Once-Daily Pill for Adults with Untreated CLL or SLL

Jaypirca is an oral kinase inhibitor (pirtobrutinib) that blocks Bruton tyrosine kinase (BTK), including BTK that has a C481 change. The United States prescribing information revised 10/2026 added a new use: adults with previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have no known 17p deletion. It is a 200 mg tablet once a day, swallowed whole, until the disease progresses or side effects are unacceptable. It is not chemotherapy by vein, not a cure, and not the same use as Jaypirca after a covalent BTK inhibitor or for mantle cell lymphoma. Marketed in the United States by Lilly USA, LLC.

Distinct path — not this use (fact-only): US indication 1.2 is relapsed or refractory CLL/SLL after a covalent BTK inhibitor. US indication 1.1 is relapsed or refractory mantle cell lymphoma after at least two lines of therapy including a BTK inhibitor, and that mantle-cell use is accelerated approval based on response rate. Those are different populations and different evidence. The October 2026 section (1.3) is only the previously untreated CLL/SLL use without a known 17p deletion.

Where this is taking place

Commercial door for this new US use: United States. Lilly USPI Revised 10/2026 (Recent Major Changes: Indications and Usage, Previously Untreated CLL/SLL with no known 17p deletion 1.3 — 10/2026; document code A6.0-JAY-0007-USPI-20261002). The FDA oncology approval page is dated 2 October 2026.

Who gives it: A hematology or oncology clinician who treats CLL/SLL, can confirm whether a 17p deletion is known, and can prescribe an oral anticancer tablet through the pharmacy channel already used for Jaypirca. Suspected side effects in the United States: FDA MedWatch 1-800-FDA-1088. The BRUIN CLL-313 record on ClinicalTrials.gov lists an Eli Lilly study-director line, 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559.

Trial that supported the new US section: BRUIN CLL-313 — NCT05023980 (Lilly study 20023). Phase 3, randomised, open-label, active-controlled. Sponsor on the trial record: Loxo Oncology, Inc. (Eli Lilly and Company). Status checked 3 October 2026: active, not recruiting. A trial site is not a marketing authorisation in that country.

European Union and United Kingdom: Jaypirca is already authorised there for adult CLL as monotherapy, including treatment-naïve CLL on the GB SmPC. The EU and UK indication sentences are not the same as US section 1.3. See the zoom below. Do not treat a US 17p rule as the EU rule, or the other way around.

Outside those labels: Health Canada, TGA, Swissmedic, and PMDA authorisation of Jaypirca for previously untreated CLL/SLL with no known 17p deletion is not confirmed on sources used here. Do not import on your own.

Approval matrix

Access by country

• United States: Ask hematology or oncology whether the person is an adult with CLL or SLL, has not been treated for it before, and has no known 17p deletion. Path: that conversation → blood counts and the infection, bleeding, heart, and liver checks the label describes → 200 mg by mouth once a day → ask the plan whether this indication is covered. No list price or copay dollars in this article.
• European Union / United Kingdom: A local cancer doctor can already consider Jaypirca under the local CLL SmPC. That label is not limited, in the indication sentence, to “no known 17p deletion,” and the GB text is written as CLL, not CLL/SLL. Use the local SmPC, not US section 1.3, for eligibility there.
• Canada / other countries: Authorisation not confirmed for this previously untreated 17p-restricted use on sources used here.
• If your regulator has not authorised it: do not import on your own.

Who is eligible

United States (prescribing information, indication 1.3, revised 10/2026):

• Indication: Treatment of adult patients with previously untreated chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) with no known 17p deletion.
• Not this section: People whose CLL/SLL has already been treated, including anyone whose next question is the after a covalent BTK inhibitor use (section 1.2). People with a known 17p deletion are outside section 1.3.
• Trial limits that shaped the evidence (BRUIN CLL-313 on the USPI): Platelets at least 75 × 10⁹/L, neutrophils at least 0.75 × 10⁹/L, estimated creatinine clearance at least 40 mL/min. The trial excluded significant cardiovascular disease (including uncontrolled or symptomatic arrhythmias), active uncontrolled autoimmune cytopenia, an active second malignancy, and 17p deletion. Those trial rules are not extra lines printed as contraindications. The USPI contraindications section says none.

Not established: The GB SmPC states that safety and efficacy in people under 18 have not been established. The US section 1.3 is written for adults.

What the pivotal study showed (BRUIN CLL-313 / NCT05023980)

USPI clinical studies, primary analysis. Randomised 1:1:

• Jaypirca 200 mg by mouth once daily until progression or unacceptable toxicity (141 people), or
• Bendamustine plus a rituximab product for up to 6 cycles (141 people). Bendamustine 90 mg/m² IV on days 1 and 2 of each 28-day cycle; rituximab product 375 mg/m² IV on day 1 of cycle 1, then 500 mg/m² on day 1 of later cycles.

After confirmed progression, people on bendamustine plus rituximab could cross over to Jaypirca. 18 of 141 in that arm did.

Randomisation was stratified by IGHV mutation status and Rai stage. Median age 66 years (range 29 to 88); 61% male; 73% White, 23% Asian, 0.4% Black or African American; 34% Rai stage III or IV; ECOG 0 or 1 in 94%; 57% unmutated IGHV; 10% complex karyotype.

Primary result (independent review, iwCLL 2018), estimated median follow-up 28 months:

• Progression or death events: 13 (9%) on Jaypirca vs 48 (34%) on bendamustine plus rituximab.
• Median progression-free survival: not estimable on Jaypirca vs 33.5 months (95% CI 32.7, not estimable) on bendamustine plus rituximab.
• Hazard ratio 0.20 (95% CI 0.11, 0.37); p <0.0001.

Overall response (complete + partial; no one had complete response with incomplete marrow recovery or nodular partial response as best response): 133/141 (94%) vs 114/141 (81%). Complete response 19 (13%) vs 29 (21%). Partial response 114 (81%) vs 85 (60%).

Overall survival was immature. At an estimated median follow-up of 32 months, median survival was not reached in either arm. Deaths: 3 (2.1%) on Jaypirca and 10 (7.1%) on bendamustine plus rituximab.

In the safety population described with this trial, 140 people received Jaypirca and 132 received bendamustine plus rituximab. Median time on Jaypirca was 32 months, with 92% still on it beyond 24 months.

How it is taken

United States prescribing information, section 2.1 (same 200 mg dose is used for the other US Jaypirca indications):

• 200 mg by mouth once daily until disease progression or unacceptable toxicity.
• Swallow tablets whole with water. Do not cut, crush, or chew.
• Same time each day, with or without food.
• If a dose is missed by more than 12 hours, skip it and take the next dose on schedule. Do not take an extra dose.
• Tablet strengths on the USPI: 50 mg and 100 mg.

Dose changes the USPI prints for problems or other medicines (not a home schedule):

• For specified severe blood-count or non-blood side effects, the label uses interrupt, then restart at 200 mg, then 100 mg, then 50 mg, then stop (section 2.2). Dose modification is not recommended for asymptomatic lymphocytosis.
• Severe kidney impairment (eGFR 15–29 mL/min): if the current dose is 200 mg once daily, reduce to 100 mg once daily (section 2.3). No adjustment is recommended for mild or moderate kidney impairment (eGFR 30–89).
• Avoid strong CYP3A inhibitors. If one cannot be avoided, reduce the Jaypirca dose by 50 mg (section 2.4).
• Avoid strong or moderate CYP3A inducers. If a moderate inducer cannot be avoided and the current dose is 200 mg, the label says increase to 300 mg (section 2.5).

The EU and GB SmPCs also state a recommended dose of 200 mg once daily. Interaction and dose-reduction tables are not worded the same as the USPI (the GB text says no dose adjustment is needed with CYP3A inhibitors, and advises avoiding strong CYP3A inducers if possible). Follow the label in the country where the prescription is written.

Safety (what the label puts first)

The 10/2026 USPI does not open with a boxed warning. Warnings and precautions start with infections.

Across clinical trials, in 1,153 people treated with Jaypirca, Grade 3 or higher infections occurred in 23%, most commonly pneumonia (13%), with fatal infections in 4.3%. In people with CLL/SLL, Grade 3 or higher infections occurred in 24%, with fatal infections in 5%. The label says to consider prophylaxis (including vaccines and antimicrobials) when infection risk is high, and to monitor, evaluate, and treat. Depending on severity, the dose may be reduced, held, or stopped.

Other warnings on the same USPI, in label order: serious or fatal bleeding (major hemorrhage in 3.1% of 1,153 people; the label says consider holding Jaypirca for 3 to 7 days before and after surgery); low blood counts (monitor complete blood counts); heart-rhythm problems, including atrial fibrillation and atrial flutter; second cancers, including skin cancer (sun protection and monitoring); liver injury, including drug-induced liver injury (monitor liver tests; abdominal discomfort, dark urine, or jaundice needs prompt contact with the prescriber); harm to a fetus.

In BRUIN CLL-313 specifically (USPI): serious adverse reactions in 28% of people on Jaypirca, including pneumonia in 5%. One fatal adverse reaction within 30 days of the last dose (0.7%), from septic shock. Permanent stop in 4.3%, dose reduction in 3.6%, interruption in 35%. Most common adverse reactions at or above 20%, excluding lab terms: upper respiratory tract infections 27%, rash 22%, COVID-19 21%. Neutrophil count decreased, all grades 48%, Grade 3 or 4 14%.

Pregnancy and feeding (US patient counseling): Jaypirca can cause fetal harm. Females of reproductive potential should use effective contraception during treatment and for one week after the last dose, and should not breastfeed during treatment and for one week after the last dose. The GB SmPC contraception intervals are longer (see zoom). Do not mix the two.

How to talk to a doctor

• Is this previously untreated CLL or SLL, or a later-line question (including after a covalent BTK inhibitor)?
• Is a 17p deletion known? US section 1.3 is only for no known 17p deletion.
• What infection risk, vaccine plan, and blood-count schedule does this label call for before and during treatment?
• Any bleeding history, blood thinners, or surgery coming up (the USPI discusses a 3-to-7-day hold around surgery)?
• Heart-rhythm history, liver tests, other cancers, pregnancy, and other medicines that are strong CYP3A inhibitors or moderate or strong CYP3A inducers?
• Will the plan cover this indication, not only an older Jaypirca use?

Research and regulatory team (from sources only — no invented contacts)

• US label holder / marketer: Lilly USA, LLC, Indianapolis, IN.
• FDA action: approval page dated 2 October 2026 for previously untreated CLL/SLL with no known 17p deletion; USPI revised 10/2026.
• BRUIN CLL-313 (NCT05023980): sponsor Loxo Oncology, Inc.; record organization Eli Lilly and Company. The named study-director field is the Lilly phone line above, not a physician name.
• EU marketing-authorisation holder on the EPAR: Eli Lilly Nederland B.V., Utrecht, Netherlands. EU authorisation is conditional.

EU zoom: adult CLL is already authorised, and the sentence is wider than the US

The EMA SmPC §4.1 authorises Jaypirca monotherapy for adult CLL. It does not add the US words “previously untreated,” “SLL,” or “no known 17p deletion” to that sentence. The EPAR overview describes benefit in people who had not been treated before, using the same bendamustine-plus-rituximab comparison (about 93% vs 71% alive without worsening at 24 months in that overview). Those 24-month percentages are not in the USPI efficacy table used above.

The GB SmPC §4.1 (revision 29 April 2026) is more explicit: treatment-naïve CLL, relapsed/refractory CLL never treated with a BTK inhibitor, and relapsed/refractory CLL after a BTK inhibitor. It still does not name SLL or a 17p exclusion in the indication.

GB SmPC §4.4 advises effective contraception for women of childbearing potential during treatment and for 5 weeks after the last dose, and for men during treatment and for 3 months after the last dose. US counseling cited above is one week for females and does not print that male interval.

MCL on both the US and EU labels remains a separate relapsed/refractory, post-BTK-inhibitor use.

Bottom line

Adults in the United States with previously untreated CLL or SLL and no known 17p deletion now have an FDA-approved once-daily oral option, Jaypirca 200 mg, supported by BRUIN CLL-313 (NCT05023980): fewer progression events than a fixed course of bendamustine plus rituximab, with overall survival still immature. The way in is a hematology or oncology prescription, not a trial slot and not an import. The EU and UK already authorise adult CLL more broadly; their indication text is not US section 1.3. This is not the after-BTK-inhibitor CLL use and not the mantle-cell use. Authorized is not funded.

Primary sources

• Lilly US prescribing information, Revised 10/2026 (indication 1.3; dosage 2.1–2.5; warnings 5.1–5.7; BRUIN CLL-313 safety and Table 13): pi.lilly.com/us/jaypirca-uspi.pdf
• FDA, 2 October 2026, approves pirtobrutinib for previously untreated CLL or SLL with no known 17p deletion: fda.gov approval page
• ClinicalTrials.gov NCT05023980 (BRUIN CLL-313): clinicaltrials.gov/study/NCT05023980
• EMA EPAR Jaypirca (authorised; product information last updated 15 September 2026) and SmPC §4.1: ema.europa.eu EPAR · product information PDF
• UK SmPC, Jaypirca 100 mg (emc; revision 29 April 2026): medicines.org.uk