Lilly’s Jaypirca BRUIN CLL-322 trial show an overall survival benefit in CLL/SLL?

Overall survival benefit has not yet been demonstrated in the BRUIN CLL-322 analysis. According to Lilly, the overall survival hazard ratio was 0.89 (95% CI, 0.57-1.40) and remains immature, with final testing of superiority planned at a later date.