Profile
General Information
Rytelo (imetelstat) is an oligonucleotide telomerase inhibitor.
Rytelo is specifically 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).
Dosing/Administration
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
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
Mechanism of Action
Rytelo (imetelstat) is an oligonucleotide 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 13 treatment led to reduction of telomere length, reduction of malignant stem and progenitor cell proliferation, and induction of apoptotic cell death.
Side Effects
Adverse effects associated with the use of Rytelo may include, but are not limited to, the following:
- 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
- headache
Clinical Trial Results
The FDA approval of Rytelo was based on results from the IMerge Phase 3 clinical trial. The IMerge trial met its primary and key secondary endpoints, with Rytelo demonstrating significantly higher rates of red blood cell transfusion independence (RBC-TI) versus placebo for at least eight consecutive weeks (Rytelo 39.8%; placebo 15.0%) and for at least 24 weeks (Rytelo 28.0% placebo 3.3%). RBC-TI was durable and sustained in the Rytelo treated population, with a median RBC-TI duration for 8-week responders and 24-week responders of approximately 1 year and 1.5 years, respectively.
In an exploratory analysis of Rytel-treated patients achieving ≥8-week RBC-TI, median increases in hemoglobin were 3.6 g/dL for Rytelo and 0.8 g/dL for placebo. Clinically meaningful efficacy results were observed across key MDS subgroups irrespective of ring sideroblast (RS) status, baseline transfusion burden and IPSS risk category.