Rytelo

imetelstat sodium · Injection, Powder, Lyophilized, For Solution · Intravenous

Prescription (Rx) Oligonucleotide Telomerase Inhibitor

Uses

1. INDICATIONS AND USAGE RYTELO is indicated for the treatment of adult patients with low- to intermediate-1 risk myelodysplastic syndromes (MDS) with transfusion-dependent anemia requiring 4 or more red blood cell units over 8 weeks who have not responded to or have lost response to or are ineligible for erythropoiesis-stimulating agents (ESA). RYTELO is an oligonucleotide telomerase inhibitor indicated for the treatment of adult patients with low- to intermediate-1 risk myelodysplastic syndromes (MDS) with transfusion-dependent anemia requiring 4 or more red blood cell units over 8 weeks who have not responded to or have lost response to or are ineligible for erythropoiesis-stimulating agents (ESA). ( 1 )

Dosage and administration

2. DOSAGE AND ADMINISTRATION The recommended dosage of RYTELO is 7.1 mg/kg administered as an intravenous infusion over 2 hours every 4 weeks. ( 2.1 ) Premedicate prior to dosing with RYTELO for potential infusion-related reactions. ( 2.2 ) See full prescribing information for preparation and administration instructions. ( 2.4 ) 2.1. Recommended Dosage The recommended dosage of RYTELO is 7.1 mg/kg administered as an intravenous infusion over 2 hours every 4 weeks. Discontinue RYTELO if a patient does not experience a decrease in red blood cell (RBC) transfusion burden after 24 weeks of treatment (administration of 6 doses) or if unacceptable toxicity occurs at any time [see Dosage and Administration (2.3) ] . 2.2. Recommended Premedications Administer the following pre-treatment medications at least 30 minutes prior to dosing to prevent or reduce potential infusion-related reactions: diphenhydramine (or equivalent) 25 mg to 50 mg, intravenously or orally hydrocortisone (or equivalent) 100 mg to 200 mg, intravenously or orally Monitor patients for adverse reactions for at least one hour after the infusion has been completed [see Warnings and Precautions (5.3) and Adverse Reactions (6.1) ] . 2.3. Dosage Modifications for Adverse Reactions Recommended dose reductions for Grade 3 and Grade 4 adverse reactions are found in Table 1. The management of Grade 3 and Grade 4 adverse reactions may require temporary dose delay, dose reduction, or treatment discontinuation and are presented in Table 2 and Table 3. RYTELO treatment should be permanently discontinued if the patient cannot tolerate the lowest dose level of 4.4 mg/kg. Table 1: Recommended Dose Reduction for RYTELO for Grade 3 and Grade 4 Adverse Reactions Dose Reduction Dose Every 4 Weeks First dose reduction 5.6 mg/kg Second dose reduction 4.4 mg/kg Dosage Modifications for Hematologic (Grade 3 and Grade 4) Adverse Reactions Monitor complete blood cell counts prior to administration of RYTELO, weekly for the first two cycles, prior to each cycle thereafter, and as clinically indicated. Delay the next cycle if absolute neutrophil count is less than 1 × 10 9 /L or platelets are less than 50 × 10 9 /L. Modify dose as described in Table 2. Table 2: Dosage Modifications for Patients with Hematologic Adverse Reactions (Grade 3 and Grade 4) Adverse Reaction Severity Grade Severity based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03. Occurrence Treatment Modification Abbreviation: ANC = absolute neutrophil count Thrombocytopenia [see Warnings and Precautions (5.1) ] Grade 3 First Delay RYTELO until recovery of platelets to 50 × 10 9 /L; restart at same dose level. Second and Third Delay RYTELO until recovery of platelets to 50 × 10 9 /L; restart at one dose level lower. Fourth Discontinue RYTELO. Grade 4 First and Second Delay RYTELO until recovery of platelets to 50 × 10 9 /L; restart at one dose level lower. Third Discontinue RYTELO. Neutropenia [see Warnings and Precautions (5.2) ] Grade 3 First Delay RYTELO until recovery of ANC to 1 × 10 9 /L; restart at same dose level. Second and Third Delay RYTELO until recovery of ANC to 1 × 10 9 /L; restart at one dose level lower. Fourth Discontinue RYTELO. Grade 4 First and Second Delay RYTELO until recovery of ANC to 1 × 10 9 /L; restart at one dose level lower. Third Discontinue RYTELO. Dosage Modifications for Non-hematologic Adverse Reactions Dosage modifications for infusion-related reactions and other adverse drug reactions, including elevated liver function tests (LFTs), are described in Table 3. Monitor liver function tests prior to administration of RYTELO, weekly for the first cycle, prior to each cycle thereafter, and as clinically indicated. Table 3: Dosage Modifications for Patients with Non-hematologic Adverse Reactions Adverse Reaction Severity Grade Severity based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03. Occurrence Treatment Modification Abbreviation: LFT = liver function test Infusion-Related Reactions [see Warnings and Precautions (5.3) ] Grade 2 or 3 First and Second Interrupt the RYTELO infusion until resolution of the adverse reaction or until the intensity of the reaction decreases to Grade 1; restart infusion at 50% of the infusion rate administered prior to the adverse reaction. Third For Grade 2, stop infusion. May restart at next cycle. For Grade 3, permanently discontinue RYTELO. Grade 4 First Stop infusion, administer supportive care as appropriate and permanently discontinue RYTELO. Other adverse reactions including elevated LFTs [see Adverse Reactions (6.1) ] Grade 3 or 4 First and Second Delay RYTELO until recovery of adverse reactions to Grade 1 or baseline; restart at one dose level lower. Third Permanently discontinue RYTELO. 2.4. Preparation and Administration RYTELO is provided as a lyophilized powder in a single-dose vial for intravenous infusion only and must be reconstituted and diluted prior to administration. Use aseptic technique to prepare RYTELO. RYTELO does not contain a preservative. Reconstitution: Calculate the dose of RYTELO needed based on the patient's body weight (kg). Determine the number of RYTELO vials needed to achieve the required dose (total mg) per Table 4. More than one vial may be needed to achieve a full dose. Remove the RYTELO vials from the refrigerator and allow the vials to sit for 10 minutes to 15 minutes (not to exceed 30 minutes) to adjust to room temperature 20°C to 25°C (68°F to 77°F) before use. Reconstitute each vial of RYTELO with the volume of 0.9% Sodium Chloride Injection provided in Table 4 directly onto the lyophilized powder to obtain a concentration of 31.4 mg/mL of imetelstat. Table 4: Reconstitution Volumes Strength Recommended to use the appropriate combination of vial strengths to most closely match the intended dose based on the patient's weight.

Dosage forms and strengths

3. DOSAGE FORMS AND STRENGTHS For injection: 47 mg of imetelstat supplied as a white to off-white or slightly yellow lyophilized powder in a single-dose vial for reconstitution. For injection: 188 mg of imetelstat supplied as a white to off-white or slightly yellow lyophilized powder in a single-dose vial for reconstitution. For injection: 47 mg powder in a single-dose vial for reconstitution. ( 3 ) For injection: 188 mg powder in a single-dose vial for reconstitution. ( 3 )

Contraindications

4. CONTRAINDICATIONS None. None. ( 4 )

Warnings and precautions

5. WARNINGS AND PRECAUTIONS Thrombocytopenia : Grade 3 and Grade 4 thrombocytopenia occurred; obtain complete blood cell counts prior to initiation of RYTELO, weekly for the first two cycles, and prior to each cycle thereafter to monitor. Delay or dose reduce as recommended. ( 2.3 , 5.1 ) Neutropenia : Grade 3 and Grade 4 neutropenia occurred; obtain complete blood cell counts prior to initiation of RYTELO, weekly for the first two cycles, and prior to each cycle thereafter to monitor. Delay or dose reduce as recommended. ( 2.3 , 5.2 ) Infusion-Related Reactions : Premedicate before infusion. Interrupt, decrease the rate of infusion, or permanently discontinue RYTELO based on severity. ( 2.2 , 2.3 , 5.3 ) Embryo-Fetal Toxicity : Can cause embryo-fetal harm. Advise females of reproductive potential of potential risk to a fetus and to use effective contraception. ( 5.4 , 8.1 , 8.3 ) 5.1. Thrombocytopenia RYTELO can cause thrombocytopenia based on laboratory values. In the clinical trial, new or worsening Grade 3 or 4 decreased platelets occurred in 65% of patients with MDS treated with RYTELO [see Adverse Reactions (6.1) ] . Median time to onset of first occurrence of Grade 3 or 4 decreased platelets was 6 weeks (range: 2 to 88 weeks) and median time to recovery from each occurrence of Grade 3 or 4 decreased platelets to Grade 2 or lower, or last value available, was 1.3 weeks (range: 0.1 to 13 weeks). Grade 3 or 4 decreased platelets occurred throughout treatment with RYTELO, with 48% of patients experiencing Grade 3 or Grade 4 thrombocytopenia during cycles 1-3, 31% during cycles 4-6, 33% during cycles 7-12, and 24% during cycles 13 and beyond. Grade 3 or 4 bleeding was seen in 2.5% of patients, including gastrointestinal bleeding (1.7%) and hematuria (0.8%). Monitor patients with thrombocytopenia for bleeding. Monitor complete blood cell counts prior to initiation of RYTELO, weekly for the first two cycles, prior to each cycle thereafter, and as clinically indicated. Administer platelet transfusions as appropriate. Delay the next cycle and resume at the same or reduced dose, or discontinue as recommended [see Dosage and Administration (2.3) ] . 5.2. Neutropenia RYTELO can cause neutropenia based on laboratory values. In the clinical trial, new or worsening Grade 3 or 4 decreased neutrophils occurred in 72% of patients with MDS treated with RYTELO [see Adverse Reactions (6.1) ] . Median time to onset of first occurrence of Grade 3 or 4 decreased neutrophils was 4.6 weeks (range: 1 to 81 weeks) and median time to recovery from each occurrence of Grade 3 or 4 decreased neutrophils to Grade 2 or lower, or last value available, was 1.9 weeks (range: 0 to 16 weeks). Grade 3 or 4 decreased neutrophils occurred throughout treatment with RYTELO, with 65% of patients experiencing Grade 3 or Grade 4 neutropenia during cycles 1-3, 35% during cycles 4-6, 32% during cycles 7-12, and 39% during cycles 13 and beyond. Febrile neutropenia occurred in 0.8% and sepsis in 4.2%. Monitor patients with Grade 3 or 4 neutropenia for infections, including sepsis. Monitor complete blood cell counts prior to initiation of RYTELO, weekly for the first two cycles, prior to each cycle thereafter, and as clinically indicated. Administer growth factors and anti-infective therapies for treatment or prophylaxis as appropriate. Delay the next cycle and resume at the same or reduced dose, or discontinue as recommended [see Dosage and Administration (2.3) ] . 5.3. Infusion-Related Reactions RYTELO can cause infusion-related reactions. In the clinical trial, infusion-related reactions occurred in 8% of patients with MDS treated with RYTELO; Grade 3 or 4 infusion-related reactions occurred in 1.7%, including hypertensive crisis (0.8%). The most common infusion-related reaction was headache (4.2%). Infusion-related reactions usually occur during or shortly after the end of the infusion. Premedicate patients at least 30 minutes prior to infusion with diphenhydramine and hydrocortisone as recommended and monitor patients for at least one hour following the infusion as recommended [see Dosage and Administration (2.2) ]. Manage symptoms of infusion-related reactions with supportive care and infusion interruptions, decrease infusion rate, or permanently discontinue as recommended [see Dosage and Administration (2.3) ] . 5.4. Embryo-Fetal Toxicity Based on findings in animals, RYTELO can cause embryo-fetal harm when administered to a pregnant woman. In animal reproduction studies, administration of imetelstat to pregnant mice during the period of organogenesis resulted in embryo-fetal mortality at maternal exposures (AUC) 2.5-times the human exposure at the recommended clinical dose. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with RYTELO and for 1 week after the last dose [see Use in Specific Populations (8.1 , 8.3) ] .

Side effects

6. ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Thrombocytopenia [see Warnings and Precautions (5.1) ] Neutropenia [see Warnings and Precautions (5.2) ] Infusion-Related Reactions [see Warnings and Precautions (5.3) ] Most common adverse reactions (incidence ≥10% with a difference between arms of >5% compared to placebo), including laboratory abnormalities are decreased platelets, decreased white blood cells, decreased neutrophils, increased AST, increased alkaline phosphatase, increased ALT, fatigue, prolonged partial thromboplastin time, arthralgia/myalgia, COVID-19 infections, and headache. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Geron Corporation at 1-855-437-6664 (1-855-GERONMI) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1. Clinical 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. Low- to Intermediate-Risk Myelodysplastic Syndromes The safety of RYTELO was evaluated in a randomized, double-blind, placebo-controlled, multicenter trial (IMerge) in 177 adult patients with International Prognostic Scoring System (IPSS) low- to intermediate-1 risk MDS who were transfusion-dependent and relapsed or refractory to or ineligible for ESA treatment [see Clinical Studies (14) ] . The safety population included patients who received at least one dose of either RYTELO (n=118) or placebo (n=59) at 7.1 mg/kg as an intravenous infusion administered over two hours every 4 weeks. The median time on treatment with RYTELO was 8 months (range, 0 to 38 months); 69% of patients were exposed to RYTELO for 24 weeks or longer and 45% were exposed for 48 weeks or longer. The median age of patients who received at least one dose of RYTELO was 72 years (range: 44 to 87 years) with 77% of patients 65 years of age and older and 30% of patients 75 years of age and older. Participants were 60% male, 81% White, 7% Asian, and 0.8% Black. Serious adverse reactions occurred in 32% of patients who received RYTELO. Serious adverse reactions in > 2% of patients included sepsis (4.2%), fracture (3.4%), cardiac failure (2.5%), and hemorrhage (2.5%). Fatal adverse reactions occurred in 0.8% of patients who received RYTELO, including sepsis (0.8%). Permanent discontinuation of RYTELO due to an adverse reaction occurred in 15% of patients. Adverse reactions which resulted in permanent discontinuation of RYTELO in > 2% of patients included neutropenia and thrombocytopenia. Dosage interruptions of RYTELO due to an adverse reaction occurred in 80% of patients. Adverse reactions which required dosage interruption in > 5% of patients included neutropenia, thrombocytopenia and infections. Dose reductions of RYTELO due to an adverse reaction occurred in 49% of patients. Adverse reactions which required dose reductions in > 2% of patients included neutropenia and thrombocytopenia. The most common (≥10% with a difference between arms of >5% compared to placebo) adverse reactions, including laboratory abnormalities, were decreased platelets, decreased white blood cells, decreased neutrophils, increased AST, increased alkaline phosphatase, increased ALT, fatigue, prolonged partial thromboplastin time, arthralgia/myalgia, COVID-19 infections, and headache. Table 5 summarizes the adverse reactions in IMerge. Table 5: Adverse Reactions (≥5%) in Patients with MDS Who Received RYTELO with a Difference Between Arms of >2% Compared to Placebo in IMerge Adverse Reaction RYTELO (N=118) Placebo (N=59) All Grades % Grades 3 or 4 % All Grades % Grades 3 or 4 % Graded according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03. General disorders and administrative site conditions Fatigue Fatigue: asthenia, fatigue, and malaise. 29 0 20 3.4 Musculoskeletal and connective tissue disorders Arthralgia/myalgia Arthralgia/myalgia: arthralgia, back pain, bone pain, musculoskeletal pain, myalgia, neck pain, non-cardiac chest pain, pain, pain in extremity, pain in jaw, and pelvic pain. 25 2.5 19 5 Infections and infestations COVID-19 COVID-19: asymptomatic COVID-19, COVID-19, COVID-19 pneumonia, and SARS-CoV-2 antibody test positive. 19 1.7 14 5 Urinary tract infection Urinary tract infection: cystitis, Escherichia urinary tract infection, renal abscess, and urinary tract infection. 9 2.5 7 0 Nervous system disorders Headache 13 0.8 5 0 Syncope Syncope: fall, pre-syncope, and syncope. 7 1.7 1.7 0 Immune system disorders Infusion-related reactions Infusion-related reactions: abdominal pain, arthralgia, asthenia, back pain, bone pain, diarrhea, erythema, headache, hypertensive crisis, malaise, non-cardiac chest pain, pruritus, and urticaria. Only events considered related to infusion-related reactions are included. 8 1.7 3.4 0 Respiratory, thoracic and mediastinal disorders Epistaxis 7 0 0 0 Vascular disorders Hematoma 6 0 0 0 Skin and subcutaneous tissue disorders Pruritus 6 0 1.7 0 Cardiac disorders Atrial arrhythmia Atrial arrhythmia: atrial fibrillation and atrial flutter. 6 1.7 3.4 1.7 Injury, poisoning and procedural complications Fractures Fractures: femur fracture, hand fracture, hip fracture, humerus fracture, lumbar vertebral fracture, and thoracic vertebral fracture. 5 3.4 1.7 1.7 Clinically relevant adverse reactions in < 5% of patients who received RYTELO included febrile neutropenia, sepsis, gastrointestinal hemorrhage, and hypertension. Table 6 summarizes the laboratory abnormalities in IMerge.

Use in specific populations

8. USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed. ( 8.2 ) 8.1. Pregnancy Risk Summary Based on findings in animal studies, RYTELO can cause embryo-fetal harm when administered to a pregnant woman. There are no available data on RYTELO use in pregnant women to evaluate for drug-associated risk. In embryo-fetal developmental toxicity studies, administration of imetelstat to pregnant mice and rabbits during the period of organogenesis resulted in embryo-fetal mortality, which in mice occurred at maternal exposures approximately 2.5 times the human exposure at the recommended clinical dose. Advise pregnant women of the potential risk to a fetus [see Data ] . In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In embryo-fetal developmental toxicity studies, imetelstat was administered by IV bolus injection at doses of 4.7, 9.4, 14.1 or 28.2 mg/kg/day on gestation days 6, 9, and 12 in mice, or by 2-hour intravenous infusion at doses of 4.7, 14.1, or 28.2 mg/kg on gestation days 6 and 13 in rabbits. In rabbits, the dose of 28.2 mg/kg was maternally toxic. Increased post-implantation loss due to an increase in early resorptions, resulting in a decrease in viable fetuses and litter was noted in mice at 28.2 mg/kg and in rabbits starting at 14.1 mg/kg; corresponding to exposures (based on AUC) that are approximately 2.5-times (mice) or 9.3-times (rabbits) the human exposure at the recommended clinical dose. 8.2. Lactation Risk Summary There is no data on the presence of imetelstat in human milk, or the effects RYTELO on the breastfed child, or milk production. Because of the potential for adverse reactions in breastfed children, advise women not to breastfeed during treatment with RYTELO and for 1 week after the last dose. 8.3. Females and Males of Reproductive Potential Based on findings from animal studies, RYTELO can cause embryo-fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1) ] . Pregnancy Testing Verify the pregnancy status of females of reproductive potential prior to initiating treatment with RYTELO. Contraception Females Advise females of reproductive potential to use effective contraception during treatment with RYTELO and for 1 week after the last dose [see Use in Specific Populations (8.1) ] . Infertility Females Based on findings in animals, RYTELO may impair fertility in females of reproductive potential. The effect on fertility is reversible [see Nonclinical Toxicology (13.1) ] . 8.4. Pediatric Use Safety and effectiveness of RYTELO in pediatric patients have not been established. 8.5. Geriatric Use Of the 118 patients with low- to intermediate-1 risk myelodysplastic syndromes (MDS) in the clinical trial who received RYTELO, 91 (77.1%) patients were 65 years of age and older and 35 (29.7%) patients 75 years of age and older. No differences in safety or efficacy were observed between older (≥ 65 years) and younger patients.

Pregnancy

8.1. Pregnancy Risk Summary Based on findings in animal studies, RYTELO can cause embryo-fetal harm when administered to a pregnant woman. There are no available data on RYTELO use in pregnant women to evaluate for drug-associated risk. In embryo-fetal developmental toxicity studies, administration of imetelstat to pregnant mice and rabbits during the period of organogenesis resulted in embryo-fetal mortality, which in mice occurred at maternal exposures approximately 2.5 times the human exposure at the recommended clinical dose. Advise pregnant women of the potential risk to a fetus [see Data ] . In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In embryo-fetal developmental toxicity studies, imetelstat was administered by IV bolus injection at doses of 4.7, 9.4, 14.1 or 28.2 mg/kg/day on gestation days 6, 9, and 12 in mice, or by 2-hour intravenous infusion at doses of 4.7, 14.1, or 28.2 mg/kg on gestation days 6 and 13 in rabbits. In rabbits, the dose of 28.2 mg/kg was maternally toxic. Increased post-implantation loss due to an increase in early resorptions, resulting in a decrease in viable fetuses and litter was noted in mice at 28.2 mg/kg and in rabbits starting at 14.1 mg/kg; corresponding to exposures (based on AUC) that are approximately 2.5-times (mice) or 9.3-times (rabbits) the human exposure at the recommended clinical dose.

Pediatric use

8.4. Pediatric Use Safety and effectiveness of RYTELO in pediatric patients have not been established.

Geriatric use

8.5. Geriatric Use Of the 118 patients with low- to intermediate-1 risk myelodysplastic syndromes (MDS) in the clinical trial who received RYTELO, 91 (77.1%) patients were 65 years of age and older and 35 (29.7%) patients 75 years of age and older. No differences in safety or efficacy were observed between older (≥ 65 years) and younger patients.

Description

11. DESCRIPTION RYTELO for injection contains imetelstat, an oligonucleotide telomerase inhibitor for intravenous use. Imetelstat sodium is a white to off-white or slightly yellow, amorphous, solid powder. It is highly soluble in aqueous solutions, including in 0.9% Sodium Chloride Injection, at both refrigerated and room temperatures. Imetelstat sodium is hygroscopic. The chemical name for the imetelstat sodium drug substance is DNA, d(3'-amino-3'-deoxy-P-thio) (T-A-G-G-G-T-T-A-G-A-C-A-A), 5'-[ O -[2-hydroxy-3-(hexadecanoylamino)propyl] phosphorothioate], sodium salt (1:13). The molecular formula is C 148 H 198 N 68 O 53 P 13 S 13 Na 13 (as sodium salt), which equates to a formula weight of 4896 g/mol. The molecular formula for the free acid form is C 148 H 211 N 68 O 53 P 13 S 13 which equates to a formula weight of 4610 g/mol. The structural formula for imetelstat sodium is: RYTELO (imetelstat) for injection is a sterile, preservative-free, white to off-white or slightly yellow lyophilized powder for intravenous infusion after reconstitution and dilution. Each single-dose vial provides either 47 mg of imetelstat (equivalent to 50 mg imetelstat sodium) or 188 mg of imetelstat (equivalent to 200 mg imetelstat sodium). The following inactive ingredients may be added during manufacturing: sodium carbonate anhydrous (for the 47 mg preparation) / sodium carbonate monohydrate (for the 188 mg preparation) or hydrochloric acid (to adjust to pH of 7.0 to 8.5). Chemical Structure

Mechanism of action

12.1. Mechanism of Action Imetelstat is an oligonucleotide human telomerase inhibitor that binds to the template region of the RNA component of human telomerase (hTR), inhibits telomerase enzymatic activity and prevents telomere binding. Increased telomerase activity and human telomerase reverse transcriptase (hTERT) RNA expression have been reported in MDS and malignant stem and progenitor cells. Nonclinical studies showed imetelstat treatment led to reduction of telomere length, reduction of malignant stem and progenitor cell proliferation, and induction of apoptotic cell death.

How supplied

16. HOW SUPPLIED/STORAGE AND HANDLING How Supplied RYTELO (imetelstat) for injection is a preservative free, white to off-white or slightly yellow, lyophilized powder available as: Carton Contents NDC One RYTELO 47 mg single-dose vial 82959-112-01 One RYTELO 188 mg single-dose vial 82959-111-01 Storage Store vials refrigerated at 2°C to 8°C (36°F to 46°F) in original carton. Do not freeze.

Storage

Storage Store vials refrigerated at 2°C to 8°C (36°F to 46°F) in original carton. Do not freeze.

Patient information

17. PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Discuss the following with patients prior to and during treatment with RYTELO. Thrombocytopenia Advise patients of the risk of thrombocytopenia with RYTELO, and that their blood counts will be monitored routinely while on treatment and dose of RYTELO delayed or reduced as needed. Instruct patients to notify a healthcare provider immediately if they show signs or symptoms of thrombocytopenia such as unusual bleeding or bruising [see Warnings and Precautions (5.1) ] . Neutropenia Advise patients of the risk of neutropenia with RYTELO and that their blood counts will be monitored routinely while on treatment and the dose of RYTELO may be delayed or reduced as needed. Instruct patients to notify a healthcare provider immediately if they show signs or symptoms of neutropenia, such as fever or infection [see Warnings and Precautions (5.2) ] . Infusion-Related Reactions Inform patients that infusion-related reactions can occur during treatment with RYTELO and premedications will be given prior to each infusion. Patients will be monitored by their healthcare provider for at least an hour after the infusion [see Dosage and Administration (2.2) and Warnings and Precautions (5.3) ] . Advise patients that their healthcare provider may decide to give RYTELO more slowly or stop the infusion if an infusion-related reaction occurs [see Adverse Reactions (6.1) ] Embryo-Fetal Toxicity Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to inform their healthcare provider if they are pregnant or become pregnant [see Warnings and Precautions (5.4) and Use in Specific Populations (8.1) ] . Advise females of reproductive potential to use effective contraception during treatment with RYTELO and for 1 week after the last dose [see Use in Specific Populations (8.3) ] . Lactation Advise women not to breastfeed during treatment with RYTELO and for 1 week after the last dose [see Use in Specific Populations (8.2) ] .

Label text from the FDA structured product label by Geron Corporation (revised Apr 22, 2026). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Rytelo NDC products (2)

NDCStrength & formLabelerType
82959-111Imetelstat Sodium 188 mg/1
Injection, Powder, Lyophilized, For Solution		Geron CorporationNDA
82959-112Imetelstat Sodium 47 mg/1
Injection, Powder, Lyophilized, For Solution		Geron CorporationNDA

Frequently asked questions

What is Rytelo used for?

1. INDICATIONS AND USAGE RYTELO is indicated for the treatment of adult patients with low- to intermediate-1 risk myelodysplastic syndromes (MDS) with transfusion-dependent anemia requiring 4 or more red blood cell units over 8 weeks who have not responded to or have lost response to or are ineligible for erythropoiesis-stimulating agents (ESA). RYTELO is an oligonucleotide telomerase inhibitor…

What are the side effects of Rytelo?

6. ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Thrombocytopenia [see Warnings and Precautions (5.1) ] Neutropenia [see Warnings and Precautions (5.2) ] Infusion-Related Reactions [see Warnings and Precautions (5.3) ] Most common adverse reactions (incidence ≥10% with a difference between arms of >5% compared to placebo),… See the full label for the complete list.

Who makes Rytelo?

Rytelo is listed by 1 labeler in the FDA NDC directory, including Geron Corporation.