Rytelo

Rytelo (imetelstat) is an injectable telomerase inhibitor that may be used to treat adults with low- to intermediate-1 risk myelodysplastic syndromes (MDS) with transfusion-dependent anemia.

• Rytelo offers the potential for more than 24 weeks of freedom from red blood cell transfusions or anemia symptoms.

Rytelo works by binding to and inhibiting the activity of an enzyme telomerase which prevents telomere binding. Treatment with Rytelo reduces telomere length, the number of malignant stem and progenitor cells, and causes cell death. Rytelo is usually given as a 2-hour infusion into a vein every 4 weeks.

Rytelo was FDA-approved on 6 June 2024, making it the first telomerase inhibitor to be approved.

Rytelo may be used to treat low- to intermediate-1 risk myelodysplastic syndromes (MDS) in adults:

• with anemia (low red blood cell counts) who need blood transfusions of 4 or more red blood cell units over 8 weeks and
• who have not responded to, have stopped responding to, or cannot be treated with other medicines called erythropoiesis-stimulating agents (ESAs).

It is not known if Rytelo is safe and effective in children

Rytelo is administered as an intravenous infusion into your vein over 2 hours by a healthcare provider.

• It is usually given every 4 weeks.

Before treatment, your healthcare provider will administer the following pretreatment medications to prevent or reduce potential infusion-related reactions and will monitor you for at least 1 hour after the infusion for side effects.

• An antihistamine such as diphenhydramine 25 mg to 50 mg, intravenously or orally
• A corticosteroid such as hydrocortisone (or equivalent) 100 mg to 200 mg, intravenously or orally

During treatment, your healthcare provider will do blood tests to check for side effects and response.

How long you stay on treatment depends on how well you tolerate Rytelo and how effectively you respond to it. It is recommended that Rytelo be discontinued if you do not experience a decrease in the need for red blood cells (RBC) transfusion after 24 weeks of treatment (6 doses) or if unacceptable toxicity occurs.

Before receiving Rytelo, tell your healthcare provider about all of your medical conditions, including if you:

• are pregnant or plan to become pregnant
• are breastfeeding or plan to breastfeed

Pregnancy

Rytelo may harm your unborn baby and may cause loss of pregnancy (miscarriage). Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment.

Females who can become pregnant:

• your healthcare provider will perform a pregnancy test before you are given Rytelo.
• you should use effective birth control (contraception) during treatment with Rytelo and for 1 week after your last dose.

Breastfeeding

It is not known if Rytelo passes into breast milk. Do not breastfeed during treatment with Rytelo and for 1 week after your last dose.

The most common side effects of Rytelo include:

• decreased platelet counts
• decreased white blood cell counts, including decreased neutrophils
• increased liver enzymes (AST, alkaline phosphatase, and ALT)
• fatigue/tiredness
• longer than usual blood clotting times
• joint, bone, and muscle pain
• Covid-19 infections
• headache.

Rytelo may cause fertility problems in females. This could affect your ability to get pregnant. Talk to your healthcare provider if this is a concern for you.

Serious side effects and warnings

Rytelo may cause serious side effects, including:

Low platelet counts (thrombocytopenia). These are common during treatment with Rytelo and can also be severe and increase your risk for bleeding. Your healthcare provider may give you platelet transfusions to reduce the risk of bleeding if you develop a low platelet count during treatment. Tell your healthcare provider right away if you develop any signs or symptoms of bleeding, including:

• unusual bleeding or bruising
• bleeding that lasts a long time
• nosebleeds
• vomiting blood
• blood in your stools or black tarry stools.

Low neutrophil counts (neutropenia). Neutrophils are a type of white blood cell that helps fight infection. Low neutrophil counts (neutropenia) can increase the risk of serious infections. Your doctor may prescribe medications to prevent or treat neutropenia during treatment with Rytelo. Tell your healthcare provider right away if you develop any signs or symptoms of infection during treatment, including fever, shortness of breath or trouble breathing, cough, chills, or pain or burning when you urinate.

• Before, during, and after starting Rytelo, your doctor will regularly check your blood platelet and neutrophil counts. If these counts become too low (thrombocytopenia or neutropenia), your treatment may be delayed, reduced in dose, or stopped.

Infusion-related reactions that can be severe and may cause a sudden increase in blood pressure (called a hypertensive crisis). To prevent or reduce infusion-related reactions, your doctor will give you medication before each Rytelo infusion and monitor you for an hour afterward. If you experience a reaction, the infusion may be slowed down, paused, or stopped permanently. Tell your healthcare provider if you develop any signs or symptoms of infusion-related reactions, including stomach pain, joint pain, weakness or fatigue, back and bone pain, diarrhea, redness, headache, high blood pressure, not feeling well, chest pain that is not related to your heart. itching, or hives.

Rytelo may cause harm to an unborn baby. Females with the ability to have children should use effective contraception.

It is not known if Rytelo is safe and effective in children.

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

• The dosage of Rytelo depends on your weight but is calculated at 7.1 mg/kg.
• Your healthcare provider will prescribe a dose that is right for you and may change your dose or dosing schedule depending on how you respond.

Tell your healthcare provider about all your medicines, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Know the medicines you take. Keep a list to show your healthcare provider and pharmacist when you get a new medicine.

There are no specific drug-drug interactions listed in the Rytelo package insert, however, drug interaction studies have found Rytelo is not an inhibitor or inducer of CYP450 enzymes, but is an inhibitor of OATP1B1 and OATP1B3.

Refer to the latest package insert for more information about drug interactions.

Store vials of Rytelo in the refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton. Do not freeze.

Once diluted, preferably use immediately, or within:

• 18 hours from the time of reconstitution when stored at room temperature 20°C to 25°C (68°F to 77°F)
• 48 hours from the time of reconstitution when stored refrigerated at 2°C to 8°C (36°F to 46°F).

Patheon Italia (47 mg vials) and Catalent Indiana (188 mg vials) make Rytelo for Geron Corporation.

Rytelo 47 mg dose

Active ingredients: Imetelstat 47 mg (equivalent to 50 mg imetelstat sodium).

Inactive ingredients: sodium carbonate anhydrous or hydrochloric acid may be added during manufacturing to adjust the pH.

Contains no preservatives.

Rytelo 188 mg dose

Active ingredients: Imetelstat 188 mg (equivalent to 200 mg imetelstat sodium).

Inactive ingredients: sodium carbonate monohydrate or hydrochloric acid may be added during manufacturing to adjust the pH.

Contains no preservatives.