BESREMi ROPEGINTERFERON ALFA-2B 500 ug/mL Injection, 1 syringe — NDC 73536-500-01 (Billing 73536-0500-01)
This is a package of 1 syringe of BESREMi ROPEGINTERFERON ALFA-2B 500 ug/mL Injection from PharmaEssentia USA, marketed since Nov 2021 and currently FDA-listed. It is this product's only package size.
NDC database record
One package, one record: these facts belong to NDC 73536-500-01 alone.
- Record
- FDA NDC Directory package listing · Human prescription drug
- Code segments
- 73536 labeler · 500 product · 01 package
- Package marketed since
- Nov 12, 2021
- Sample package
- No — commercial package
- Listing certified through
- Dec 31, 2027
- Barcode (UPC-A, from the NDC)
- 3 7353650001 7
- Medicaid fills, this package
- 618 prescriptions in the last four reported quarters
- FDA record last changed
- Sep 17, 2026
Identity & classification
Regulatory identifiers FDA, NLM and CMS codes for this package
Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification
- GSN (GCN sequence number): 082829
- GCN: 51515
- HICL (First Databank): 047669
- AHFS class code: 10:00.00.00
- RxCUI (RxNorm): 2587064
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 8, 2026
- FDA label on DailyMed · label index refreshed Oct 8, 2026
- RxNorm (NLM RxNav) · catalog refreshed Oct 1, 2026
- Medi-Span GPI (licensed)
- First Databank (licensed) · refreshed Oct 8, 2026
RxNorm drug class
This medicine belongs to the Interferon alfa-2b class.
Where does this data come from?
- RxClass (NLM) · catalog refreshed Oct 1, 2026
Clinical
Ropeginterferon alfa-2b injection is used to treat polycythemia vera (PV; a slow growing cancer of the blood in which the bone marrow makes too many red blood cells). Ropeginterferon alfa-2b injection is in a class of medications called interferons. It works by blocking the signals that cause cancer cells to multiply.
Read the full MedlinePlus article ↗- BESREMi is used in adults with essential thrombocythemia or polycythemia vera. These are bone marrow disorders that cause too many platelets or red blood cells.
- It is an injection under the skin, usually every 2 weeks. Your prescriber raises the dose gradually. You will need regular blood tests to guide the dose.
- Flu-like symptoms, tiredness, joint and muscle aches and itching are common. Liver enzyme changes and low blood counts can also show up on blood tests.
- Call right away if you feel depressed or have thoughts of self-harm. Also call for chest pain, signs of infection, unusual bleeding, trouble breathing, vision changes or severe sto...
Patient education
Supplement & herbal interactions
Where does this data come from?
- MedlinePlus (NLM) · refreshed Oct 8, 2026
- FDA label on DailyMed · label index refreshed Oct 8, 2026
Ask a licensed pharmacist directly — free, answered by our team.
Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | $8,942.49 | $8,942.49 / 1 syringe |
| Medicare drug plans payPart D · Q2 2026 | $9,867.44 | $9,867.44 / 1 syringe |
Where does this data come from?
- CMS NADAC weekly file
- CMS ASP pricing files · refreshed Sep 20, 2026
- CMS Medicaid State Drug Utilization Data · through Q4 2025
- CMS Part D plan pricing files · refreshed Sep 24, 2026
- VA National Acquisition Center price file
Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Marketing end | Status |
|---|---|---|---|---|
| 73536-0500-01 You're viewing this Main listing | 1 SYRINGE, GLASS in 1 CARTON / 1 mL in 1 SYRINGE, GLASS | 2021-11-12 | — | Active |
Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| BESREMi 500 ug/mLthis 73536-0500-01 | PharmaEssentia | 1 syringe | — | — | FDA listed | — |
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 8, 2026
- FDA Purple Book · refreshed Oct 5, 2026
- CMS NADAC weekly file
Availability & biosimilar status
Biologics have no small-molecule generics; biosimilar competition is tracked in the FDA Purple Book.
Why the date isn’t exact: Biosimilar timing can change because patents may be challenged, settled, licensed, added or removed, and litigation can move the real date earlier or later.
🛈 What do these terms mean?
- Biologic patent
- A patent the reference product’s maker has publicly listed. A biosimilar generally can’t launch until these expire — unless they’re invalidated or resolved in a settlement.
- Reference-product exclusivity
- A flat 12 years of FDA market protection from the biologic’s first licensure (the BPCIA). No biosimilar can be licensed before it ends, regardless of patents.
- Interchangeable exclusivity
- The first interchangeable biosimilar can earn a period as the only interchangeable version (pharmacists can substitute it without the prescriber).
- Earliest biosimilar (LOE)
- The latest of all the dates above — the soonest a biosimilar can realistically reach the market. Litigation and settlements can move it earlier.
Biologics have no small-molecule “generics” — competition comes from FDA-licensed biosimilars, tracked in the FDA Purple Book.
| Code | What it grants | Expires |
|---|---|---|
| RefProduct | Reference-product exclusivity (12-year, BPCIA) — no biosimilar can be licensed before this date | Nov 12, 2033 |
Is there a biosimilar for BESREMI 500 MCG/ML SYRINGE?
Why do different websites show different biosimilar dates?
Can a biosimilar launch before the last patent expires?
What does “current Purple Book estimate” mean?
What does “FDA listed” mean?
What does a patent or protection date mean here?
Where does this data come from?
- FDA Purple Book · refreshed Oct 5, 2026
Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
🧪 Avoiding an ingredient? See Ropeginterferon alfa-2b inactive ingredients by manufacturer: every current product's list side by side, so you can ask your pharmacy for the version that does not list it.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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0.05 mg / 1 mL
UNII Q40Q9N063P
Acetic acid is a weak organic acid commonly used in medicines as a buffer and pH adjuster. It helps maintain the proper acidity level to ensure the drug remains stable and effective in its formulation.
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10 mg / 1 mL
UNII LKG8494WBH
Benzyl alcohol is a clear liquid used as a preservative and solvent in medicines. It helps prevent bacterial and fungal growth and dissolves other ingredients to create uniform liquid formulations.
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0.05 mg / 1 mL
UNII 6OZP39ZG8H
Polysorbate 80 is a synthetic emulsifier derived from sorbitol and oleic acid. It helps mix oil and water-based ingredients together in medications and improves how the product disperses in the body.
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1.58 mg / 1 mL
UNII 4550K0SC9B
Sodium acetate is a salt derived from acetic acid. It acts as a buffer to help maintain the medicine's pH stability and may serve as a preservative or solubilizer in liquid formulations.
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8 mg / 1 mL
UNII 451W47IQ8X
Sodium chloride is common table salt. It's used in medicines as a buffer to maintain proper pH, as a filler to add bulk, or to adjust the osmotic balance in liquid formulations.
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UNII 059QF0KO0R
Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.
6 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.- FDA label on DailyMed · label index refreshed Oct 8, 2026
- FDA openFDA NDC Directory · synced Oct 8, 2026
Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
Why might an inactive ingredient be missing?
Can inactive ingredients matter?
Manufacturer & labeler
More NDCs from PharmaEssentia USA labeler code 73536
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 8, 2026
- Drugs@FDA
Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: RISK OF SERIOUS DISORDERS Risk of Serious Disorders: Interferon alfa products may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Patients should be monitored closely with periodic clinical and laboratory evaluations. Therapy should be withdrawn in patients with persistently severe or worsening signs or symptoms of these conditions.
In many, but not all cases, these disorders resolve after stopping therapy [see Warnings and Precautions ( 5.1 , 5,2 , 5.3 , 5.4 ) and Adverse Reactions ( 6.1 )] . WARNING: RISK OF SERIOUS DISORDERS See full prescribing information for complete boxed warning. Risk of Serious Disorders: Interferon alfa products may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders.
Monitor closely and withdraw therapy with persistently severe or worsening signs or symptoms of the above disorders. ( 5.1 , 5.2 , 5.3 , 5.4 )
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE BESREMi is an interferon alfa-2b indicated for: • The treatment of adults with essential thrombocythemia. ( 1.1 ) • The treatment of adults with polycythemia vera. ( 1.2 )
1.1Essential Thrombocythemia BESREMi is indicated for the treatment of adults with essential thrombocythemia.
1.2Polycythemia Vera BESREMi is indicated for the treatment of adults with polycythemia vera.
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Essential thrombocythemia: • The recommended dose of BESREMi is: a starting dose of 250 mcg by subcutaneous injection, at 2 weeks, increase the dose to 350 mcg by subcutaneous injection, at 4 weeks, increase to the maintenance dosage of 500 mcg by subcutaneous injection every 2 weeks. Maintain an every 2‑week schedule throughout treatment unless dose modification is required for safety or tolerability. Consider dose re-escalation in case of prior dose reduction, recovery, and lack of hematologic response.
( 2.2 , 2.3 , 5 ) Polycythemia vera: • The recommended dose of BESREMi is: a starting dosage of 100 mcg by subcutaneous injection every 2 weeks (50 mcg if receiving hydroxyurea). Increase the dose by 50 mcg every 2 weeks (up to a maximum of 500 mcg) until hematological parameters are stabilized ( 2.1 ). Interrupt or discontinue dosing if certain adverse reactions occur.
Dose re-increase to be considered in case of prior dose reduction, recovery, and lack of hematologic response. ( 2.2 , 2.3 , 5 )
2.1Pre-Treatment Testing Obtain a pregnancy test in females of reproductive potential prior to initiating treatment with BESREMi [see Use in Specific Populations ( 8.3 )] .
2.2Recommended Dosage Essential Thrombocythemia : • The recommended dose of BESREMi is: • A starting dose of 250 mcg by subcutaneous injection. • At 2 weeks, increase the dose to 350 mcg by subcutaneous injection. • At 4 weeks, increase to the maintenance dosage of 500 mcg by subcutaneous injection every 2 weeks. • Maintain an every 2-week schedule throughout treatment unless dose modification is required for safety or tolerability. • Consider dose re-escalation in case of prior dose reduction, recovery, and lack of hematologic response (platelets less than 400 × 10 9 /L and leukocytes less than 10 × 10 9 /L). • Monitor complete blood counts every 2 weeks during titration and every 3 to 6 months during maintenance.
Polycythemia Vera: Patients Not Already on Hydroxyurea • The recommended BESREMi starting dosage for patients not on hydroxyurea is 100 mcg by subcutaneous injection every two weeks. • Increase the dose by 50 mcg every two weeks (up to a maximum of 500 mcg), until the hematological parameters are stabilized (hematologic response: hematocrit less than 45%, platelets less than 400 × 10 9 /L, and leukocytes less than 10 × 10 9 /L). • Consider dose re-escalation in case of prior dose reduction, recovery, and lack of hematologic response.
Patients Transitioning from Hydroxyurea • When transitioning to BESREMi from hydroxyurea, start BESREMi at 50 mcg by subcutaneous injection every two weeks in combination with hydroxyurea. • Gradually taper off the hydroxyurea by reducing the total biweekly dose by 20-40% every two weeks during Weeks 3-12. • Increase the dose of BESREMi by 50 mcg every two weeks (up to a maximum of 500 mcg), until the hematological parameters are stabilized (hematocrit less than 45%, platelets less than 400 × 10 9 /L, and leukocytes less than 10 × 10 9 /L). • Discontinue hydroxyurea by Week 13.
Maintain the two-week dosing interval of BESREMi at which hematological stability is achieved for at least 1 year. After achievement of hematological stability for at least 1 year on a stable dose of BESREMi, the dosing interval may be expanded to every 4 weeks. Monitor patients closely especially during the titration phase.
Perform complete blood counts (CBC) regularly, every 2 weeks during the titration phase and every 3-6 months during the maintenance phase (after the patient’s optimal dose is established). Monitor CBC more frequently if clinically indicated. Phlebotomy as rescue treatment to normalize blood hyperviscosity may be necessary during the titration phase [see Clinical Pharmacology ( 12.2 )] .
2.3Dose Modifications Essential Thrombocythemia: If dose interruption occurs, resume dosing at previously attained levels. If drug-related toxicities arise, reduce the dose to the next lower level or interrupt in acc… [Excerpted — this section continues on DailyMed.]
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS BESREMi is a clear and colorless to slightly yellowish solution available as: • Prefilled Syringe Injection: 500 mcg/mL in a single-dose prefilled syringe • Prefilled Pen Injector Injection: 500 mcg/0.5 mL in a single-dose prefilled pen injector • Injection: 500 mcg/mL solution in a single-dose prefilled syringe ( 3 ) • Injection: 500 mcg/0.5 mL solution in a single-dose prefilled pen injector ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS BESREMi is contraindicated in patients with: • Existence of, or history of severe psychiatric disorders, particularly severe depression, suicidal ideation, or suicide attempt. • Hypersensitivity to interferons including interferon alfa-2b or any of the inactive ingredients of BESREMi. • Moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment. • History or presence of active serious or untreated autoimmune disease. • Immunosuppressed transplant recipients. BESREMi is contraindicated in patients with: • Existence of, or history of severe psychiatric disorders, particularly severe depression, suicidal ideation or suicide attempt ( 4 ) • Hypersensitivity to interferons or to any of the inactive ingredients in BESREMi ( 4 ) • Hepatic impairment (Child-Pugh B or C) ( 4 ) • History or presence of active serious or untreated autoimmune disease ( 4 ) • Immunosuppressed transplant recipients ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS • Depression and Suicide: Monitor for symptoms and need for treatment. ( 5.1 ) • Endocrine Toxicity: Discontinue if endocrine disorders occur that cannot be medically managed. ( 5.2 ) • Cardiovascular Toxicity: Avoid use in patients with severe or unstable cardiovascular disease.
Monitor patients with history of cardiovascular disorders more frequently. ( 5.3 ) • Hematologic and Hemorrhagic Disorders: Perform blood counts at baseline, every 2 weeks during titration, and at least every 3-6 months during maintenance treatment. ( 5.4 ) • Hypersensitivity Reactions: Stop treatment and immediately manage reaction.
( 5.5 ) • Pancreatitis: Consider discontinuation if confirmed pancreatitis. ( 5.6 ) • Colitis: Discontinue if signs or symptoms of colitis. ( 5.7 ) • Pulmonary Toxicity: Discontinue if pulmonary infiltrates or pulmonary function impairment.
( 5.8 ) • Ophthalmologic Toxicity: Monitor for ocular toxicity. Promptly evaluate eye symptoms and discontinue if new or worsening eye disorders. ( 5.9 ) • Hyperlipidemia: Monitor serum triglycerides before BESREMi treatment and intermittently during therapy and manage when elevated.
( 5.10 ) • Hepatotoxicity: Monitor liver enzymes and hepatic function at baseline and during treatment. Reduce dose or discontinue depending on severity. ( 5.11 ) • Renal Toxicity: Monitor serum creatinine at baseline and during therapy.
Discontinue if severe renal impairment develops. ( 5.12 ) • Dental and Periodontal Toxicity: Advise on good oral hygiene and regular dental examinations. ( 5.13 ) • Dermatologic Toxicity: Consider discontinuing if clinically significant dermatologic toxicity.
( 5.14 ) • Driving and Operating Machinery: Advise patients to avoid driving or using machinery if they experience dizziness, somnolence, or hallucination. ( 5.15 ) • Embryo-Fetal Toxicity: Can cause fetal harm. ( 5.16 )
5.1Depression and Suicide Life-threatening or fatal neuropsychiatric reactions have occurred in patients receiving interferon alfa products, including BESREMi. These reactions may occur in patients with and without previous psychiatric illness. Psychiatric reactions have been observed in 10% of BESREMi-treated patients with essential thrombocythemia including depression, adjustment disorder with depressed mood, and depressed mood.
Serious neuropsychiatric reactions have been observed in 3% of BESREMi-treated patients with polycythemia vera, including depression, depressive symptoms, depressed mood, and listlessness. Of these cases, 3.4% of the patients recovered with temporary drug interruption and 2.8% stopped BESREMi treatment. Other central nervous system effects, including suicidal ideation, attempted suicide, aggression, bipolar disorder, mania and confusion have been observed with other interferon alfa products.
BESREMi is contraindicated in patients with a history of severe psychiatric disorders, particularly severe depression, suicidal ideation, or suicide attempt [see Contraindications ( 4 )] . Closely monitor patients for any symptoms of psychiatric disorders and consider psychiatric consultation and treatment if such symptoms emerge. If psychiatric symptoms worsen, it is recommended to discontinue BESREMi therapy.
5.2Endocrine Toxicity Endocrine toxicity has occurred in patients receiving interferon alfa products, including BESREMi. These toxicities may include worsening hypothyroidism and hyperthyroidism. Autoimmune thyroiditis and hyperglycemia, including new onset type 1 diabetes, have been reported in patients receiving interferon alfa-2b products.
Endocrine toxicities included hyperthyroidism (1.1%), hypothyroidism (1.1%), autoimmune thyroiditis (0.5%), and thyroiditis (0.5%) in BESREMi-treated patients with essential thrombocythemia. Endocrine toxicities included hyperthyroidism (4.5%), hypothyroidism (3.9%), and autoimmune thyroiditis/thyroiditis (2.8%) in BESREMi-treated patients with polycythemia vera. Do not use BESREMi in patients with active serious… [Excerpted — this section continues on DailyMed.]
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling. • Depression and Suicide [see Warnings and Precautions ( 5.1 )] • Endocrine Toxicity [see Warnings and Precautions ( 5.2 )] • Cardiovascular Toxicity [see Warnings and Precautions ( 5.3 )] • Hematologic and Hemorrhagic Disorders [see Warnings and Precautions ( 5.4 )] • Hypersensitivity Reactions [see Warnings and Precautions ( 5.5 )] • Pancreatitis [see Warnings and Precautions ( 5.6 )] • Colitis [see Warnings and Precautions ( 5.7 )] • Pulmonary Toxicity [see Warnings and Precautions ( 5.8 )] • Ophthalmologic Toxicity [see Warnings and Precautions ( 5.9 )] • Hyperlipidemia [see Warnings and Precautions ( 5.10 )] • Hepatotoxicity [see Warnings and Precautions ( 5.11 )] • Renal Toxicity [see Warnings and Precautions ( 5.12 )] • Dental and Periodontal Toxicity [see Warnings and Precautions ( 5.13 )] • Dermatologic Toxicity [see Warnings and Precautions ( 5.14 )] • Driving and Operating Machinery [see Warnings and Precautions ( 5.15 )] • Embryo-Fetal Toxicity [see Warnings and Precautions ( 5.16 )] • Essential thrombocythemia: The most common adverse reactions reported in >20% of patients were transaminase elevations, anemia, pyrexia, beta 2 microglobulin urine increased, bacterial infection, pruritus, and weight decreased.
( 6 ) • Polycythemia vera: The most common adverse reactions reported in >40% of patients were influenza-like illness, arthralgia, fatigue, pruritus, nasopharyngitis, and musculoskeletal pain. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact PharmaEssentia at 1-800-999-2449 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Essential Thrombocythemia The pooled safety population described in the Warnings and Precautions section reflects exposure to BESREMi as monotherapy for the treatment of essential thrombocythemia dosed every 2 weeks in 182 patients in an open-label trial [P1101 ET, SURPASS ET] and a single-arm trial [A22-301, EXCEED ET].
The mean age was 56 years (range: 21 to 84 years). There were 104 (57%) women, 78 (43%) men, and 93 (51%) Asian, 76 (42%) Caucasian, 5 (2.7%) Black or African American, 5 (2.7%) Other, and 3 (1.6%) Hispanic patients were included in the studies. Among 182 patients who received BESREMi, 70 (39%) patients were exposed for >56 weeks (>14 months).
The mean (SD) dose of BESREMi was 394.9 (98.4) mcg during the treatment period. In this pooled safety population, the most common adverse reactions in ≥10% of BESREMi-treated patients were aspartate aminotransferase increased (44%), alanine aminotransferase increased (43%), fatigue (31%), anemia (24%), white blood cell count decreased (23%), neutrophil count decreased (22%), pruritus (17%), gamma-glutamyltransferase increased (16%), alopecia (16%), headache (15%), diarrhea (13%), nausea (13%), beta 2 microglobulin urine increased (12%), influenza like illness (11%), and myalgia (11%).
The safety findings described below reflect exposure to BESREMi as monotherapy for the treatment of essential thrombocythemia in 91 patients in the SURPASS ET study [see Clinical Studies ( 14 )] . Among the 91 patients receiving BESREMi, 55% were exposed for 9 to 13 months and 36% were exposed for more than 13 months. Serious adverse reactions were reported in 2.2% of patients treated with BESREMi in the SURPASS ET study and included vascular headache and drug eruption.
Adverse reactions requiring permanent discontinuation of patients treated with BESREMi occurred in 1.1% patient each and included aspartate aminotransferase increased, alanine aminotransferase increased, gamma-glutamyltransferase increased, pneumonitis, pulmonary hypertension, thyr… [Excerpted — this section continues on DailyMed.]
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS • Monitor patients taking CYP450 substrates with a narrow therapeutic index for adverse reactions to inform the need for dose adjustment of the concomitant drug ( 7.1 ) • Avoid use with myelosuppressive agents and monitor patients receiving the combination for effects of excessive myelosuppression ( 7.2 ) • Avoid use with narcotics, hypnotics or sedatives. Monitor patients receiving the combination for excessive central nervous system toxicity ( 7.3 )
7.1Drugs Metabolized by Cytochrome P450 Certain proinflammatory cytokines, including interferons, can suppress CYP450 enzymes resulting in increased exposures of some CYP substrates [see Clinical Pharmacology ( 12.3 )] . Therefore, patients on BESREMi who are receiving concomitant drugs that are CYP450 substrates with a narrow therapeutic index should be monitored to inform the need for dosage modification for these concomitant drugs.
7.2Myelosuppressive Agents Concomitant use of BESREMi and myelosuppressive agents can produce additive myelosuppression. Avoid use and monitor patients receiving the combination for effects of excessive myelosuppression [see Warnings and Precautions ( 5.4 )] .
7.3Narcotics, Hypnotics or Sedatives Concomitant use of BESREMi and narcotics, hypnotics or sedatives can produce additive neuropsychiatric side effects. Avoid use and monitor patients receiving the combination for effects of excessive CNS toxicity [see Warnings and Precautions ( 5.1 )] .
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS • Pregnancy: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception. ( 8.1 , 8.3 ) • Lactation: Breastfeeding not recommended. ( 8.2 ) • Renal Impairment: Avoid use in patients with eGFR <30 mL/min. ( 8.6 )
8.1Pregnancy Risk Summary Available human data with BESREMi use in pregnant women are insufficient to identify a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. An abortifacient effect was reported in cynomolgus monkeys receiving ropeginterferon alfa-2b ( see Data ). Based on mechanism of action and the role of interferon alfa in pregnancy and fetal development, BESREMi can cause fetal harm and should be assumed to have abortifacient potential when administered to a pregnant woman.
There are adverse effects on maternal and fetal outcomes associated with polycythemia vera in pregnancy (see Clinical Considerations ) . Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage is 2-4% and 15-20%, respectively. Data Animal Data In an embryo-fetal development study, pregnant cynomolgus monkeys received subcutaneous injection of ropeginterferon alfa-2b twice weekly during the period of organogenesis (Gestation Days 20-48).
Maternal toxicity, characterized by a significant decline in food consumption and transient body weight loss, occurred at all dose levels and ropeginterferon alfa-2b was abortifacient and caused embryonic death at exposures 275-times (C max ) and 64-times (AUC) the human exposure at the maximum recommended human dose of 500 mcg. There were no effects on fetal developmental parameters or abnormalities in the surviving fetuses (GD 100) where the ropeginterferon alfa-2b exposures achieved in pregnant cynomolgus monkeys during the first trimester were 961-times (C max ) and 224-times (AUC) the human exposure at the maximum recommended human dose of 500 mcg.
Clinical Considerations Disease-Associated Maternal and/or Embryo-Fetal Risk Untreated polycythemia vera during pregnancy is associated with adverse maternal outcomes such as thrombosis and hemorrhage. Adverse pregnancy outcomes associated with polycythemia vera include increased risk for miscarriage.
8.2Lactation There are no data on the presence of BESREMi in human or animal milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in breastfed children from BESREMi, advise women not to breastfeed during treatment and for 8 weeks after the final dose.
8.3Females and Males of Reproductive Potential BESREMi can cause embryo-fetal harm when administered to a pregnant woman [see Use in Specific Populations ( 8.1 )] . Pregnancy Testing Pregnancy testing prior to BESREMi treatment is recommended for females of reproductive potential. Contraception Females Advise female patients of reproductive potential to use effective contraception during treatment with BESREMi and for at least 8 weeks after the final dose.
Infertility Females Based on its mechanism of action, BESREMi can cause disruption of the menstrual cycle [see Clinical Pharmacology ( 12.1 )] . No animal fertility studies have been conducted with BESREMi.
8.4Pediatric Use Safety and effectiveness in pediatric patients have not been established.
8.5Geriatric Use Of the total number of BESREMi-treated patients in the essential thrombocythemia studies, 65 (36%) were 65 years of age and older, while 15 (8%) were 75 years of age and older [see Clinical Studies ( 14 )] . Of the total number of BESREMi-treated patients in the polycythemia studies, 17 (33%) were 65 years of age and older, while 5… [Excerpted — this section continues on DailyMed.]
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Available human data with BESREMi use in pregnant women are insufficient to identify a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. An abortifacient effect was reported in cynomolgus monkeys receiving ropeginterferon alfa-2b ( see Data ). Based on mechanism of action and the role of interferon alfa in pregnancy and fetal development, BESREMi can cause fetal harm and should be assumed to have abortifacient potential when administered to a pregnant woman.
There are adverse effects on maternal and fetal outcomes associated with polycythemia vera in pregnancy (see Clinical Considerations ) . Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage is 2-4% and 15-20%, respectively. Data Animal Data In an embryo-fetal development study, pregnant cynomolgus monkeys received subcutaneous injection of ropeginterferon alfa-2b twice weekly during the period of organogenesis (Gestation Days 20-48).
Maternal toxicity, characterized by a significant decline in food consumption and transient body weight loss, occurred at all dose levels and ropeginterferon alfa-2b was abortifacient and caused embryonic death at exposures 275-times (C max ) and 64-times (AUC) the human exposure at the maximum recommended human dose of 500 mcg. There were no effects on fetal developmental parameters or abnormalities in the surviving fetuses (GD 100) where the ropeginterferon alfa-2b exposures achieved in pregnant cynomolgus monkeys during the first trimester were 961-times (C max ) and 224-times (AUC) the human exposure at the maximum recommended human dose of 500 mcg.
Clinical Considerations Disease-Associated Maternal and/or Embryo-Fetal Risk Untreated polycythemia vera during pregnancy is associated with adverse maternal outcomes such as thrombosis and hemorrhage. Adverse pregnancy outcomes associated with polycythemia vera include increased risk for miscarriage.
🧒 Pediatric Use ▾
8.4Pediatric Use Safety and effectiveness in pediatric patients have not been established.
🧓 Geriatric Use ▾
8.5Geriatric Use Of the total number of BESREMi-treated patients in the essential thrombocythemia studies, 65 (36%) were 65 years of age and older, while 15 (8%) were 75 years of age and older [see Clinical Studies ( 14 )] . Of the total number of BESREMi-treated patients in the polycythemia studies, 17 (33%) were 65 years of age and older, while 5 (10%) were 75 years of age and older. Clinical studies of BESREMi did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects.
Other reported clinical experience has not identified differences in responses between the elderly and younger patients.
🆘 Overdosage ▾
10 OVERDOSAGE Overdosage of BESREMi may result in influenza-like symptoms or other adverse reactions. There is no antidote to BESREMi overdosage. In case of an overdose, frequently monitor signs and symptoms for adverse reactions. Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Interferon alfa belongs to the class of type I interferons, which exhibit their cellular effects in polycythemia vera and essential thrombocythemia in the bone marrow by binding to a transmembrane receptor termed interferon alfa receptor (IFNAR). Binding to IFNAR initiates a downstream signaling cascade through the activation of kinases, in particular Janus kinase 1 (JAK1) and tyrosine kinase 2 (TYK2) and activator of transcription (STAT) proteins. Nuclear translocation of STAT proteins controls distinct gene-expression programs and exhibits various cellular effects.
The actions involved in the therapeutic effects of interferon alfa in polycythemia vera and essential thrombocythemia are not fully elucidated.
12.2Pharmacodynamics The efficacy of ropeginterferon alfa-2b-njft is dependent on the stabilization of hematological parameters (hematocrit <45%, platelets <400 × 10 9 /L and leukocytes <10 × 10 9 /L). Pharmacokinetic-pharmacodynamic analyses have demonstrated that the reduction in the individual hematological parameters is dependent on ropeginterferon alfa-2b-njft concentrations. Complete hematological response (CHR, defined as a patient achieving hematocrit <45% without phlebotomy [at least 2 months since last phlebotomy], platelets ≤400 × 10 9 /L and leukocytes ≤10 × 10 9 /L) increased with increasing ropeginterferon alfa-2b-njft concentration over time.
Based on the exposure-response (E-R) analyses using data from the PEGINVERA study in patients with polycythemia vera, the predicted probability of CHR (95% Prediction Intervals) was 22% (11% – 34%) before treatment, 50% (38% – 62%) at week 20 (end of titration), 64% (47% – 78%) at week 52, and 70% (55% – 88%) at week 104. The E-R analyses show that the maximum probability of CHR is reached after 2 years of continuous treatment.
12.3Pharmacokinetics In patients with essential thrombocythemia, following subcutaneous administration of BESREMi, peak serum concentrations (Cmax) were reached between 62 to 123 hours post-dose (T max ). Exposure appeared generally dose‑proportional following repeated subcutaneous doses of 250 to 500 mcg at Week 12. In patients with polycythemia vera, the estimated steady state C max , C min and area under the curve (AUC) after a two-week dosing interval of BESREMi over a dose range of 100 mcg to 500 mcg ranged from 4.4 – 31 ng/mL, 1.4 – 12 ng/mL, and 1,011 – 7,809 ng × h/mL, respectively.
The estimated steady state C max occurs between 2 to 5 days. Absorption The estimated geometric mean (CV%) of the absorption rate constant of BESREMi is 0.12 day -1 (27%) in patients with polycythemia vera. Distribution The estimated geometric mean (CV%) of apparent volume of distribution of BESREMi is
4.8L (21%) in patients with polycythemia vera. Elimination BESREMi undergoes receptor independent degradation/excretion and receptor binding and subsequent degradation of the drug-receptor complex. The half-life of BESREMi is approximately 7 days and the clearance is approximately 1.7-2.5 L/h in patients with polycythemia vera over a dose range of 100 mcg to 500 mcg, respectively.
In patients with essential thrombocythemia, the median terminal phase half-life (t 1/2,λz ) is 122 hours following a single subcutaneous dose. Following repeated subcutaneous dosing, the median t 1/2,λz ranged from 210 to 251 hours across doses of 250 mcg to 500 mcg at Week 12. Specific Populations No clinically significant differences in the pharmacokinetics of BESREMi were observed based on age, sex, body surface area, and JAK2V617F mutation.
Drug Interactions Clinical Studies No clinical studies evaluating the drug interaction potential of BESREMi have been conducted. In Vitro Studies In vitro studies indicate that BESREMi exhibited time-dependent inhibitory potential on CYP2A6. BESREMi did not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 in human liver microsomes.
BESREMi is not expected to induce C… [Excerpted — this section continues on DailyMed.]
🧬 Mechanism of Action ▾
12.1Mechanism of Action Interferon alfa belongs to the class of type I interferons, which exhibit their cellular effects in polycythemia vera and essential thrombocythemia in the bone marrow by binding to a transmembrane receptor termed interferon alfa receptor (IFNAR). Binding to IFNAR initiates a downstream signaling cascade through the activation of kinases, in particular Janus kinase 1 (JAK1) and tyrosine kinase 2 (TYK2) and activator of transcription (STAT) proteins. Nuclear translocation of STAT proteins controls distinct gene-expression programs and exhibits various cellular effects.
The actions involved in the therapeutic effects of interferon alfa in polycythemia vera and essential thrombocythemia are not fully elucidated.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied • Prefilled syringe – 500 mcg/mL BESREMi (ropeginterferon alfa-2b-njft) injection is a sterile, clear and colorless to slightly yellowish solution for subcutaneous administration in a single-dose prefilled syringe. Each carton contains one 500 mcg/mL prefilled syringe with a 30 gauge, ½ inch safety hypodermic needle (NDC 73536-500-01). • BESREMi Pen – 500 mcg/0.5 mL BESREMi Pen (ropeginterferon alfa-2b-njft) injection is a sterile, clear and colorless to slightly yellowish solution for subcutaneous administration in a single-dose prefilled pen injector.
Each carton contains one 500 mcg/0.5 mL prefilled pen injector with a 30 gauge, 8 mm needle (NDC 73536-511-01). Storage and Handling Store in the refrigerator between 36°F to 46°F (2°C to 8°C) in the original carton to protect from light. DO NOT FREEZE.
📋 Description ▾
11 DESCRIPTION Ropeginterferon alfa-2b-njft, an interferon alfa-2b, is an N-terminal monopegylated covalent conjugate of proline interferon alfa-2b, produced in Escherichia coli cells by recombinant DNA technology, with a methoxy polyethylene glycol (mPEG) moiety. Ropeginterferon alfa-2b-njft has an approximate molecular weight of 60 kDa and the approximate molecular weight of the PEG portion of the molecule is 40 kDa. BESREMi (ropeginterferon alfa-2b-njft) injection is a sterile, clear and colorless to slightly yellowish solution for subcutaneous use supplied in a single-dose prefilled syringe or in a single-dose prefilled pen injector.
Each prefilled syringe delivers 1 mL of solution containing 500 mcg of ropeginterferon alfa-2b-njft and benzyl alcohol (10 mg), glacial acetic acid (0.05 mg), polysorbate 80 (0.05 mg), sodium acetate (1.58 mg), sodium chloride (8 mg), and Water for Injection, USP. The pH is approximately 6. Each prefilled pen injector delivers 0.5 mL of solution containing 500 mcg of ropeginterferon alfa-2b-njft and benzyl alcohol (5 mg), glacial acetic acid (0.025 mg), polysorbate 80 (0.025 mg), sodium acetate (0.79 mg), sodium chloride (4 mg), and Water for Injection, USP.
The pH is approximately 6.
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use). Depression and Suicide Inform patients, their caregivers, and family members that suicidal ideation and behavior, as well as new onset or worsening depression have been reported in patients treated with BESREMi. Advise them to be aware of any unusual changes in mood or behavior, new onset or worsening of depression, or the emergence of suicidal thoughts or behavior.
Instruct patients, caregivers, and family members to report signs or symptoms of depression to their healthcare provider right away, but to discontinue BESREMi immediately and seek immediate medical attention if suicidal ideation or attempts occur [see Warnings and Precautions ( 5.1 )] . Endocrine Toxicity Advise patients to report any signs or symptoms of diabetes or thyroid dysfunction [ see Warnings and Precautions ( 5.2 ) ]. Cardiovascular Toxicity Advise patients to report signs or symptoms of cardiovascular toxicity to their healthcare provider [see Warnings and Precautions ( 5.3 )].
Hematologic and Hemorrhagic Disorders Advise patients to seek prompt medical attention if they experience weakness/fatigue, fever, easy bruising, or frequent nose bleeds [see Warnings and Precautions ( 5.4 )]. Hypersensitivity Reactions Advise patients to seek immediate medical attention if they experience any symptoms of serious hypersensitivity reactions [see Warnings and Precautions ( 5.5 )]. Pancreatitis Advise patients to report signs or symptoms of pancreatitis [see Warnings and Precautions ( 5.6 )] .
Colitis Advise patients to report signs or symptoms of colitis [see Warnings and Precautions ( 5.7 )] . Pulmonary Toxicity Advise patients to report signs or symptoms of pulmonary toxicity [see Warnings and Precautions ( 5.8 )] . Ophthalmologic Toxicity Advise patients to report visual changes and to have eye examinations before and during treatment [see Warnings and Precautions ( 5.9 )] .
Hyperlipidemia Advise patients that BESREMi may increase blood triglycerides and that they will need blood testing to monitor for this toxicity [see Warnings and Precautions ( 5.10 )] . Hepatotoxicity Advise patients to report signs or symptoms of hepatic toxicity to their healthcare provider [see Warnings and Precautions ( 5.11 ) and Use in Specific Populations ( 8.7 )] . Renal Toxicity Advise patients to report signs or symptoms of kidney disease [see Warnings and Precautions ( 5.12 ) and Use in Specific Populations ( 8.6 )] .
Dental and Periodontal Toxicity Advise patients to maintain good oral hygiene and to have regular dental examinations [see Warnings and Precautions ( 5.13 )] . Dermatologic Toxicity Advise patients to seek medical attention if significant pruritus, alopecia, rash and/or other dermatological toxicities occur [see Warnings and Precautions ( 5.14 )] . Hazardous Occupations/Operating Machinery Advise patients to refrain from engaging in operating heavy or potentially dangerous machinery until they know how BESREMi will affect their abilities.
Advise patients who experience dizziness, somnolence, and hallucinations not to drive or use heavy machinery [see Warnings and Precautions ( 5.15 )] . Pregnancy and Contraception Advise women about the need to use an effective method of contraception while taking BESREMi and for at least 8 weeks after the final dose [see Use in Specific Populations ( 8.1 , 8.3 )] . Lactation Advise women not to breastfeed during treatment and for 8 weeks after the final dose [see Use in Specific Populations ( 8.2 )] .
Instruction on Injection Technique Instruct patients on proper storage, preparation and administration techniques for BESREMi. Instruct patients who are self-administering to inject the prescribed dose of BESREMi [see Dosage and Administration ( 2.4 )] . Manufactured by: PharmaEssentia Corporation 13F, No.
3, Park Street Nangang District, Taipei 115, Taiwan U.S. License number 2155 Distributed by:… [Excerpted — this section continues on DailyMed.]
💬 Medication Guide ▾
Medication Guide BESREMi ® (bez-reh-me) ropeginterferon alfa-2b-njft injection, for subcutaneous use What is the most important information I should know about BESREMi? BESREMi can cause serious side effects that may cause death, be life threatening, or worsen certain serious conditions that you may already have. Tell your healthcare provider right away if you get any of the problems listed below during treatment with BESREMi. • Mental health problems, including depression and suicide.
BESREMi may cause you to develop mood or behavior problems that may get worse during treatment with BESREMi or after your last dose. Your healthcare provider should closely monitor you for new or worsening depression and any unusual changes in mood or behavior during treatment with BESREMi. If you have thoughts of hurting yourself or thoughts of suicide, stop using BESREMi right away.
You, your caregiver, or family member should tell your healthcare provider or get medical help right away if you develop any of the following signs or symptoms, especially if they are new, worse, or worry you: o thoughts about suicide or dying o new or worse depression o feeling very agitated or restless o trouble sleeping (insomnia) o acting aggressive, being angry, or violent o an extreme increase in activity or talking (mania) o suicide attempts o new or worse anxiety o panic attacks o new or worse irritability o acting on dangerous impulses o other unusual changes in behavior or mood • New or worsening autoimmune problems.
BESREMi may cause autoimmune problems (a condition where the body’s immune cells attack other cells or organs in the body), including thyroid problems, increased blood sugar (hyperglycemia), and type I diabetes. In some people who already have an autoimmune problem, it may get worse during your treatment with BESREMi. Tell your healthcare provider if you get any of the following symptoms: o tiredness o urinating more often than normal o very thirsty o increase in appetite o problems concentrating o sensitivity to heat or cold temperature o weight changes o skin changes • Heart and blood vessel (cardiovascular) problems.
BESREMi may cause heart problems, including problems with your heart muscle (cardiomyopathy), heart attack, abnormal heart rhythm (atrial fibrillation), and decreased or sudden loss of blood flow to your heart. BESREMi may also cause blood clots (thrombotic events) in your brain, lungs, arms, and legs. Your healthcare provider should closely monitor you during treatment with BESREMi if you have a history of heart problems or blood clots.
You should not use BESREMi if you have: o high blood pressure that is not controlled o congestive heart failure o a serious abnormal heart rhythm o narrowing of the arteries to your heart o certain types of chest pain (angina) o a recent stroke or heart attack Tell your healthcare provider right away if you develop any of the following signs and symptoms during treatment with BESREMi: o fast heart rate or abnormal heart beat o trouble breathing or chest pain o pain, swelling, or redness in the arms, legs, ankles, or feet o tiredness o sudden confusion o numbness or weakness o loss of coordination o trouble speaking clearly o sudden vision changes If symptoms get worse, or become severe and do not go away, your healthcare provider may tell you to stop using BESREMi permanently.
For some people, these symptoms may go away after they stop using BESREMi. See “What are the possible side effects of BESREMi?” for more information about side effects. What is BESREMi?
BESREMi is a prescription medicine that is used to treat adults with: • essential thrombocythemia. • polycythemia vera. It is not known if BESREMi is safe and effective in children. Who should not use BESREMi?
Do not use BESREMi if you: • have or had severe mental health problems, especially severe depression, thoughts of suicide, or attempted suicide • are allergic to another interferon product, including interferon alfa-2b, or to any of… [Excerpted — this section continues on DailyMed.]
🧬 Pharmacokinetics ▾
12.3Pharmacokinetics In patients with essential thrombocythemia, following subcutaneous administration of BESREMi, peak serum concentrations (Cmax) were reached between 62 to 123 hours post-dose (T max ). Exposure appeared generally dose‑proportional following repeated subcutaneous doses of 250 to 500 mcg at Week 12. In patients with polycythemia vera, the estimated steady state C max , C min and area under the curve (AUC) after a two-week dosing interval of BESREMi over a dose range of 100 mcg to 500 mcg ranged from 4.4 – 31 ng/mL, 1.4 – 12 ng/mL, and 1,011 – 7,809 ng × h/mL, respectively.
The estimated steady state C max occurs between 2 to 5 days. Absorption The estimated geometric mean (CV%) of the absorption rate constant of BESREMi is 0.12 day -1 (27%) in patients with polycythemia vera. Distribution The estimated geometric mean (CV%) of apparent volume of distribution of BESREMi is
4.8L (21%) in patients with polycythemia vera. Elimination BESREMi undergoes receptor independent degradation/excretion and receptor binding and subsequent degradation of the drug-receptor complex. The half-life of BESREMi is approximately 7 days and the clearance is approximately 1.7-2.5 L/h in patients with polycythemia vera over a dose range of 100 mcg to 500 mcg, respectively.
In patients with essential thrombocythemia, the median terminal phase half-life (t 1/2,λz ) is 122 hours following a single subcutaneous dose. Following repeated subcutaneous dosing, the median t 1/2,λz ranged from 210 to 251 hours across doses of 250 mcg to 500 mcg at Week 12. Specific Populations No clinically significant differences in the pharmacokinetics of BESREMi were observed based on age, sex, body surface area, and JAK2V617F mutation.
Drug Interactions Clinical Studies No clinical studies evaluating the drug interaction potential of BESREMi have been conducted. In Vitro Studies In vitro studies indicate that BESREMi exhibited time-dependent inhibitory potential on CYP2A6. BESREMi did not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 in human liver microsomes.
BESREMi is not expected to induce CYP enzymes. However, interferon may influence CYP450 through modulating transcription factors and altering protein expression and/or structure. As this mechanism requires more time to exert effect, it cannot be evaluated by in vitro assays.
🧬 Pharmacodynamics ▾
12.2Pharmacodynamics The efficacy of ropeginterferon alfa-2b-njft is dependent on the stabilization of hematological parameters (hematocrit <45%, platelets <400 × 10 9 /L and leukocytes <10 × 10 9 /L). Pharmacokinetic-pharmacodynamic analyses have demonstrated that the reduction in the individual hematological parameters is dependent on ropeginterferon alfa-2b-njft concentrations. Complete hematological response (CHR, defined as a patient achieving hematocrit <45% without phlebotomy [at least 2 months since last phlebotomy], platelets ≤400 × 10 9 /L and leukocytes ≤10 × 10 9 /L) increased with increasing ropeginterferon alfa-2b-njft concentration over time.
Based on the exposure-response (E-R) analyses using data from the PEGINVERA study in patients with polycythemia vera, the predicted probability of CHR (95% Prediction Intervals) was 22% (11% – 34%) before treatment, 50% (38% – 62%) at week 20 (end of titration), 64% (47% – 78%) at week 52, and 70% (55% – 88%) at week 104. The E-R analyses show that the maximum probability of CHR is reached after 2 years of continuous treatment.
🔬 Clinical Studies ▾
14 CLINICAL STUDIES
14.1Essential Thrombocythemia SURPASS ET: The SURPASS ET study was a randomized, open-label, multicenter, active-controlled study to assess pharmacokinetics, efficacy, safety, and tolerability of BESREMi compared to anagrelide as second line therapy after 12 months of treatment. The study included 174 adults with essential thrombocythemia and documented resistance/intolerance to hydroxyurea, of which, 91 patients received BESREMi and 83 patients received anagrelide. The median age at baseline was 62.5 years (range 20-83 years), with 52% females and 48% males, and 96% Asian and 4% Caucasian patients.
There were 79% of patients with an ECOG Grade 0 and patients had a mean (SD) TSS of 12.5 (14) at baseline. Hydroxyurea was previously used by all patients, with an overall mean (SD) duration of use of 27.9 (59.7) months; the mean (SD) prior duration of use was 22 (39.9) months for patients who received BESREMi and 35.2 (80) months for patients who received anagrelide. There were 82% of patients with a JAK2V617F mutation at baseline, with a mean (SD) allelic burden of 44 (30)%.
There were 12% of patients with a CALR mutation at baseline, with a mean (SD) allelic burden of 25 (18)%. One percent of patients had an MPL mutation at baseline, with a mean (SD) allelic burden of 29 (4.1)%. At baseline, mean (SD) platelets and white blood cells were 1,024.5 × 10 9 /L (439.1) and 14.2 × 10 9 /L (7.7), respectively.
The spleen was palpable in 14% of patients at baseline, with a median spleen size of 13.9 cm. Two percent of patients had splenomegaly at baseline (defined as a longitudinal diameter of >17 cm). There were 35% of patients with a history of thrombosis, 35% of patients with a history of hemorrhage, 85% of patients with a JAK-2 mutation history, 9% of patients with a CALR mutation history, and 2% of patients with an MPL mutation history.
BESREMi was administered subcutaneously every 2 weeks at the starting dose of 250 mcg (Week 0), then 350 mcg (Week 2), and 500 mcg (Week 4), and then remained fixed at 500 mcg for the remaining Treatment Period. Anagrelide was administered orally; the starting dose, maintenance dose, and any dose adjustment was according to the local country product label and treatment practices. Low-dose aspirin (75 to 150 mg/day per local practice) was given to subjects in both arms during the 12 months of study treatment, unless contraindicated.
The median duration of treatment exposure was 11.9 months; 55% of patients completed at least 12 months of treatment and 36% of patients completed more than 12 months of treatment. Overall, 74% of patients completed the study, with 10% of patients discontinuing due to a study drug related treatment-emergent adverse event. The mean (SD) dose of BESREMi was 10,174.2 (3,120.3) mcg during the treatment period.
The efficacy of BESREMi was evaluated in the SURPASS ET study by assessing durable Modified European Leukemia Net (ELN) response rates at Months 9 and 12. The modified ELN response criteria involved the following: peripheral blood count remission (platelets ≤400 × 10 9 and white blood cells <9.5 × 10 9 /L) AND improvement or non-progression in disease-related signs (splenomegaly) AND absence of hemorrhagic or thrombotic events. The modified ELN response differs from the 2013 ELN response criteria as it excludes components for bone marrow histological remission and the requirement for durable resolution of disease-related signs and large symptoms improvement, and uses a lower white blood cell threshold.
Additional evaluations for efficacy included durable response at Months 3 and 6, longitudinal rate of change in the ELN response rates over 12 months, change from baseline in JAK2V617F allelic burden from baseline over time (by 2013 ELN criteria), and thromboembolic events. Other evaluations for efficacy included response rates based on peripheral blood count remission, no signs of progressive disease, and absence of any hemorrhagic or thrombotic event… [Excerpted — this section continues on DailyMed.]
🧪 Nonclinical Toxicology ▾
13 NONCLINICAL TOXICOLOGY
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Ropeginterferon alfa-2b-njft has not been tested for its carcinogenic potential. Neither ropeginterferon alfa-2b-njft nor its components, interferon or methoxypolyethylene glycol, caused damage to DNA when tested in the standard battery of mutagenesis assays. Ropeginterferon alfa-2b-njft effects on fertility have not been assessed [see Use in Specific Populations ( 8.1 , 8.2 , 8.3 )] .
📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ▾
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Ropeginterferon alfa-2b-njft has not been tested for its carcinogenic potential. Neither ropeginterferon alfa-2b-njft nor its components, interferon or methoxypolyethylene glycol, caused damage to DNA when tested in the standard battery of mutagenesis assays. Ropeginterferon alfa-2b-njft effects on fertility have not been assessed [see Use in Specific Populations ( 8.1 , 8.2 , 8.3 )] .
📖 Instructions for Use ▾
INSTRUCTIONS FOR USE BESREMi [bez-reh-me] (ropeginterferon alfa-2b-njft) injection, for subcutaneous use Single-dose prefilled syringe This "Instructions for Use" contains information on how to prepare and inject BESREMi under your skin (subcutaneous injection) using the single-dose prefilled syringe. Guide to Prefilled syringe and Needle Parts (Figure A) Storing BESREMi Store the BESREMi carton in the refrigerator between 36°F to 46°F (2°C to 8°C) (Figure B). • Keep your BESREMi prefilled syringes in their original carton (Figure B) while stored. • Do not freeze the prefilled syringes. • Do not use a prefilled syringe that has been frozen or left in direct sunlight. • Keep BESREMi prefilled syringes, needles, and all medicines out of the reach of children.
Important information you need to know before injecting BESREMi Read this Instructions for Use before using your single-dose BESREMi prefilled syringe for the first time and each time you get a new prescription. There may be new information. This leaflet does not take the place of talking with your healthcare provider about your medical condition or your treatment.
Ask your healthcare provider about the right way to prepare and give your BESREMi injection. • Your healthcare provider will tell you the prescribed dose that you should take and the right amount of BESREMi to measure in the prefilled syringe for your dose. Each time you inject, be sure that you know the prescribed dose of BESREMi to inject. Your dose may change over time. • BESREMi is for subcutaneous (under the skin) injection only. • BESREMi is for one-time use only.
Do not reuse your prefilled syringe or needle. • Do not use a prefilled syringe or needle that is damaged or broken. Contact your healthcare provider for a replacement prefilled syringe or additional needles. • Inject BESREMi into the top of the thighs or lower stomach-area just under the skin. Do not inject BESREMi into any other area of the body. • Throw away (dispose of) the BESREMi prefilled syringe with needle attached right away after use, even if there is medicine left in the prefilled syringe.
See Step 10 in the section " Dispose of used prefilled syringes and needles." Gather and check supplies 1. Prepare BESREMi Prefilled Syringe 1.1. Take the BESREMi carton out of the refrigerator (Figure E).
1.2. Check the expiration date ("EXP") on the top panel of the carton to make sure it has not passed (Figure F). Do not use the prefilled syringe if the expiration date has passed.
1.3. Let carton containing the BESREMi prefilled syringe sit on a clean work surface for 15 to 30 minutes to allow it to come to room temperature (Figure G). Do not warm the prefilled syringe any other way.
2. Gather supplies for injection 2.1. After allowing the prefilled syringe to come to room temperature for 15 to 30 minutes inside the carton, gather the following additional supplies.
Alcohol Swab (Figure H). FDA-cleared Sharps Disposal Container (Figure I) A paper towel, sink, or trash can to minimize mess during dose adjustment (Figure J). Optional Items: Gauze or Cotton Ball and a Small Adhesive Bandage (Figure K).
3. Wash hands and remove syringe from tray 3.1. Wash your hands with soap and water, then dry your hands (Figure L).
3.2. Open the carton and remove the clear plastic tray that holds the BESREMi prefilled syringe and needle package (Figure M). 3.3.
Remove the needle package and BESREMi prefilled syringe from the plastic tray. Hold the prefilled syringe by the middle of the syringe body during removal (Figure N). 4.
Check the liquid medicine in the BESREMi prefilled syringe 4.1. Check the liquid medicine in the prefilled syringe (Figure O). The liquid should be clear and colorless to slightly yellow, and should not have particles.
Do not use the prefilled syringe if the liquid is cloudy, discolored, or contains particles. Contact your healthcare provider or pharmacist. 4.2.
Check the syringe to see if it is damaged or broken (Figure O). Do not use if it… [Excerpted — this section continues on DailyMed.]
📄 Recent Major Changes ▾
Indications and Usage, Essential Thrombocythemia ( 1.1 ) 08/2026 Dosage and Administration ( 2.2 , 2.3 ) 08/2026 Dosage and Administration ( 2.4 ) 06/2026 Warnings and Precautions ( 5.1 , 5.2 , 5.3 , 5.4 , 5.9 , 5.10 , 5.11 ) 08/2026
📄 Package Label / Principal Display Panel ▾
PRINCIPAL DISPLAY PANEL - 500 mcg/mL Syringe Label BESREMi ® (ropeginterferon alfa-2b-njft) INJECTION 500 mcg/mL For Subcutaneous Use LOT: EXP: Rx Only PharmaEssentia Corp. PRINCIPAL DISPLAY PANEL - 500 mcg/mL Syringe Label
PRINCIPAL DISPLAY PANEL - 500 mcg/mL Syringe Carton BESREMi ® (ropeginterferon alfa-2b-njft) INJECTION 500 mcg/mL For Subcutaneous Use. Rx Only One Single-Dose Prefilled Syringe CAUTION: Prefilled syringe contains more medication than your prescribed dose. ATTENTION: Dispense the Enclosed Medication Guide to Each Patient.
NDC 73536-500-01 Contains: • One Single-Dose Prefilled Syringe • One Injection Needle • Full Prescribing Information • Instructions for Use • Medication Guide PharmaEssentia™ PRINCIPAL DISPLAY PANEL - 500 mcg/mL Syringe Carton
PRINCIPAL DISPLAY PANEL - 500 mcg/mL Cartridge Label LOT: NNDPL-BNNNA EXP: YYYY-MM BESREMI Pen TM (ropeginterferon alfa-2b-njft) INJECTION 500 mcg/0.5 mL For Subcutaneous Use Single-Dose Prefilled Pen Injector PharmaEssentia Corporation U.S. License No. 2155 Storage: Store in the refrigerator between 36°F to 46°F (2°C to 8°C) in the original carton to protect from light.
Do not freeze. Keep out of the reach of children. Rx Only PharmEssentia PRINCIPAL DISPLAY PANEL - 500 mcg/mL Cartridge Label
PRINCIPAL DISPLAY PANEL - 500 mcg/mL Cartridge Carton NDC 73536-511-01 BESREMi Pen TM (ropeginterferon alfa-2b-njft) INJECTION 500 mcg/0.5 mL For Subcutaneous Use One Single-Dose Prefilled Pen Injector. Discard unused portion. Dials in 50 mcg increments and contains 500 mcg total.
CAUTION: Prefilled pen injector may contain more medication than your prescribed dose. ATTENTION: Dispense the Enclosed Medication Guide to Each Patient. Contains: - One Single-Dose Prefilled Pen Injector - Full Prescribing Information - One Injection Needle - Instructions for Use - Medication Guide Rx Only PharmaEssentia PRINCIPAL DISPLAY PANEL - 500 mcg/mL Cartridge Carton PRINCIPAL DISPLAY PANEL - 500 mcg/mL Cartridge Carton
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| NDC identity (package / product / labeler codes) | ✓ Available |
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| Product & package description | ✓ Available |
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| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
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| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | ✓ Available |