Introducing MIMRYLO™ (rusfertide): The first hepcidin mimetic to treat erythrocytosis in polycythemia vera (PV)^1,2

PV is characterized by erythrocytosis, causing iron dysregulation through hepcidin suppression^2-4

Iron dysregulation and erythrocytosis in PV

Diagram: hepcidin suppression in PV causes uncontrolled iron release, fueling erythrocytosis and elevated HCT — PV is characterized by erythrocytosis—the overproduction of RBCs in the bone marrow.^2-4

In people with PV, persistent erythrocytosis suppresses hepcidin, the body's regulator of iron homeostasis.²

**Step 1:** Hepcidin suppression causes uncontrolled iron release from iron stores²*

**Step 2:** Unrestricted iron availability to the bone marrow fuels further erythrocytosis^2-4

**Step 3:** As excess RBCs enter the bloodstream, HCT rises above the clinically established threshold of 45% for PV management^5,6

*Iron stores include: macrophages within the spleen and liver, hepatocytes (liver cells), and enterocytes (intestinal cells).²

MIMRYLO is the first hepcidin mimetic for PV, designed to deliver HCT control through targeted iron regulation^1,2

MIMRYLO mechanism of action

Diagram: MIMRYLO targets iron regulation, limiting bone marrow iron availability and normalizing RBC production — **Step 1:** MIMRYLO, a hepcidin mimetic, targets iron regulation and limits release of iron from iron stores^1,7*

**Step 2:** This limits iron availability to the bone marrow^1,4

**Step 3:** As a result, RBC production is normalized which is reflected in HCT counts^1,7

*Iron stores include: macrophages within the spleen and liver, hepatocytes (liver cells), and enterocytes (intestinal cells).²

HCT=hematocrit; RBC=red blood cell; PV=polycythemia vera.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

New or Worsening Thrombocytosis: MIMRYLO may increase platelet counts in patients with PV. Platelet counts generally plateaued on treatment by Week 8. After initiating MIMRYLO and during dose modifications, monitor CBC every 2 to 4 weeks or as clinically indicated. Platelet elevations associated with MIMRYLO may require cytoreductive therapy initiation, modification, or MIMRYLO dose modifications or discontinuation.

Injection-Site Reactions: Injection site reactions (including Grade 3 reactions) have been reported in patients treated with MIMRYLO. The most common injection site reactions reported were erythema, pruritus, pain, and swelling. Use ice, topical corticosteroid creams, antihistamines or analgesics, as needed, to treat injection site pain and swelling.

Embryo-Fetal Toxicity: Based on findings from animal reproduction studies, MIMRYLO may cause fetal harm when administered to a pregnant woman. Advise patients to stop taking MIMRYLO if they become pregnant.

ADVERSE REACTIONS

The most common (>15%) adverse reactions were injection site reactions (56%) and anemia (16%).

USE IN SPECIFIC POPULATIONS

Lactation: Because of the potential for serious adverse reactions in the breastfed child, including impaired iron absorption, advise patients not to breastfeed during treatment with MIMRYLO and for 30 days after the final treatment.

Females and Males of Reproductive Potential

Pregnancy Testing: Prior to initiating MIMRYLO, pregnancy testing is recommended for females of reproductive potential.
Contraception: Advise female patients of reproductive potential to use effective contraception during treatment with MIMRYLO and for at least 30 days after the final dose of MIMRYLO.

To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals at 1-844-662-8532 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see MIMRYLO (rusfertide) full Prescribing Information.

Introducing MIMRYLO™ (rusfertide): The first hepcidin mimetic to treat erythrocytosis in polycythemia vera (PV)^1,2

PV is characterized by erythrocytosis, causing iron dysregulation through hepcidin suppression^2-4

MIMRYLO is the first hepcidin mimetic for PV, designed to deliver HCT control through targeted iron regulation^1,2

IMPORTANT SAFETY INFORMATION AND INDICATION

WARNINGS AND PRECAUTIONS

ADVERSE REACTIONS

USE IN SPECIFIC POPULATIONS

INDICATION

PV is characterized by erythrocytosis, causing iron dysregulation through hepcidin suppression2-4

MIMRYLO is the first hepcidin mimetic for PV, designed to deliver HCT control through targeted iron regulation1,2

IMPORTANT SAFETY INFORMATION AND INDICATION

PV is characterized by erythrocytosis, causing iron dysregulation through hepcidin suppression^2-4

MIMRYLO is the first hepcidin mimetic for PV, designed to deliver HCT control through targeted iron regulation^1,2