Imetelstat

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).

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.

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. Premedicate prior to dosing with RYTELO for potential infusion-related reactions. See full prescribing information for preparation and administration instructions. 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. 2.2.

4. CONTRAINDICATIONS None. None.

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. 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. Infusion-Related Reactions: Premedicate before infusion. Interrupt, decrease the rate of infusion, or permanently discontinue RYTELO based on severity. Embryo-Fetal Toxicity: Can cause embryo-fetal harm. Advise females of reproductive potential of potential risk to a fetus and to use effective contraception. 5.1. Thrombocytopenia RYTELO can cause thrombocytopenia based on laboratory values.

6. ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Thrombocytopenia Neutropenia Infusion-Related Reactions 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. 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.

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