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.

Who participated in the trial? 

Table 1. Demographics, Efficacy Population

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

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

_{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 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

<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 (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

_{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

_{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 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

<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>