Drug Trials Snapshots: RYTELO

HOW TO USE THIS SNAPSHOT

The information provided in Snapshots highlights who participated in the key clinical trials that supported the original FDA approval of this drug, and whether there were differences among sex, race, age, and ethnic groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.

LIMITATIONS OF THIS SNAPSHOT

Do not rely on Snapshots to make decisions regarding medical care. Always speak to your healthcare provider about the benefits and risks of a drug. 

Some of the information in this Snapshot is for presentation purposes and does not represent the approved conditions of use of this drug. Refer to the RYTELO Prescribing Information for all of the approved conditions of use of this drug (e.g., indication(s), population(s), dosing regimen(s), safety information).

Snapshots are limited to the information available at the time of the original approval of the drug and do not provide information on who participated in clinical trials that supported later approvals for additional uses of the drug (if applicable).

RYTELO (imetelstat)
rye-TELL-oh
Geron Corporation
Original Approval date: June 6, 2024

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DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

RYTELO is a prescription medicine used to treat a condition called low- to intermediate-1 risk myelodysplastic syndromes (MDS) in adults with anemia (low red blood cell counts) who need four or more red blood cell (RBC) units over eight weeks and who have not responded to, have stopped responding to, or cannot be treated with other medications called erythropoiesis stimulating agents (ESAs).

How is this drug used?

RYTELO is given by a healthcare provider as an infusion into a vein over a period of two hours. RYTELO is usually given every four weeks.
Once RYTELO is given, the healthcare provider may change the dose or dosing schedule based on how the patient responds. Certain blood tests will be performed by the healthcare provider during treatment to check for side effects and to see how well a patient responds to treatment. The healthcare provider will decide how many treatment cycles of RYTELO will be given.

Who participated in the clinical trials?

The FDA approved RYTELO based on evidence from one clinical trial (IMerge) of 178 patients with low- or intermediate-1 risk MDS who were transfusion-dependent (requiring ≥4 RBC units over an 8 week period during the 16 weeks prior to being enrolled in the trial) and had failed to respond to, had lost response to, or were not eligible to receive an ESA. The trial was conducted at 77 sites in 17 countries in North America, Europe, and the rest of the world.

How were the trials designed? 

RYTELO was evaluated in one clinical trial of patients with lower risk MDS with transfusion-dependent anemia. Patients were randomly assigned 2:1 to receive RYTELO 7.1 mg/kg (N=118) or placebo (N=60) by infusion every 28 days until their disease worsened or until the healthcare provider determined the participant could not tolerate the medicine.
 

How were the trials designed? 

The efficacy and safety of RYTELO were evaluated in patients with low- to intermediate-1 risk MDS who were transfusion-dependent (requiring ≥4 RBC units over an 8 week period during the 16 weeks prior to being enrolled in the trial) in a placebo-controlled, multi-center study (IMerge). Neither the healthcare provider nor the patient was told at the time whether the patient was assigned to receive RYTELO or placebo. The study included patients who had failed to respond to, had lost response to, or were not eligible to receive an ESA.

The benefit of RYTELO was evaluated by measuring the proportion of patients who experienced a period of eight weeks or longer without needing an RBC transfusion. The benefit was also evaluated as a secondary assessment of efficacy by measuring the proportion of patients who experienced a period of 24 weeks or longer without needing an RBC transfusion.

Patients in the RYTELO group received RYTELO 7.1 mg/kg every four weeks by intravenous infusion over two hours. Patients also received pretreatment medications and could receive supportive care, if needed.

DEMOGRAPHICS SNAPSHOT

Figure 1 summarizes the percentage of males and females in the clinical trial used to evaluate the efficacy of RYTELO.

Figure 1. Baseline Demographics by Sex, Efficacy Population

_{Source: Adapted from FDA Review}

Figure 2 summarizes how many subjects by race were enrolled in the clinical trial used to evaluate the efficacy of RYTELO.

Figure 2. Baseline Demographics by Race, Efficacy Population

<sub>Source: Adapted from FDA Review
* Other includes unknown and not reported race participants</sub>

Figure 3 summarizes how many subjects by age were enrolled in the clinical trial used to evaluate the efficacy of RYTELO.

Figure 3. Baseline Demographics by Age, Efficacy Population

_{Source: Adapted from FDA Review}

Figure 4 summarizes how many subjects by ethnicity were enrolled in the clinical trial used to evaluate the efficacy of RYTELO.

Figure 4. Baseline Demographics by Ethnicity, Efficacy Population

<sub>Source: Adapted from FDA Review
* Unknown includes not reported ethnicity participants</sub>

Who participated in the trial? 

Table 1. Demographics, Efficacy Population

Demographic	RYTELO N=118	Placebo N=60	Total N=178
Sex, n (%)
Male	71 (60.2)	40 (66.7)	111 (62.4)
Female	47 (39.8)	20 (33.3)	67 (37.6)
Race, n (%)
White	95 (80.5)	48 (80.0)	143 (80.3)
Asian	8 (6.8)	2 (3.3)	10 (5.6)
Black or African American	1 (0.8)	2 (3.3)	3 (1.7)
Other	1 (0.8)	1 (1.7)	2 (1.1)
Unknown	1 (0.8)	1 (1.7)	2 (1.1)
Not reported*	12 (10.2)	6 (10.0)	18 (10.1)
Age, years
Median	71.5	73.0	72.0
Minimum, maximum	44, 87	39, 85	39, 87
Age category, years, n (%)
<65	27 (22.9)	9 (15.0)	36 (20.2)
≥65	91 (77.1)	51 (85.0)	142 (79.8)
Ethnicity, n (%)
Hispanic or Latino	6 (5.1)	5 (8.3)	11 (6.2)
Not Hispanic or Latino	100 (84.7)	48 (80.0)	148 (83.1)
Unknown	1 (0.8)	1 (1.7)	2 (1.1)
Not reported*	11 (9.3)	6 (10.0)	17 (9.6)

<sub>Source: Adapted from FDA Review 
* Race or ethnicity data collection prohibited due to regional restrictions</sub>

What are the benefits of this drug? 

In a clinical trial of 178 patients with transfusion dependent lower-risk MDS, 47 out of 118 (40%) patients treated with RYTELO and 9 out of 60 (15%) of patients on placebo achieved at least eight weeks of transfusion independence.

What are the benefits of this drug (results of trials used to assess efficacy)? 

Efficacy was established based on the number of patients in the RYTELO and placebo groups who achieved ≥8-week and ≥24-week red blood cell-transfusion independence (RBC-TI), defined as the absence of RBC transfusion(s) during any consecutive 8-weeks (56 days) period, and during any consecutive 24-weeks (168 days) period, respectively, from randomization until the start of subsequent anti-cancer therapy (if any).

The efficacy results are summarized in Table 2.

Table 2. Efficacy Results, Efficacy Population

Parameter	RYTELO, N=118		Placebo, N=60		Difference
	n(%)	95% CI	n(%)	95% CI	% (95% CI)	p-value
≥8-week RBC-TI	47 (39.8)	30.9, 49.3	9 (15.0)	7.1, 26.6	24.8 (9.9, 36.9)	<0.001
≥24-week RBC-TI	33 (28.0)	20.1, 37.0	2 (3.3)	0.4, 11.5	24.6 (12.6, 34.2)	<0.001

_{Source: Adapted from RYTELO Prescribing Information
Abbreviations: CI, confidence Interval; RBC-TI, red blood cell-transfusion independence}

Were there any differences in how well the drug worked in clinical trials among sex, race, and age? 

• Sex: RYTELO worked similarly in males and females.
• Race: Most patients who received RYTELO in this study were White, and the numbers in other race groups were too small to assess whether RYTELO worked better or worse in those groups.
• Age: RYTELO worked similarly across age groups studied.

Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups? 

Table 3 summarizes the subgroup analysis for patients who achieved ≥8-week RBC-TI. Differences in how well the drug worked in racial and ethnic subgroups are challenging to interpret due to the small number of participants in each subgroup.

Table 3. Patients Who Achieved ≥8-Week RBC-TI by Subgroup, Efficacy Population

Subgroup	RYTELO, N=118		Placebo, N=60		Difference
	n/Ns(%)	95% CI	n/Ns(%)	95% CI	% (95% CI)
Sex
Female	17/47 (36.2)	22.7, 51.5	1/20 (5.0)	0.1, 24.9	31.2 (5.6, 47.2)
Male	30/71 (42.3)	30.6, 54.6	8/40 (20.0)	0.1, 35.6	22.3 (2.5, 38.3)
Age, years
<65	10/27 (37.0)	19.4, 57.6	1/9 (11.1)	0.3, 48.2	25.9 (-15.9, 49.0)
≥65	37/91 (40.7)	30.5, 51.5	8/51 (15.7)	7.0, 28.6	25.0 (8.2, 38.5)
Race
White	36/95 (37.9)	28.1, 48.4	6/48 (12.5)	4.7, 25.2	25.4 (8.9, 38.5)
Asian	4/8 (50.0)	15.7, 84.3	2/2 (100.0)	15.8, 100.0	-50.0 (-82.6, 36.6)
Black or African American	0/1 (0.0)	0.0, 97.5	0/2 (0.0)	0.0, 84.2	0.0 (-80.2, 94.5)
Other*	7/14 (50.0)	23.0, 77.0	1/8 (12.5)	0.3, 52.7	37.5 (-10.9, 66.0)
Ethnicity
Hispanic or Latino	1/6 (16.7)	0.4, 64.1	1/5 (20.0)	0.5, 71.6	-3.3 (-55.9, 47.2)
Not Hispanic or Latino	40/100 (40.0)	30.3, 50.3	7/48 (14.6)	6.1, 27.8	25.4 (8.7, 38.5)
Not reported or unknown	6/12 (50.0)	21.1, 78.9	1/7 (14.3)	0.4, 57.9	35.7 (-16.0, 66.6)

<sub>Source: Adapted from FDA Review 
* Other includes unknown and not reported race participants
Abbreviations: CI, confidence interval; N, number of patients in treatment arm; n, number of patients meeting criteria; Ns, total number of patients for each specific subgroup and were assigned to that specific arm; RBC-TI, red blood cell-transfusion independence</sub>

What are the possible side effects?

RYTELO may cause serious side effects including low platelet counts (thrombocytopenia), which can increase the risk for bleeding; and low neutrophil counts (neutropenia), which can increase the risk for infections including serious infections and sepsis. Both side effects are very common and can also be severe. RYTELO may also cause infusion-related reactions during or after the infusion is given, which can be severe including a severe sudden increase in blood pressure called hypertensive crisis.

The most common side effects of RYTELO are decreased platelet counts; decreased white blood cell counts; decreased neutrophil counts; increased liver enzymes (aspartate aminotransferase, alkaline phosphatase, and alanine aminotransferase); tiredness; longer than usual blood clotting times; joint, bone, and muscle pain; COVID-19 infections; and headache.

RYTELO may cause harm to an unborn baby (embryo-fetal toxicity) and may cause loss of pregnancy (miscarriage). RYTELO may cause fertility problems in females who are pregnant or plan to become pregnant.

What are the possible side effects (results of trials used to assess safety)? 

Table 4 summarizes adverse reactions in the clinical trial.

Table 4. Adverse Reactions (≥5%) in Patients With MDS Who Received RYTELO With a Difference Between Arms of >2% Compared to Placebo in IMerge, Safety Population

Body System Adverse Reaction	RYTELO, N=118		Placebo, N=59
	All Grades %	Grades 3 or 4 %	All Grades %	Grades 3 or 4 %
General disorders and administrative site conditions
Fatiguea	29	0	20	3.4
Musculoskeletal and connective tissue disorders
Arthralgia or myalgiab	25	2.5	19	5
Infections and infestations
COVID-19c	19	1.7	14	5
Urinary tract infectiond	9	2.5	7	0
Nervous system disorders
Headache	13	0.8	5	0
Syncopee	7	1.7	1.7	0
Immune system disorders
Infusion-related reactionsf	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 arrhythmiag	6	1.7	3.4	1.7
Injury, poisoning and procedural complications
Fracturesh	5	3.4	1.7	1.7

_{Source: RYTELO Prescribing Information
Graded according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03.
a  Fatigue: asthenia, fatigue, and malaise.
b Arthralgia or 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.
c COVID-19: asymptomatic COVID-19, COVID-19, COVID-19 pneumonia, and SARS-CoV-2 antibody test positive.
d Urinary tract infection: cystitis, Escherichia urinary tract infection, renal abscess, and urinary tract infection.
e Syncope: fall, pre-syncope, and syncope.
f 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. 
g Atrial arrhythmia: atrial fibrillation and atrial flutter.
h Fractures: femur fracture, hand fracture, hip fracture, humerus fracture, lumbar vertebral fracture, and thoracic vertebral fracture.
Abbreviations: MDS, myelodysplastic syndromes; SARS, severe acute respiratory syndrome}

Clinically relevant adverse reactions that occurred in less than 5% of patients who received RYTELO included febrile neutropenia, sepsis, gastrointestinal hemorrhage, and hypertension.

Table 5 summarizes laboratory abnormalities in the clinical trial.

Table 5. Select Laboratory Abnormalities (≥10%) That Worsened From Baseline in Patients With MDS Who Received RYTELO With a Difference Between Arms of >2% Compared to Placebo in IMerge, Safety Population

Laboratory Abnormality	RYTELO1		Placebo2
	All Grades %	Grade 3 or 4 %	All Grades %	Grade 3 or 4 %
Hematology
Platelet count decreased	97	65	34	8
White blood cell count decreased	94	53	59	1.7
Neutrophil count decreased	92	72	47	7
PTT prolonged	26	1	18	4
Chemistry
AST increased	53	0.8	22	1.7
ALP increased	48	0	12	0
ALT increased	43	3.4	37	5

_{Source: RYTELO Prescribing Information
Graded according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03.
1 The denominator used to calculate the rate varied from 97 to 118 based on the number of patients with a baseline value and at least one post-treatment value.
2 The denominator used to calculate the rate varied from 50 to 59 based on the number of patients with a baseline value and at least one post-treatment value.
Abbreviations: ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; MDS, myelodysplastic syndromes; PTT, partial thromboplastin time}

Were there any differences in side effects among sex, race, and age?

• Sex: There were no notable differences in the occurrence of side effects by sex.
• Race: There were no notable differences in the occurrence of side effects by race.
• Age: There were no differences in the occurrence of side effects by age.

Were there any differences in side effects of the clinical trials among sex, race, and age groups? 

Table 6 summarizes adverse events by subgroups in the 118 patients who received RYTELO in the Phase 3 trial.

Table 6. Adverse Events by Subgroup, Safety Population

Subgroup	RYTELO, N=118
	All Grades n/Ns (%)	Grades 3 or 4 n/Ns (%)
Sex
Female	46/47 (97.9)	42/47 (89.4)
Male	71/71 (100.0)	66/71 (93.0)

<sub>Source: Adapted from FDA Review
* Other includes unknown and not reported race participants
Abbreviations: N, number of patients in treatment arm; n, number of patients with adverse event; Ns, total number of patients for each specific subgroup and were assigned to that specific arm</sub>

GLOSSARY

CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.

COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.

EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.

PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.

SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.

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