Weekly Shot When Too Many Red Blood Cells Need Frequent Draws

Mimrylo (rusfertide; pronounced mim-rahy-loh) is a synthetic cyclic peptide that mimics hepcidin. It blocks the iron transporter ferroportin, which reduces iron available for new red blood cells and lowers hematocrit. It is not hydroxyurea, not interferon, not ruxolitinib, and not a cure. It is a once-weekly subcutaneous injection after reconstituting a lyophilized vial with the co-packaged diluent.

The FDA labelled it on 28 August 2026 for treatment of erythrocytosis in adults with polycythemia vera. The labelled starting dose is 19 mg once a week under the skin. The labelled weekly range is 9.5 mg to 108 mg, titrated to keep hematocrit below 45%.

Health Canada’s Notice of Compliance was not retrieved. That is unknown, not a no. Europe, Japan, and China authorisations were not retrieved either.

This is not a cure. Children are not established. It does not replace the need to manage clotting risk, cardiovascular risk, or other cytoreductive therapy your hematologist has already set.

Where this is taking place

Pivotal Week 32 readouts are done. VERIFY remains ACTIVE_NOT_RECRUITING on ClinicalTrials.gov because long-term follow-up runs toward mid-2027. That is not a new first-script enrolment slot. Access in the United States is a commercial prescription.

VERIFY (NCT05210790) — Phase 3, multicenter, randomized, double-blind, placebo-controlled, then open-label. Adults with PV who needed frequent phlebotomies despite standard care. Sponsor: Protagonist Therapeutics, Inc. Enrollment: 293. Status: ACTIVE_NOT_RECRUITING. hasExpandedAccess: false. Primary completion 21 Feb 2025. Estimated completion June 2027. Starting dose 19 mg SC weekly; titrated to maintain HCT <45%. Randomization 1:1 Mimrylo vs placebo Weeks 0–32; then open-label Mimrylo through Week 52 and long-term extension to Week 156.

Canadian sites on CT.gov (historical — not recruiting, not a DIN):

• University of Alberta — Edmonton, Alberta
• Sunnybrook Health Sciences Centre — Toronto, Ontario
• Princess Margaret Hospital — Toronto, Ontario
• Jewish General Hospital — Montreal, Quebec

These addresses are historical trial sites, not a walk-in clinic directory, and not a commercial Canadian product.

Other open rusfertide trials (not CA/US commercial doors):

• NCT07648030 — Phase 2 PV in Japan (Takeda). Status RECRUITING. Geography-limited; not a Canadian or US labelled path, and not PMDA approval.
• NCT07765602 — Phase 2 PV in China (Takeda). Status NOT_YET_RECRUITING. Not NMPA approval, and not a Canadian or US commercial door.

VERIFY (NCT05210790) remains the pivotal labelled study. For a US script, the label’s eligibility wording is ≥3 phlebotomies in the prior 28 weeks (or ≥5 in 1 year) — that is the USPI sentence, not CT.gov’s “6 months” text.

Commercial supply (labelled): United States. Canada: no retrieved NOC. EMA / UK / Australia / Japan / China: authorisation not retrieved.

Approval matrix

Access by country

• United States: Hematologist / myeloproliferative-neoplasm clinic. FDA-labelled 28 Aug 2026 for adults with PV erythrocytosis. Start 19 mg subcutaneously once weekly; adjust 9.5–108 mg to keep hematocrit below 45%. Doses above 54 mg need two injections the same week; doses above 82 mg split across day 1 and day 4 or 5. Reconstitute with the provided diluent; inject abdomen (≥2 inches from navel), front of thigh, or outer upper arm (upper arm only if a caregiver injects). Use within 4 hours of mixing. Store vials at room temperature 20–25 °C; protect from light; do not freeze. CBC every 2–4 weeks after start and during dose changes. Pregnancy test before start if of reproductive potential; effective contraception during treatment and for at least 30 days after the final dose; do not breastfeed during treatment and for 30 days after. Takeda US (USPI): 1-877-825-3327. Adverse events: same number or FDA MedWatch 1-800-FDA-1088. No copay dollars here. Prior authorization still applies. Children not established.

• Canada (zoom, not a different Access Level): No retrieved NOC. That is unknown, not a refusal — Canada is not dual Health Canada/FDA Approved on this piece. A specialist can ask Health Canada SAP for a non-marketed drug when conventional therapy has failed, is unsuitable, or is unavailable — manufacturer must agree to supply. SAP unknown. VERIFY Canadian sites above are historical; the trial is not recruiting and has no expanded access on CT.gov. Provincial / territorial / NIHB / RAMQ listing is N/A until there is a NOC. Do not mail-order a US carton. This zoom is not the Access Level.

• European Union / United Kingdom / Australia / Japan / China / Switzerland: Authorisation not retrieved. Specialist + local special-access / trial only if those programs apply. Do not DIY-import a US carton.

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

Who is eligible (from the USPI)

United States (USPI):

• Adults with polycythemia vera and erythrocytosis.
• VERIFY-style disease (how the study was built — use with your hematologist, not as a second indication sentence): needed ≥3 phlebotomies in the prior 28 weeks or ≥5 in the prior year because hematocrit was not controlled on ongoing standard care (phlebotomy alone, or phlebotomy plus hydroxyurea, interferon, ruxolitinib, or a combination).
• Dose: start 19 mg SC once weekly; titrate 9.5–108 mg to maintain HCT <45%.
• Pediatrics: not established.
• Contraindications: none on the USPI.

Not the labelled US indication:

• Children.
• A Canadian DIN (none retrieved).
• “Join VERIFY” as a way to start the drug — the trial is not recruiting.

What VERIFY showed (use the USPI)

These numbers are from USPI Table 5, not from a press release or the JCO LBA abstract alone.

VERIFY (NCT05210790) — Week 20 to Week 32 response (absence of phlebotomy eligibility):

• Mimrylo 76.9% (113/147) vs placebo 32.9% (48/146).
• Common risk difference 43.8% (95% CI 33.5%, 54.2%); p <0.0001.

Mean number of phlebotomies (baseline to Week 32):

• Mimrylo 0.53 vs placebo 1.82 (LSM difference −1.29; p <0.0001).

Maintaining HCT <45% (Week 0 to Week 32):

• Mimrylo 62.6% (92/147) vs placebo 14.4% (21/146).

PROMIS Fatigue Short Form 8a change at Week 32 (lower = less fatigue):

• Mimrylo −1.79 vs placebo +0.19 (LSM difference −1.98; p = 0.0252).

Phlebotomy eligibility on the label meant a confirmed HCT ≥45% that was ≥3 absolute points above baseline, or HCT ≥48%. Mean baseline HCT was about 42% in both arms. About 45% were on phlebotomy only at randomization; others were on phlebotomy plus hydroxyurea, interferon, ruxolitinib, or combinations. Roughly half were low-risk and half high-risk by age / prior thrombosis.

This is better hematocrit control and fewer blood draws over 32 weeks. It is not a proven reduction in strokes, heart attacks, or survival. Journals (JCO LBA3; Blood abstract) exist; a US clinic should still use the USPI tables.

How it is taken (US label)

• Start 19 mg subcutaneously once a week.
• Adjust between 9.5 mg and 108 mg weekly based on efficacy (keep HCT <45%) and safety (anemia, Grade ≥3 toxicity).
• Allow ≥2 weeks between dose increases.
• Doses >54 mg: two injections the same week.
• Doses >82 mg: first injection day 1; second on day 4 or 5.
• Reconstitute with the co-packaged diluent syringe; gently swirl (~2 minutes); do not shake; use within 4 hours.
• Inject abdomen (≥2 in from navel), front of thigh, or outer upper arm (caregiver only for upper arm). Rotate sites.
• Missed dose (once-weekly): if 1–4 days late, inject now and resume weekly; if >4 days late, inject now, next dose 3 days later, then resume. Two-times-weekly schedule has its own missed-dose rules — call the clinic if unsure.
• Store 20–25 °C in the original carton; do not freeze; protect from light.

Safety (USPI)

Contraindications: none.

New or worsening thrombocytosis. Platelets rose ~31% on average within 4 weeks; 36% exceeded 600 × 10⁹/L; 6% exceeded 1,000 × 10⁹/L. Monitor CBC every 2–4 weeks after start and during dose changes. Call for unusual bruising or bleeding, chest pain, shortness of breath, leg pain/swelling, or sudden severe headache.

Injection-site reactions. Highlights: 56% (Week 0–32). Body: 47% in VERIFY (erythema, itch, pain, swelling). Most Grade 1–2. Ice, topical steroid cream, antihistamine, or analgesic as needed. Two patients discontinued for ISR.

Anemia. 16% vs 4.1% placebo (Week 0–32). Dose reductions for anemia in ~10%.

Other ≥5% and ≥5 points above placebo: thrombocytosis 8%, dyspnea 8%.

Embryo-fetal toxicity. Animal data: malformations / embryo-fetal lethality at exposures below the maximum recommended human dose. Pregnancy test before start. Effective contraception during treatment and ≥30 days after final dose. Stop if pregnant. Do not breastfeed during treatment and for 30 days after (potential impaired iron absorption in the infant).

Immunogenicity. Anti-rusfertide antibodies in 34% (97/282) with median 61 weeks exposure; neutralizing in 36% of those; no clear effect on PK, efficacy, or safety identified in VERIFY.

Pediatrics: not established. Geriatrics: 25% were ≥65; no overall differences identified.

Research team (Who)

Names below are as they appear on primary sources.

• Takeda Pharmaceuticals America, Inc., Cambridge, MA — FDA applicant / USPI “Distributed by” / commercial. Medical information: 1-877-825-3327.
• Protagonist Therapeutics, Inc. — NCT05210790 lead sponsor.
• Andrew T. Kuykendall, MD, Moffitt Cancer Center — named as lead investigator in JCO 2025 LBA3 / company materials (attribution only; not a CT.gov site official for every centre).
• FDA press quotes Tanya Wroblewski, M.D. (Division of Nonmalignant Hematology) — regulator, not a treating clinic.

No Canadian site PI is named on CT.gov. The Canadian facility list is historical, not a clinic directory.

How to talk to a doctor

Bring the NCT number and the regulator that applies:

1. “I have polycythemia vera and I still need frequent phlebotomies. The FDA labelled rusfertide (Mimrylo) on 28 August 2026 as a once-weekly subcutaneous hepcidin mimetic starting at 19 mg, titrated to keep hematocrit below 45%. Is that a fit with my current hydroxyurea / interferon / ruxolitinib / phlebotomy plan?”
2. Platelets and CBC: “The label wants CBC every 2–4 weeks after start. Who orders that?”
3. Injection training: “Who teaches reconstitution and the two-injection / split-day schedule if my dose goes above 54 or 82 mg?”
4. Pregnancy / contraception / breastfeeding: “The label says contraception during treatment and 30 days after, and no breastfeeding for 30 days after the last dose.”
5. If Canada: “Is there a Health Canada NOC yet? If not, is SAP appropriate, or do we wait? VERIFY Canadian sites are not recruiting and CT.gov shows no expanded access.”
6. If outside the US: “Has my regulator authorised it, or are we looking at special access / travel with both specialists? Japan has an open Phase 2 (NCT07648030); China Phase 2 (NCT07765602) is not yet recruiting — neither is a Canadian commercial door.”
7. Fatigue and blood-draw burden: “VERIFY used PROMIS fatigue and phlebotomy counts — what does success look like for me at 8–12 weeks?”

Canada zoom: unknown / SAP unknown

Health Canada NOC was not retrieved. That is unknown, not a refusal — Canada is not dual Health Canada/FDA Approved (no NOC). SAP for a non-marketed drug is unknown. Provincial listings are unknown / not confirmed on this page (N/A until there is a NOC). US: labelled Rx. VERIFY Canadian sites are historical and not recruiting. No expanded access on CT.gov. Do not mail-order.

Bottom line

Mimrylo (rusfertide) is a once-weekly subcutaneous hepcidin mimetic labelled in the United States on 28 August 2026 for erythrocytosis in adults with polycythemia vera. Start at 19 mg; range 9.5–108 mg; titrate to keep hematocrit below 45%. In VERIFY, 76.9% vs 32.9% met the no-phlebotomy-eligibility response between Weeks 20 and 32 (USPI Table 5). Canada: NOC not retrieved — unknown, not refused. VERIFY Canadian sites are not an enrolment door. Authorized is not funded. Canada is a zoom.

Primary sources

1. FDA press announcement, 28 Aug 2026 — Mimrylo (rusfertide) approval — https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-its-kind-polycythemia-vera-rare-blood-disorder
2. ClinicalTrials.gov NCT05210790 VERIFY — https://clinicaltrials.gov/study/NCT05210790 3a. ClinicalTrials.gov NCT07648030 (Japan Phase 2 PV, RECRUITING) — https://clinicaltrials.gov/study/NCT07648030 3b. ClinicalTrials.gov NCT07765602 (China Phase 2 PV, NOT_YET_RECRUITING) — https://clinicaltrials.gov/study/NCT07765602
3. Kuykendall AT et al. J Clin Oncol. 2025;43(17_suppl.):LBA3 (journal LBA — not the USPI Table 5)
4. Blood 2025 abstract doi 10.1182/blood-2025-81 (cites JCO LBA3)