How Reblozyl Reduces Transfusion Dependence in Hematology Treatments

1. How Reblozyl Reduces Transfusion Dependence in Hematology Treatments Understanding Anemia and Transfusion Burden in Hematology Anemia is one of the most common and challenging problems in blood disorders like β-thalassemia and myelodysplastic syndromes (MDS). It can cause tiredness, dizziness, shortness of breath, and a fast heartbeat, making everyday life difficult. Many patients eventually need regular red blood cell (RBC) transfusions, which can lead to iron overload and other health risks. With limited treatment options available, managing anemia is mostly about improving low blood counts, reducing the need for transfusions, and helping patients feel better overall.1-5 That’s where Reblozyl (luspatercept) steps in as an exciting new therapy for eligible adults, and RX4U is proud to support Indian patients in accessing this medicine safely and reliably. What Is Reblozyl; Active Compound and Mechanism Reblozyl (generic name: luspatercept) is a newer treatment option for people with certain types of anemia, especially those with low-risk myelodysplastic syndromes (LR- MDS) who do not have the del(5q) mutation and have not responded well to ESAs (erythropoiesis-stimulating agents like EPO or darbepoetin). Normally, the first step to treat anemia in MDS is with ESAs, which help boost red blood cell (RBC) production. These treatments work best when your body’s own EPO levels are low (usually under 200 U/L). But not everyone responds to ESAs, and even when they do, the effect may not last very long, especially for patients who have ring sideroblasts (RS), a specific type of MDS feature.4 When ESAs no longer work, the options become limited, especially for patients who don’t have the del(5q) gene mutation. That’s where Reblozyl (luspatercept) comes in. Reblozyl works differently. Instead of copying the body’s natural EPO, it targets a pathway in the bone marrow called the TGF-beta signaling pathway. In simple terms, this pathway can sometimes block your red blood cells from maturing properly. Reblozyl releases this block, helping immature red blood cells grow and become healthy, functioning ones. Think of it like removing the brakes on red blood cell production. 4

2. Because of this unique action, Reblozyl gives a new chance to patients who are relying on frequent blood transfusions and haven't responded to other treatments. It’s especially helpful in patients with ring sideroblasts or SF3B1 mutations, where standard therapies fall short. 4 How Reblozyl Stimulates Red Blood Cell Production Reblozyl works differently from ESAs. While ESAs mostly support early-stage red blood cell formation by encouraging immature cells to multiply, Reblozyl goes a step further. It targets a key pathway in the bone marrow known as the TGF-β (transforming growth factor beta) signaling pathway. In MDS, this pathway is often overactive, suppressing the maturation of red blood cells. Reblozyl acts by inhibiting this pathway, allowing immature red blood cells to continue maturing and become fully functional. 4 This makes it particularly effective in patients with MDS who have RS or SF3B1 mutations and who haven’t responded well to ESAs. In this group, Reblozyl helps reduce transfusion dependency by enhancing late-stage red blood cell development, an area where other treatments fall short.4 Clinical Use Cases in Reducing Transfusion Frequency Luspatercept is used to reduce how often certain patients with anemia need red blood cell transfusions. It’s approved for people with β-thalassemia who require regular transfusions and for adults with very low-to-intermediate risk myelodysplastic syndromes (MDS) who are ESA-naïve but need ongoing RBC support.5 In clinical trials, patients with ring sideroblasts or an SF3B1 mutation, features commonly seen in MDS, showed especially good responses.5 Reblozyl Administration and Dosage Protocols Reblozyl (luspatercept) is given as a subcutaneous injection once every 3 weeks. It comes in two vial strengths, 25 mg and 75 mg, as a white or off-white powder that must be mixed with sterile water before use. Before each dose, the patient’s hemoglobin level and transfusion history should be reviewed.5 For beta-thalassemia, treatment starts at 1 mg/kg, and the dose can be adjusted based on how the patient responds. If there’s no improvement in transfusion needs by week 9, or if serious side effects occur, treatment should be stopped. For MDS-related anemia, the starting dose is also 1 mg/kg, with careful adjustments allowed up to 1.75 mg/kg, but only every 6 weeks. If transfusion needs don’t decrease by week 9 at the highest dose, therapy should be discontinued.

3. When a dose exceeds 1.2 mL, it should be split into multiple injections at different sites, using new syringes and needles for each.5 Potential Side Effects and Safety Considerations These are usually mild to moderate and tend to occur more often during the early treatment cycles:5 •Fatigue •Headache •Muscle and joint pain (myalgia, arthralgia) •Dizziness or vertigo •Nausea, diarrhea •Cough, abdominal discomfort •Shortness of breath (dyspnea) •High blood pressure (hypertension) •Elevated uric acid levels (hyperuricemia) •Allergic reactions (hypersensitivity) Important to note: Reblozyl is not a replacement for blood transfusions. Monitoring Effectiveness: What Clinicians Should Track To make sure Reblozyl (luspatercept) is working safely and effectively, the doctor regularly checks:5 •Hemoglobin levels– to see how your red blood cells are responding •Liver function tests– including ALT and AST, to ensure your body is handling the medicine well If needed, the doctor may also check how much of the medicine is in your blood using special lab tests: 5 •ELISA test– a quick blood test that uses a small sample to measure the amount of Reblozyl •Western blot test–a more detailed test used to confirm the medicine’s presence in your system These checks help your doctor adjust your dose if needed and make sure you're staying safe throughout your treatment. 5

4. Accessing Reblozyl Through Named Patient Program in India Reblozyl isn’t yet readily available in all Indian pharmacies, but the RX4U team is committed to ensuring eligible patients can access it safely and reliably using India’s Named Patient Program (NPP). With doctor supervision and RX4U’s expertise, Indian patients with transfusion-dependent MDS or β-thalassemia can legally import Reblozyl and receive support at every step, from paperwork and import to ongoing care. Summary of Reblozyl’s Role in Hematologic Management For patients struggling with regular transfusions due to MDS or β-thalassemia, Reblozyl (luspatercept) provides a new lifeline. By boosting natural red blood cell production, it significantly lowers the transfusion burden and helps many patients reclaim better health and freedom.1-5Thanks to RX4U’s support, patients in India can access this breakthrough therapy safely, guided by their own hematology teams. FAQs About Reblozyl and Anemia Care What happens if I get a serious side effect while on Reblozyl? If a serious (Grade 3 or 4) reaction occurs, like severe bone pain, high uric acid, high blood pressure, or a strong allergic reaction, your doctor may pause or stop the treatment. In some cases, once the side effect settles, the treatment can be restarted at a lower dose.5 How will my doctor monitor me during treatment? Your doctor will regularly check your hemoglobin levels and liver enzymes (ALT and AST) to make sure your body is handling the medicine well. Your doctor will regularly check your hemoglobin levels and liver enzymes (ALT and AST) to make sure your body is handling the medicine well.5 Note: The information provided is for education purpose only and is subjected to prescribing information of the drug and the guidance of your treating physician. Always consult your health care provider before making any medical decision for starting your treatment. References: 1.Kang C, Syed YY. Luspatercept: A Review in Transfusion-Dependent Anaemia due to Myelodysplastic Syndromes or β-Thalassaemia. Drugs. 2021;81(8):945- 952. doi:10.1007/s40265-021-01527-9

5. 2.Tinsley-Vance SM, Davis M, Ajayi O. Role of Luspatercept in the Management of Lower-Risk Myelodysplastic Syndromes. J Adv Pract Oncol. 2023;14(1):82- 87. doi:10.6004/jadpro.2023.14.1.8 3.Platzbecker U, Santini V, Komrokji RS, et al. Long-term utilization and benefit of luspatercept in transfusion-dependent, erythropoiesis-stimulating agent- refractory or -intolerant patients with lower-risk myelodysplastic syndromes with ring sideroblasts. Leukemia. 2023;37(11):2314-2318. doi:10.1038/s41375- 023-02031-7 4.KubaschKubasch AS, Fenaux P, Platzbecker U. Development of luspatercept to treat ineffective erythropoiesis. Blood Adv. 2021;5(5):1565-1575. doi:10.1182/bloodadvances.2020002177 5.Patel B, Moosavi L. Luspatercept. [Updated 2024 Oct 14]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560635/