Rhapsido (remibrutinib) for adult chronic spontaneous urticaria still active on H1 antihistamines

Dek: The FDA, Health Canada, the European Commission, and the UK MHRA have labelled an oral BTK inhibitor — 25 mg twice daily — for adults with chronic spontaneous urticaria that is still active on H1 antihistamines. Japan, Australia, and Switzerland have independent licences. China’s NMPA date is company until nmpa.gov.cn. Authorized is not funded. NICE is in progress, not a yes.

Access Level: Health Canada/FDA Approved
Canada zoom: Full NOC (not NOC/c). PM 2026-07-16, control 300491, DIN 02570076. DHPP Approved. First-sale / DPD Marketed unknown. SAP is the wrong door. CDA-AMC SR0940-000 Pending, not a recommendation. Provincial listing unknown.
Country or International: International (roster zoom: United States, Canada, European Union, United Kingdom, Japan, Australia, Switzerland. China: company until nmpa.gov.cn. Canada is a zoom, not the frame.)
Reader pillar: You or someone you love has chronic spontaneous urticaria that is still active on H1 antihistamines and needs a real path — a labelled twice-daily tablet where a regulator has authorised it, or a specialist conversation about who pays — not a headline.

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Rhapsido (remibrutinib; pronounced RAP-si-doe) is an oral Bruton’s tyrosine kinase (BTK) inhibitor. It is a 25 mg tablet taken twice daily. It is not an antihistamine and it is not a first-line replacement for H1 antihistamines. The labelled use in the United States and Canada is for adults with chronic spontaneous urticaria who remain symptomatic despite H1 antihistamine treatment.

The FDA approved it on 30 September 2025. Health Canada issued a Notice of Compliance on 16 July 2026 — a full NOC, not a Notice of Compliance with Conditions. The European Commission granted a centralised marketing authorisation on 23 April 2026. The UK MHRA authorised it on 5 August 2026. Japan’s PMDA listed ラプシド on 19 June 2026. Australia’s ARTG records a registration on 11 May 2026. Swissmedic authorised it on 19 June 2026 as add-on therapy.

This is not a cure. Itch and hives scores moved in two 12-week placebo-controlled trials. People still take a background H1 antihistamine on these labels. Other forms of urticaria are not on the US line.

Where this is taking place

REMIX-1 (NCT05030311 / CLOU064A2301) — Phase 3, COMPLETED (CT.gov verified April 2025; study completion 19 January 2024). Actual enrolment 470. Sponsor: Novartis Pharmaceuticals. 112 locations / 19 countries on CT.gov. No Canadian sites on that location list. Countries with listed sites include the United States, Argentina, Australia, Bulgaria, Colombia, Czechia, France, Hungary, India, Italy, Japan, Mexico, Puerto Rico, Russia, Singapore, South Korea, Spain, Taiwan, and Turkey. Not an enrolment path.

REMIX-2 (NCT05032157 / CLOU064A2302) — Phase 3, COMPLETED (verified April 2025; completion 5 January 2024). Actual enrolment 455. 122 locations / 18 countries. Canadian sites on CT.gov (historical): Edmonton, Alberta (T6G 1C3); Fredericton, New Brunswick (E3B 1G9); Kingston, Ontario (K7L 2V7); London, Ontario (N6H 5L5); Niagara Falls, Ontario (L2H 1H5); Ottawa, Ontario (K1G 6C6); Toronto, Ontario (M3B 3S6); Verdun, Quebec (H4G 3E7). Not an enrolment path.

FDA Snapshot: the two trials together contributed 912 adults at 237 sites in 18 countries, including the United States, Europe, Asia, Latin America, the Caribbean, Canada, and Japan (200 enrolled in the US; 712 outside).

NCT05513001 (CLOU064A2303B) — Phase 3b extension. ACTIVE_NOT_RECRUITING. Door: adults who already finished a preceding remibrutinib Phase 3 core study (REMIX-1, REMIX-2, or listed sister cores). Nine Canadian sites, including Calgary. Completers only. Not a first-script door.

Commercial supply (labelled CSU, adults, still on / inadequate response to H1 unless a local label says otherwise): United States, Canada (authorised; marketed flag unknown), European Union (EC MA), United Kingdom (MHRA), Japan (PMDA table), Australia (ARTG), Switzerland (Swissmedic). China: company NMPA until nmpa.gov.cn.

Approval matrix

Access by country

• United States: Allergist / dermatologist / immunologist. FDA-labelled 30 Sep 2025 for adults with CSU still symptomatic despite H1 antihistamines. One 25 mg tablet twice daily, with or without food. Swallow whole with water. Do not split, crush, or chew. Skip a missed dose. Hold 3–7 days around surgery. USPI does not mandate a REMS, specialty pharmacy, or routine labs. RHAPSIDO.com or 1-888-669-6682 (USPI / pregnancy registry). No copay dollars here. Prior authorization still applies. Not for other forms of urticaria. Not for children. Not a first-line antihistamine.
• Canada (zoom): Authorised (full NOC, 16 Jul 2026) and listed on DHPP as Approved, DIN 02570076. Adult CSU still symptomatic despite H1 antihistamines. Ask the CSU / allergy / dermatology clinic for a prescription. Authorized ≠ funded. CDA-AMC SR0940-000 is Pending — not a recommendation. pCPA and provincial / territorial / NIHB / RAMQ listing unknown. SAP is the wrong door for a labelled product. Novartis Canada medical information on the PM: 1-800-363-8883. Do not mail-order a US bottle as a substitute for a Canadian prescription. REMIX-2 Canadian sites are historical. The extension is completers only (9 Canadian sites including Calgary).
• European Union: EC marketing authorisation 23 April 2026. Adult CSU with inadequate response to H1. A physician experienced in CSU should start it. The SmPC tells prescribers to reassess and to consider stopping if there is no response after 24 weeks. Additional monitoring (inverted triangle). Member-state reimbursement unknown. Named-patient import is the wrong frame once a centralised MA exists; the remaining question is who pays in your country.
• United Kingdom: MHRA authorised 5 Aug 2026, PL 00101/1314. Same adult / inadequate-response-to-H1 line as the EMA SmPC, including consider stopping if no response after 24 weeks. NICE GID-TA11416 is in progress, expected 22 Oct 2026. Committee 13 Aug 2026 is not a TA. Not a yes. Do not assume NHS routine funding. Yellow Card: yellowcard.mhra.gov.uk.
• Japan: In-country commercial after MHLW 19 Jun 2026. PMDA table: chronic idiopathic urticaria with inadequate response to existing treatment. That sentence is not the North American H1 line. NHI unknown. Not a Canadian travel path.
• Australia: ARTG 485465 dated 11 May 2026. PI indication not in hand. Ask the specialist; PBS listing unknown.
• Switzerland: Swissmedic 19 Jun 2026, add-on to H1 for adult CSU still symptomatic. In-country specialist path. Not a Canadian travel path.
• China: In-country commercial only if NMPA has authorised — Novartis China says yes, 25 Nov 2025. nmpa.gov.cn was not retrieved. NRDL not found. Not a Canadian travel path.

If your regulator has not authorised it: do not import on your own. Travelling to a labelled market is a plan with both specialists, not a mail-order workaround.

Who is eligible (from the labels — they are not the same)

This is an adult CSU on H1 conversation. It is not a first-line antihistamine. It is not automatically for inducible urticaria, vasculitis, or other itch diseases.

United States (USPI):

• Adult.
• Chronic spontaneous urticaria.
• Still has symptoms despite H1 antihistamine treatment.
• Not indicated for other forms of urticaria.
• 25 mg twice daily with or without food, swallow whole.
• Avoid if you have any hepatic impairment (mild, moderate, or severe).
• Safety and effectiveness not established in children.

Canada (Product Monograph):

• Adult.
• CSU still symptomatic despite H1 antihistamine treatment.
• Pediatrics not authorised.
• Same 25 mg twice-daily swallow-whole, with or without food.
• Do not use if allergic to remibrutinib or a tablet ingredient.
• Hepatic: no dose change for mild or moderate; use with caution if moderate; avoid if severe.
• If you can become pregnant: effective contraception during treatment and for at least 1 week after the last dose. Do not breastfeed during treatment and for 1 week after.

European Union / United Kingdom (EPAR / SmPC):

• Adult.
• CSU with inadequate response to H1 antihistamine treatment.
• Started by a physician experienced in diagnosing and treating CSU.
• 25 mg morning and evening, with or without food.
• Prescriber should reassess; consider stopping if no response after 24 weeks.
• Hypersensitivity contraindication.
• Hepatic: not recommended in severe impairment; no adjustment for mild or moderate.
• Effective contraception during treatment and for ≥1 week after; not recommended in pregnancy; stop breastfeeding during treatment and for 1 week after.
• Should not be used in infants and children below 6 years (unknown effect on humoral-immunity maturation). Ages 6–18: safety and efficacy not established.

Switzerland (Swissmedic new-medicines page):

• Add-on therapy for adult CSU still symptomatic despite H1 antihistamines.

Japan (PMDA table, not the US label):

• Chronic idiopathic urticaria, limited to patients with inadequate response to existing treatment.
• Table row does not name H1. That sentence is not the Canadian or US label.

Not labelled:

• First-line antihistamine replacement / H1-naïve CSU.
• Other forms of urticaria on the US line (chronic inducible urticaria was an exclusion in REMIX).
• Children (US/Canada/EU 6–18 not established; EU also bars under 6).
• Relapsing multiple sclerosis, hidradenitis suppurativa, food allergy — not these CSU labels.

What the pivotal studies showed (use the label of the country that will prescribe)

REMIX-1 and REMIX-2 were identical 52-week trials: 24 weeks double-blind remibrutinib 25 mg twice daily versus placebo (2:1), then 28 weeks open-label. Everyone stayed on a background second-generation H1 antihistamine. Entry: CSU for ≥6 months, itch and hives for ≥6 consecutive weeks despite H1, UAS7 ≥16, ISS7 ≥6, HSS7 ≥6. About one-third had prior anti-IgE (mostly omalizumab).

USPI Table 3 — Week 12 (FDA co-primaries ISS7 and HSS7; UAS7 key secondary):

EMA/MHRA/HC treat UAS7 change at Week 12 as the primary scenario and report the same LS means. The 24-week stop-if-no-response sentence is on the EU/UK SmPC, not on the US Dosage section.

This is symptom-score improvement on background antihistamine, not a proven survival endpoint, and not a cure. About half reached well-controlled disease (UAS7 ≤6) at Week 12; about 30% had no itch and no hives that week.

How it is taken

Dose on US, Canadian, EU, and UK labels: 25 mg (one tablet) by mouth twice daily. Swallow whole with water. Do not split, crush, or chew. With or without food. If a dose is missed, skip it; do not double.

Surgery: interrupt 3 to 7 days before and after, depending on bleeding risk.

Hepatic — labels disagree:

• United States: avoid mild, moderate, and severe hepatic impairment.
• Canada: no adjustment for mild or moderate; caution in moderate; avoid severe.
• EU / UK: no adjustment for mild or moderate; not recommended in severe.

CYP3A4 — labels disagree:

• United States: avoid strong or moderate CYP3A4 inhibitors and inducers.
• Canada: caution with strong inhibitors; moderate inhibitors not expected to matter clinically; avoid strong or moderate inducers.
• EU / UK: avoid strong inhibitors; avoid moderate or strong inducers.

P-gp substrates with a narrow window (for example digoxin): monitor more often (all three labels). Anticoagulants were not allowed in the trials; low-dose aspirin (≤100 mg) or clopidogrel (≤75 mg) was allowed. Dual antiplatelet therapy was prohibited in the protocols.

Labs: the US, Canadian, and EU/UK dosage sections do not require routine laboratory monitoring. That is the label, not a copay card.

Safety (from the labels)

United States (Highlights / section 5):

• Risk of bleeding. Mucocutaneous bleeding 9% on Rhapsido vs 2% placebo in the 24-week pooled set (N=606 vs 306). Petechiae 4%, contusion 2%. No severe bleeding in that table. No link to low platelets. 0.5% discontinued for bleeding. Hold the drug if bleeding is seen; hold 3–7 days around surgery. Antithrombotics may add risk.
• Live / live-attenuated vaccines: avoid; no data.
• Most common adverse reactions (≥3% and more than placebo): nasopharyngitis 11% vs 9%; bleeding 9% vs 2%; headache 7% vs 6%; nausea 3% vs 2%; abdominal pain 3% vs 2%.
• Embryo-fetal: animal malformations in rabbits at 141×; human data insufficient. Pregnancy registry 1-888-669-6682.
• Contraindications: none.

Canada / EU / UK — extra lines the US Highlights do not carry:

• Hypersensitivity contraindication.
• Upper respiratory tract infections 14.7% vs 11.8% placebo on the Canadian ADR table (broader bucket than US “nasopharyngitis”).
• EU/UK: URTI very common; herpes virus infections common.
• Mandatory contraception for women of childbearing potential during treatment and for 1 week after; not recommended in pregnancy; stop breastfeeding during treatment and for 1 week after.
• EU/UK additional monitoring.

Bleeding was more often reported in women than men in the FDA Snapshot (11.4% vs 4.4% on drug).

Research team (Who)

Names below are as they appear on NCT, labels, the PMDA table, or the NEJM/JACI papers.

• Novartis Pharmaceuticals — trial sponsor; CT.gov Study Director (unnamed).
• Novartis Pharmaceuticals Corporation, East Hanover, NJ — US NDA holder / DailyMed packager.
• Novartis Pharmaceuticals Canada Inc., Montreal — Health Canada MAH; PM contact 1-800-363-8883.
• Novartis Europharm Limited, Dublin — EU MAH.
• Novartis Pharmaceuticals UK Limited — UK MAH, PL 00101/1314.
• ノバルティスファーマ株式会社 — Japan MAH (PMDA table).
• Novartis Pharmaceuticals Australia Pty Ltd — TGA ARTG sponsor.
• Novartis Pharma Schweiz AG — Swissmedic MAH, 70227.
• Martin Metz, M.D. and Marcus Maurer, M.D. — NEJM corresponding / equal contribution; Charité – Universitätsmedizin Berlin UCARE (NEJM byline).
• Ana Giménez-Arnau, M.D., Ph.D. — NEJM author; first author of the 52-week JACI paper.
• Gordon Sussman, M.D. — NEJM author, Division of Allergy and Clinical Immunology, University of Toronto (byline). Not listed as a CT.gov overall official.
• Julian Beach — MHRA Interim Executive Director of Healthcare Quality and Access, quoted on the 6 Aug 2026 GOV.UK news page.

No Canadian principal investigator is named on the REMIX CT.gov records. Facilities are “Novartis Investigative Site.”

How to talk to a doctor

Bring the NCT numbers and the label of the country you are in.

1. “I am an adult with chronic spontaneous urticaria that is still active on an H1 antihistamine. I am not asking to replace the antihistamine as first-line. Is Rhapsido (remibrutinib) 25 mg twice daily labelled for me here?”
2. “The US label says not for other forms of urticaria. Is mine CSU, or inducible / another diagnosis?”
3. “I take a blood thinner / I’m having surgery — the label says hold 3 to 7 days and watch for bruising, petechiae, nosebleeds, blood in urine or stool.”
4. “Live vaccines: the label says avoid while on this.”
5. Liver: “In the US, the label says avoid all hepatic impairment. In Canada / the EU, severe is the hard stop and moderate is caution / allowed. Which label are we using?”
6. “Which of my medicines are CYP3A4 inhibitors or inducers? The US label avoids moderate and strong inhibitors; Canada is caution on strong only.”
7. Pregnancy / breastfeeding / contraception for 1 week after the last dose (Canada/EU/UK). US pregnancy registry 1-888-669-6682.
8. Canada: “This is a full NOC, DIN 02570076. SAP is the wrong door. CDA-AMC SR0940 is pending, not a yes. What is actually funded in this province? I do not have a listing answer.”
9. UK: “MHRA yes; NICE GID-TA11416 is in progress, expected 22 October 2026, not a recommendation.”
10. EU: “EC licence yes. Who pays in this member state? The SmPC says consider stopping if nothing has changed by week 24.”

Canada zoom: authorised, not funded-by-default

Health Canada has already authorised Rhapsido with a full Notice of Compliance. That is not a compassionate-access story and it is not NOC/c. The remaining Canadian questions are who pays (CDA-AMC SR0940 pending; provinces unknown) and whether a first-sale / marketed flag is up (DHPP said Approved; first-sale unknown). Do not call the clinic asking for SAP. Do not assume a provincial formulary has listed it because a DIN exists.

Bottom line

Remibrutinib is a labelled oral BTK inhibitor for adults with chronic spontaneous urticaria still active on H1 antihistamines in the United States, Canada, the European Union, and the United Kingdom. Japan, Australia, and Switzerland have independent licences — Japan’s table is chronic idiopathic urticaria after existing treatment, and Switzerland’s line is add-on. China’s NMPA date stays company until nmpa.gov.cn. NICE is in progress, not a yes. Canada’s NOC is authorised, not a funding decision. SAP is the wrong door. REMIX-1 and REMIX-2 are completed. Authorized is not funded.

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Primary sources

1. DailyMed RHAPSIDO (setid e5e89bff-6ced-4165-acc5-fb13136b3a3d) — https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=e5e89bff-6ced-4165-acc5-fb13136b3a3d
2. FDA Drug Trials Snapshot: RHAPSIDO (approval date 30 Sep 2025) — https://www.fda.gov/drugs/drug-trials-snapshots/drug-trials-snapshot-rhapsido
3. FDA Novel Drug Approvals for 2025 (Rhapsido row, 9/30/2025) — https://www.fda.gov/drugs/novel-drug-approvals-fda/novel-drug-approvals-2025
4. EMA EPAR Rhapsido (EC MA 23 Apr 2026; CHMP opinion 26 Feb 2026) — https://www.ema.europa.eu/en/medicines/human/EPAR/rhapsido
5. EMA product information (SmPC) PDF — https://www.ema.europa.eu/en/documents/product-information/rhapsido-epar-product-information_en.pdf
6. EMA medicine overview PDF — https://www.ema.europa.eu/en/documents/overview/rhapsido-epar-medicine-overview_en.pdf
7. Health Canada Product Monograph (HRES 00085392; Date of Authorization 2026-07-16; control 300491) — https://pdf.hres.ca/dpd_pm/00085392.PDF
8. DHPP product page RHAPSIDO (DIN 02570076; resource 107225) — https://dhpp.hpfb-dgpsa.ca/dhpp/resource/107225
9. Register of Innovative Drugs (remibrutinib / Rhapsido NOC 2026-07-16) — https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/register-innovative-drugs.html
10. MHRA GOV.UK news (MA 5 Aug 2026; published 6 Aug 2026) — https://www.gov.uk/government/news/mhra-approves-remibrutinib-for-adults-with-chronic-spontaneous-urticaria
11. UK SmPC, emc product 102515 (PL 00101/1314; first authorisation 05/08/2026) — https://www.medicines.org.uk/emc/product/102515/smpc
12. NICE GID-TA11416 / ID6356 (in progress; expected 22 Oct 2026) — https://www.nice.org.uk/guidance/indevelopment/gid-ta11416
13. PMDA 承認品目一覧（新医薬品：2026年6月 / 8月 PDF, ラプシド 2026.6.19） — https://www.pmda.go.jp/files/000281577.pdf
14. Swissmedic new medicines: Rhapsido (70227; 19.06.2026) — https://www.swissmedic.ch/swissmedic/en/home/humanarzneimittel/authorisations/new-medicines/rhapsido-filmtabletten-remibrutinibum.html
15. TGA ARTG 485465 (11 May 2026) — https://www.tga.gov.au/resources/artg/485465
16. CDA-AMC remibrutinib SR0940-000 (pending) — https://www.cda-amc.ca/remibrutinib
17. ClinicalTrials.gov REMIX-1 NCT05030311 — https://clinicaltrials.gov/study/NCT05030311
18. ClinicalTrials.gov REMIX-2 NCT05032157 — https://clinicaltrials.gov/study/NCT05032157
19. ClinicalTrials.gov extension NCT05513001 — https://clinicaltrials.gov/study/NCT05513001
20. Metz M, Giménez-Arnau A, Hide M, et al. Remibrutinib in chronic spontaneous urticaria. N Engl J Med. 2025;392(10):984-994. DOI 10.1056/NEJMoa2408792 (journal; not the label)
21. Giménez-Arnau AM, Szalewski R, Hide M, et al. Remibrutinib in chronic spontaneous urticaria: 52-week results from two phase 3 studies. J Allergy Clin Immunol. 2026;157(1):143-154. DOI 10.1016/j.jaci.2025.09.028 (journal; not the label)
22. Novartis China company announcement, 25 Nov 2025 (company NMPA; not nmpa.gov.cn) — https://www.novartis.com.cn/news/nuohuamanxingzifaxingxunmazhencsuchuangxinyaowuruipuduoruimibutinipianzaihuahuopi-chengweiquanqiushougezhiliaomanxingzifaxingxunmazhencsudekoufubaxiangyaoweiqianwanzhongguohuanzhedailaichuangxinxuanze

Research team

Names and numbers below are only as they appear on the sources in the table.