New FDA Approval: RYTELO™ (imetelstat)
1 minute
On June 6, 2024, the Food and Drug Administration approved imetelstat (Rytelo, Geron Corporation), an oligonucleotide telomerase inhibitor, for adults with low- to intermediate-1 risk myelodysplastic syndromes (MDS) with transfusion-dependent anemia requiring four 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 (ESAs).
Read InpharmD's summary below:
| Drug Name |
RYTELO™ (imetelstat) |
| Active Ingredient |
imetelstat |
| Date of Approval |
06/06/24 |
| Manufacturer |
Geron Corporation |
| Approval Pathways and Indications |
Approval Pathway: NDA
Indication: 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). |
| Therapeutic Class |
First-in-Class Telomerase Inhibitor |
| Formulation |
Injection, for Intravenous Use |
| MoA |
Imetelstat is an oligonucleotide human telomerase inhibitor that binds to the template region of the ribonucleic acid (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. |
| Dosing 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.
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 |
| Administered by self or by HCP |
Administered by HCP |
| Place in Therapy |
Lower-risk MDS is a progressive blood cancer with high unmet need, where many patients with anemia become dependent on red blood cell transfusions, which can be associated with clinical consequences and decreased quality of life.
RYTELO™ is a first-in-class treatment that works by inhibiting telomerase enzymatic activity. Telomeres are protective caps at the end of chromosomes that naturally shorten each time a cell divides. In low-risk myelodysplastic syndromes (LR-MDS), abnormal bone marrow cells often express the enzyme telomerase, which rebuilds those telomeres, allowing for uncontrolled cell division. Developed and exclusively owned by Geron, RYTELO™ is the first and only telomerase inhibitor approved by the U.S. Food and Drug Administration (FDA).
"For patients with lower-risk MDS and anemia who are transfusion dependent, we have very few options today and often cycle through available therapies, making the approval of RYTELO™ potentially practice changing for us,” Rami Komrokji, M.D., vice chair, Malignant Hematology Department, Moffitt Cancer Center and investigator in the IMerge clinical trial, said in a press release. “The treatment goal for patients with LR-MDS and anemia is transfusion-independence and before today, this wasn’t possible for many patients.” |
| Expected Market Launch Date |
Summer 2024 |
| New Molecular Entity (NME) or Existing Formulation |
NME |
| Expected Cost |
For a 188 mg and 47 mg vial, the wholesale price of RYTELO™ is $9,884 and $2,471, respectively. |
| Product Discontinuation |
N/A |
| Clinical Trials |
The FDA approval of RYTELO™ is based on results from the IMerge Phase III clinical trial, published in The Lancet. 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% [95% CI 30.9–49.3]; placebo 15.0% [7.1–26.6]; p<0.001) and for at least 24 weeks (RYTELO 28.0% [95% CI 20.1-37.0]; placebo 3.3% [95% CI 0.4-11.5]; p<0.001). 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 the IMerge trial, the safety profile of RYTELO™ was well-characterized with generally manageable and short-lived thrombocytopenia and neutropenia, which are familiar side effects for hematologists who are experienced with managing cytopenias. The most common Grade 3/4 adverse reactions were neutropenia (72%) and thrombocytopenia (65%), which lasted a median duration of less than two weeks, and in more than 80% of patients were resolved to Grade < 2 in under four weeks. Cytopenias were generally manageable with dose modifications. |
| Sources |
https://www.biospace.com/article/releases/geron-announces-fda-approval-
of-rytelo-imetelstat-a-first-in-class-telomerase-inhibitor-for-the-treatment-
of-adult-patients-with-lower-risk-mds-with-transfusion-dependent-anemia/#:~:text=RYTELO%E2%84%A2%20(imetelstat)%
20is%20an,responded%20to%20or%20have%20lost
https://www.managedhealthcareexecutive.com/view/rytelo-gains-fda-approval-to-treat-low-risk-myelodysplastic-syndromes
https://pi.geron.com/products/US/pi/rytelo_pi.pdf |
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