New Pill for Chronic Hives Not Controlled by Antihistamines

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 Canada is for adults with chronic spontaneous urticaria (CSU) who remain symptomatic despite H1 antihistamine treatment. The US label (revised October 2026, section 1) covers adult patients who "remain symptomatic despite use of H1 antihistamine". It lists two uses: chronic spontaneous urticaria and symptomatic dermographism.

• Symptomatic dermographism: a form of chronic inducible urticaria (the trial record's grouping) in which hives appear where the skin is rubbed or scratched.

The FDA approved it on 30 September 2025 for chronic spontaneous urticaria. It added symptomatic dermographism on 6 October 2026 (New Drug Application 218436, supplement 1). 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 Medicines and Healthcare products Regulatory Agency (MHRA) authorised it on 5 August 2026. Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) listed ラプシド on 19 June 2026. The Australian Register of Therapeutic Goods (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. Symptomatic dermographism is now on the US label, based on a separate trial (RemIND, below). Other forms of urticaria are not on the US indication list.

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).

RemIND (NCT05976243 / CLOU064M12301) — a Phase 3 trial in chronic inducible urticaria, with separate groups for symptomatic dermographism, cold urticaria and cholinergic urticaria. Active but no longer taking new patients on ClinicalTrials.gov (record updated 15 Oct 2026; 362 enrolled across all groups). The US dermographism results come from its 115-person dermographism group (US label section 14.2). Canadian sites listed: Winnipeg, Hamilton, Trois-Rivières. Not an enrolment path.

NCT05513001 (CLOU064A2303B) — Phase 3b extension. Active but no longer taking new patients. Who it is for: 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 route.

NCT07816328: Phase 3, recruiting, chronic spontaneous urticaria only; 5 sites (3 in Japan, 1 in Hong Kong, 1 in South Korea).

Symptomatic dermographism is on the US label. The Canadian, EU and UK labels checked do not include it.

Commercial supply (labelled for adults with CSU whose symptoms continue despite H1 antihistamines, unless a local label says otherwise):

• United States
• Canada (authorised; listed as marketed since 6 Oct 2026 in Health Canada’s Drug Product Database)
• European Union (marketing authorisation from the European Commission)
• United Kingdom (authorised by the MHRA)
• Japan (listed by the PMDA)
• Australia (registered on the ARTG)
• Switzerland (authorised by Swissmedic)

China: the company reports approval; not yet confirmed on the regulator's website.

Approval matrix

Access by country

• United States: Allergist / dermatologist / immunologist. FDA-labelled 30 Sep 2025 for adults with CSU still symptomatic despite H1 antihistamines. Since 6 Oct 2026, it is also labelled for adults with symptomatic dermographism still symptomatic despite H1 antihistamines. Same dose for both. 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. Other forms of urticaria are not on the US indication list. Not shown to be safe and effective in children. Not a first-line antihistamine.
• Canada: Authorised (full NOC, 16 Jul 2026) and listed in Health Canada’s Drug Product Database as Marketed since 6 Oct 2026, DIN 02570076. Adult CSU still symptomatic despite H1 antihistamines. Symptomatic dermographism is not confirmed in Canada (not in the Product Monograph). Ask an allergy or 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 route 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. Symptomatic dermographism is not confirmed in the EU. 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, for CSU. Symptomatic dermographism is not confirmed in the UK. 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 conversation is for adults whose symptoms continue despite H1 antihistamines. It covers CSU where it is labelled, and symptomatic dermographism on the US label. That use is not confirmed in Canada, the EU or the UK. It is not a first-line antihistamine. It is not automatically for other inducible urticarias, vasculitis, or other itch diseases.

United States (prescribing information, revised October 2026):

• Adult.
• Chronic spontaneous urticaria, or symptomatic dermographism (added 6 Oct 2026; label section 1).
• Still has symptoms despite H1 antihistamine treatment.
• Other forms of urticaria are not on the indication list. The earlier "not indicated for other forms of urticaria" limitation was removed in the October 2026 label.
• 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.
• Inducible urticarias other than symptomatic dermographism on the US line (chronic inducible urticaria was an exclusion in REMIX; symptomatic dermographism was studied separately in RemIND).
• Symptomatic dermographism in Canada, the European Union or the United Kingdom (not confirmed on the labels checked 18 Oct 2026).
• Children (US and Canada: not established under 18; EU and UK: not established from 6 to 18, and should not be used 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)

Your doctor will follow the label of the country where it is prescribed.

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.

Symptomatic dermographism — RemIND (NCT05976243), US label section 14.2

The trial enrolled 115 adults who had symptomatic dermographism for at least 4 months and were still symptomatic on H1 antihistamines. They were randomly split into two equal groups: Rhapsido 25 mg twice daily or placebo for 24 weeks. Everyone could then take Rhapsido for 28 more weeks. Mean age 39.2; 71.3% women. The main measure was a complete response on a standard skin-provocation test (Total Fric Score 0 on the FricTest 4.0) at Week 12.

• Week 12: 29.3% on Rhapsido (17 of 58) vs 14.0% on placebo (8 of 57). The difference was 15.0 points, with a 95% confidence interval (the likely range) of 0.3 to 29.7. So the true gain could be small.
• Week 24: 32.8% vs 15.8%. Week 2: 29.3% vs 8.8%.
• Itch after the test (0–10 scale) fell by an average of 4.0 points vs 1.8 points at Week 2.

This is one 24-week placebo-controlled comparison in 115 people on background antihistamine. About 7 in 10 on Rhapsido did not reach complete response at Week 12.

How it is taken

Dose on US, Canadian, EU, and UK labels: 25 mg (one tablet) by mouth twice daily. The US dose for symptomatic dermographism is the same. 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.
• Symptomatic dermographism (RemIND; US label section 6.1): 58 people on Rhapsido vs 57 on placebo for 24 weeks. The label says safety, including bleeding, was consistent with the CSU trials.

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. “Is mine CSU, symptomatic dermographism, or another inducible urticaria? The US label lists only CSU and symptomatic dermographism.”
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 route. 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 close-up: 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 question is who pays (CDA-AMC SR0940 pending; provinces unknown). Health Canada’s Drug Product Database lists it as Marketed since 6 October 2026. 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. In the United States, it is also labelled (since 6 October 2026) for adults with symptomatic dermographism still symptomatic despite H1 antihistamines. That use is not confirmed in Canada, the EU or the UK. The Japanese, Australian and Swiss labels were not checked for this use. 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 route. 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 5 August 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
23. ClinicalTrials.gov RemIND NCT05976243 (symptomatic dermographism group) — https://clinicaltrials.gov/study/NCT05976243
24. Drugs@FDA NDA 218436 (SUPPL-1, Efficacy-New Indication, 6 October 2026) — https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=218436
25. US prescribing information, Revised 10/2026 (S-001; symptomatic dermographism added) — https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/218436s001lbl.pdf

Research team

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