Besremi

Besremi is used to treat essential thrombocythemia or polycythemia vera in adults. It is an interferon alfa-2b injection administered subcutaneously every 2 weeks. It is not known if Besremi is safe and effective in children.

Besremi works by binding to interferon alfa receptors (IFNAR) in the bone marrow, activating JAK1 and TYK2 kinases and STAT proteins, which send signals that switch certain genes on and off, helping to control the overproduction of blood cells caused by essential thrombocythemia and polycythemia vera. The actions involved in the therapeutic effects of interferon alfa in these conditions are not fully understood.

In SURPASS ET (NCT04285086), a randomized study of 174 adults with essential thrombocythemia who had an inadequate response to or could not tolerate hydroxyurea, 37.4% of the 91 patients treated with Besremi achieved a durable response at both months 9 and 12, compared with 3.6% of the 83 patients treated with anagrelide. Response was based on blood count remission, improvement or non-progression of disease-related signs such as an enlarged spleen, and no bleeding or clotting events.

In PEGINVERA, a 7.5-year clinical trial of 51 polycythemia vera patients (NCT01193699), Besremi achieved a complete hematological response in 61% of patients, with a median time to response of 7.8 months. A hematological response based only on hematocrit, platelet, and white blood cell counts was achieved in 80% of patients. Over half of the patients (53%) completed at least 5 years of treatment.

Besremi (ropeginterferon alfa-2b) gained FDA approval for polycythemia vera on November 12, 2021, and for essential thrombocythemia on August 31, 2026.

See the Instructions for Use that come with your Besremi prescription for detailed instructions on how to prepare and inject a dose.

• Use Besremi exactly as your healthcare provider tells you to. Your healthcare provider will tell you how much to inject and when to inject it. Do not inject more than your prescribed dose.
• Do not inject more than 1 dose of Besremi every 2 weeks without talking to your healthcare provider.
• Besremi comes in a single-dose prefilled syringe and a single-dose prefilled pen injector.
• Besremi is given as an injection under your skin (subcutaneous injection).
• Besremi can be given by yourself, a caregiver, or a healthcare provider. If your healthcare provider decides that you or a caregiver may give your injections of Besremi at home, you should receive training on the right way to prepare and inject Besremi. Do not try to inject Besremi yourself until your healthcare provider has shown you how to give Besremi the right way.
• Do not reuse the Besremi single-dose prefilled syringe or the single-dose prefilled pen injector. They are for one-time use only.
• If you inject too much Besremi, call your healthcare provider or the Poison Help Line at 1-800-222-1222 right away.
• Your healthcare provider will do blood tests before you start treatment and regularly during treatment to monitor your essential thrombocythemia or polycythemia vera and to check you for side effects.

Besremi carries a Boxed Warning for risk of serious disorders.

Risk of serious disorders

Interferon alfa products, including Besremi, may cause or make worse fatal or life-threatening nervous system and mental health (neuropsychiatric), autoimmune, ischemic, and infectious disorders. Besremi can cause serious side effects that:

• may cause death, or
• may worsen certain serious diseases that you may already have.

Tell your healthcare provider right away if you have any of the symptoms listed below during treatment. If symptoms get worse or become severe and continue, your healthcare provider may tell you to stop taking Besremi permanently. These symptoms may go away in some people after they stop treatment.

Mental health problems, including depression and suicide

Besremi may cause you to develop mood or behavior problems that may get worse during treatment 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.

You, your caregiver, or family member should tell your healthcare provider or get medical help right away if you develop any of the following, especially if they are new, worse, or worry you:

• thoughts about suicide or dying
• suicide attempts
• new or worse depression
• new or worse anxiety
• feeling very agitated or restless
• panic attacks
• trouble sleeping (insomnia)
• new or worse irritability
• acting aggressive, being angry, or violent
• acting on dangerous impulses
• an extreme increase in activity or talking (mania)
• other unusual changes in behavior or mood.

If you have thoughts of hurting yourself or thoughts of suicide, stop using Besremi right away and get medical help right away.

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 their treatment. Tell your healthcare provider if you have any of the following symptoms:

• tiredness
• problems concentrating
• urinating more often than normal
• sensitivity to heat or cold temperature
• very thirsty
• weight changes
• increase in appetite
• 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 monitor you closely during treatment with Besremi if you have a history of heart problems or blood clots.

You should not use Besremi if you have:

• high blood pressure that is not controlled
• congestive heart failure
• a serious abnormal heart rhythm
• narrowing of the arteries to your heart
• certain types of chest pain (angina)
• 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:

• fast heart rate or abnormal heart beat
• trouble breathing or chest pain
• pain, swelling, or redness in the arms, legs, ankles, or feet
• tiredness
• sudden confusion
• numbness or weakness
• loss of coordination
• trouble speaking clearly
• sudden vision changes.

Monitoring

Call your healthcare provider right away if you get any of the symptoms listed above during treatment.

Before and during treatment, you will need to see your healthcare provider regularly and have blood tests to monitor your essential thrombocythemia or polycythemia vera and to check for side effects.

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 the ingredients in Besremi. Symptoms of a serious allergic reaction to alpha-interferon may include itching, swelling of your face, tongue, throat, trouble breathing, feeling dizzy or faint, and chest pain. See the end of this Medication Guide for a complete list of ingredients. Ask your healthcare provider if you are not sure.
• have certain types of liver problems (moderate or severe liver impairment)
• have or had a serious or untreated autoimmune disease
• have received an organ or stem cell transplant and take immunosuppressive medicines.

Talk to your healthcare provider before taking Besremi if you have any of these conditions.

Before using Besremi, tell your healthcare provider about all of your medical conditions, including if you:

• are being treated for a mental illness or had treatment in the past for any mental illness, including depression, and have had thoughts of hurting yourself or others
• have thyroid problems
• have diabetes
• have a condition that suppresses your immune system, such as cancer
• have or ever had any problems with your heart, including a heart attack or high blood pressure
• have or ever had bleeding problems or a blood clot
• have liver problems
• have kidney problems
• are pregnant or plan to become pregnant. Besremi can harm your unborn baby and can cause loss of your pregnancy (miscarriage). Your healthcare provider should do a pregnancy test before you start treatment with Besremi. Use effective birth control (contraception) during treatment and for at least 8 weeks after your final dose. Talk to your healthcare provider about birth control choices for you during treatment with Besremi. Besremi can affect your menstrual cycles and may cause your menstrual periods to stop. Tell your healthcare provider if you become pregnant during treatment with Besremi.
• are breastfeeding or plan to breastfeed. It is not known if Besremi passes into your breast milk. You should not breastfeed during treatment and for 8 weeks after your final dose of Besremi.

Common side effects

The most common side effects of Besremi in adults with essential thrombocythemia are:

• increased liver function tests
• low red blood cell counts (anemia)
• fever
• increased protein in the urine
• bacterial infection
• itching
• weight loss.

The most common side effects of Besremi in adults with polycythemia vera are:

• flu-like symptoms
• joint pain
• tiredness
• itching
• runny or stuffy nose, cough, or sore throat
• muscle and bone pain.

Serious side effects

In addition to the side effects listed in the Important information above, Besremi can cause the following other serious side effects:

Decreased blood cell counts and bleeding problems. Besremi can cause decreased blood cell counts, including decreased platelets, red blood cells, or white blood cells, that can sometimes be severe. If your blood cell counts are low, you can develop anemia, serious infections, or have problems with bleeding or bruising. Your healthcare provider will monitor you for signs of infection or bleeding.

Tell your healthcare provider or get medical help right away if you develop any of the following symptoms:

• weakness and tiredness
• chills
• bruising easily
• burning and painful urination
• you have nose bleeds often
• urinating often
• fever
• coughing up yellow or pink mucus (phlegm)
• gum or tongue bleeding
• bleeding in the eye.

Serious allergic reactions and skin reactions. Besremi can cause serious, sudden allergic reactions. Stop using Besremi and get medical help right away if you get any of the following symptoms:

• skin rash or hives
• itching swelling of your face, eyes, lips, tongue, or throat
• trouble breathing
• chest pain
• feeling dizzy or faint.

Inflammation of the pancreas (pancreatitis). Tell your healthcare provider if you develop signs and symptoms of pancreatitis, including:

• nausea
• vomiting
• upper stomach area (abdomen) pain
• bloating
• fever.

Inflammation of the intestine (colitis). Besremi can cause serious and possibly life-threatening colitis. This can lead to open sores, bleeding, or reduced blood flow to the intestine. Tell your healthcare provider if you develop any signs or symptoms of colitis, including:

• stomach area (abdomen) pain
• bloody diarrhea or blood in your stool
• fever.

Lung problems. Besremi can cause serious and life-threatening lung problems that can lead to breathing problems (respiratory failure) or death. Tell your healthcare provider if you develop any signs or symptoms of a lung problem, including:

• shortness of breath
• cough
• difficulty breathing.

Eye problems. Besremi can cause severe eye problems with your retina that can lead to vision loss or blindness. You should have an eye exam before and during treatment with Besremi if you have diabetes or high blood pressure. Your healthcare provider may stop Besremi if you develop new or worsening eye problems during treatment. Tell your healthcare provider if you develop any new or worsening eye symptoms or vision changes during treatment, including:

• blurred vision
• dry eyes
• seeing floaters or flashes of light
• sudden loss of vision
• eye pain or redness.

High cholesterol and triglycerides (fats in the blood). Besremi can cause high levels of cholesterol and fats (triglycerides) in your blood. High triglyceride levels may lead to inflammation of the pancreas (pancreatitis). Your healthcare provider may treat high cholesterol or triglyceride levels.

Liver problems. Besremi can cause increases in liver enzymes and liver damage. Your healthcare provider should do blood tests to monitor your liver enzymes and liver function before you start and during treatment. Tell your healthcare provider if you develop any signs and symptoms of a liver problem, including:

• yellowing of your skin or the white part of your eyes
• swelling of your stomach area (abdomen)
• stomach area (abdomen) pain or discomfort
• confusion
• sleepiness
• nausea
• loss of appetite
• tiredness
• diarrhea
• bleeding more easily than normal.

Kidney problems. Your healthcare provider will do blood tests to check your kidney function before starting and during treatment with Besremi. Tell your healthcare provider if you develop any symptoms of a kidney problem, including:

• changes in the amount or color of your urine
• blood in your urine
• swelling in your ankles
• loss of appetite.

Your healthcare provider may stop Besremi if you develop severe kidney problems.

Tooth and gum (periodontal) problems. Besremi can cause tooth and gum problems, which can lead to tooth loss. Besremi can also cause problems with dry mouth that can damage your teeth and the lining of the mouth during long-term treatment. It is important to brush and floss your teeth well and have regular dental examinations during treatment with Besremi.

Skin problems. Get medical help if you develop any signs and symptoms of a skin problem during treatment with Besremi, including:

• itching
• hair loss
• rash
• redness
• dry skin
• a skin condition causing red, scaly patches (psoriasis)
• acne
• thickening of the skin
• excessive sweating.

Your healthcare provider may reduce your dose, temporarily stop, or permanently stop your treatment with Besremi if you develop side effects.

These are not all of the possible side effects of Besremi. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Adult dose of Besremi for essential thrombocythemia

• Starting dose: 250 mcg subcutaneously.
• At 2 weeks: increase to 350 mcg subcutaneously.
• At 4 weeks: increase to the maintenance dose of 500 mcg subcutaneously every 2 weeks.
• Maintain an every 2-week schedule throughout treatment unless dose modification is required for safety or tolerability.
• Monitor complete blood counts every 2 weeks during titration and every 3 to 6 months during maintenance.

Adult dose of Besremi for polycythemia vera

Patients not already on hydroxyurea:

• Initial: 100 mcg subcutaneously every 2 weeks.
• Titration: increase the dose by 50 mcg every 2 weeks (up to a maximum of 500 mcg) until hematological parameters are stabilized.

Patients transitioning from hydroxyurea:

• Start Besremi at 50 mcg subcutaneously every 2 weeks in combination with hydroxyurea.
• Gradually taper off the hydroxyurea by reducing the total biweekly dose by 20% to 40% every 2 weeks during weeks 3 to 12, and discontinue hydroxyurea by week 13.
• Increase the Besremi dose by 50 mcg every 2 weeks (up to a maximum of 500 mcg) until hematological parameters are stabilized.

For both groups, maintain the 2-week dosing interval until hematological stability is achieved for at least 1 year. After at least 1 year of hematological stability on a stable dose, the dosing interval may be expanded to every 4 weeks.

Interrupt or discontinue dosing if certain adverse reactions continue.

Besremi may cause neurologic symptoms, including dizziness, sleepiness, and hallucinations. Avoid driving or using heavy machinery if you develop any of these neurologic symptoms during treatment.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Besremi and certain other medicines may interact and cause side effects. Especially tell your healthcare provider if you take:

• Medicines broken down by CYP450 liver enzymes that have a narrow therapeutic index (narrow dose range), such as warfarin or phenytoin. Your doctor may need to adjust your dose.
• Myelosuppressive agents, such as chemotherapy medications. These may increase the risk of low blood cell counts.
• Narcotics, sleeping pills (hypnotics), or sedatives, such as diazepam, lorazepam, morphine, or codeine. These may cause excessive drowsiness, confusion, or serious effects on your brain and nervous system.

Know the medicines you take. Keep a list of your medicines and show it to your healthcare provider and pharmacist when you get a new medicine.

Store Besremi in the refrigerator between 36° F and 46° F (2° C and 8° C).

• Keep Besremi away from heat.
• Do not freeze Besremi.
• Keep the Besremi prefilled syringe or prefilled pen injector in the original carton to protect it from light.

Keep all medicines out of the reach of children and pets.

Active ingredient: ropeginterferon alfa-2b-njft

Inactive ingredients: benzyl alcohol, glacial acetic acid, polysorbate 80, sodium acetate, sodium chloride, Water for Injection.

Besremi is supplied as:

• Prefilled single-dose syringe: 500 mcg/mL in a single-dose prefilled syringe (NDC 73536-500-01)
• Prefilled single-dose pen injector: 500 mcg/0.5 mL in a single-dose prefilled pen injector (NDC 73536-511-01). The prefilled pen injector delivers Besremi in 50 mcg increments.

Besremi is manufactured by PharmaEssentia Corporation, 13F, No. 3, Park Street, Nangang District, Taipei 115, Taiwan, and distributed by PharmaEssentia USA Corporation, 35 Corporate Dr, Suite 325, Burlington, MA 01803, USA.