SAFETY
Safety Profile
The safety evaluation of Reblozyl in MDS is based on the double-blind, randomized, placebo-controlled, phase 3 MEDALIST trial (with 153 patients treated with Reblozyl and 76 patients receiving placebo).1
The most commonly reported Grade 3 or higher adverse drug reactions (at least 2% of patients) included syncope/presyncope, fatigue, hypertension, and asthenia. The most commonly reported serious adverse drug reactions (at least 2% of patients) were urinary tract infection, back pain, and syncope.1
Most frequently reported adverse drug reactions
in at least 15% of patients receiving Reblozyl1
Fatigue
Diarrhea
Asthenia
Nausea
Dizziness
Back pain
Headache
Asthenia, fatigue, dizziness, and headache occurred more frequently during the first 3 months of treatment1
The frequency for each adverse reaction observed in the MEDALIST trial is shown in the center table.
| ADVERSE DRUG REACTIONS IN PATIENTS TREATED WITH REBLOZYL FOR MDS1 |
||
|---|---|---|
| SYSTEM ORGAN CLASS | PREFERRED TERM | FREQUENCY (ALL GRADES)a |
| Infections and infestations | Bronchitis | Very common |
| Urinary tract infection | Very common | |
| Upper respiratory tract infection |
Common | |
| Influenza | Common | |
| Immune system disorders | Hypersensitivityb | Common |
| Metabolism and nutrition disorders |
Hyperuricemia | Common |
| Nervous system disorders | Dizziness | Very common |
| Headache | Very common | |
| Syncope/presyncope | Common | |
| Ear and labyrinth disorders | Vertigo/vertigo positional | Common |
| Vascular disorders | Hypertensionc | Common |
| Thromboembolic eventsd | Common | |
| Respiratory, thoracic and mediastinal disorders |
Dyspnea | Very common |
| Gastrointestinal disorders | Diarrhea | Very common |
| Nausea | Very common | |
| Musculoskeletal and connective tissue disorders |
Back pain | Very common |
| Arthralgia | Common | |
| Bone pain | Common | |
| General disorders and administration site conditions |
Fatigue | Very common |
| Asthenia | Very common | |
| Injection site reactionse | Common | |
aFrequencies are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), and very rare (<1/10,000).
bHypersensitivity includes eyelid edema, drug hypersensitivity, swelling face, periorbital edema, face edema, angioedema, lip swelling, and drug eruption.
cHypertension reaction includes essential hypertension, hypertension, and hypertensive crisis.
dThromboembolic events include deep vein thrombosis, portal vein thrombosis, ischemic stroke, and pulmonary embolism.
eInjection site reactions include injection site erythema, injection site pruritus, injection site swelling, and injection site rash.
Safety Profile
The safety evaluation of Reblozyl in MDS is based on the double-blind, randomized, placebo-controlled, Phase 3 MEDALIST trial (with 153 patients treated with Reblozyl and 76 patients receiving placebo).1
Fatigue
Dizziness
Diarrhea
Back pain
Asthenia
Headache
Nausea
Asthenia, fatigue, dizziness, and headache occurred less frequently after the first 3 months of treatment1
The most commonly reported Grade 3 or higher adverse drug reactions (at least 2% of patients)included syncope/presyncope, fatigue, hypertension, and asthenia. The most commonly reported serious adverse drug reactions (at least 2% of patients) were urinary tract infection, back pain, and syncope.1
Adverse drug reactions observed
| ADVERSE DRUG REACTIONSOBSERVED AND REPORTED IN PATIENTS TREATED WITH REBLOZYL FOR MDS1 | |
|---|---|
| SYSTEM ORGAN CLASS PREFERRED TERM |
FREQUENCY (ALL GRADES)a |
| Infections and infestations | |
| Bronchitis | Very common |
| Urinary tract infection | Very common |
| Upper respiratory tract infection | Common |
| Influenza | Common |
| Immune system disorders | |
| Hypersensitivityb | Common |
| Metabolism and nutrition disorders | |
| Hyperuricemia | Common |
| Nervous system disorders | |
| Dizziness | Very common |
| Headache | Very common |
| Syncope/presyncope | Common |
| Ear and labyrinth disorders | |
| Vertigo/vertigo positional | Common |
| Vascular disorders | |
| Hypertensionc | Common |
| Thromboembolic eventsd | Common |
| Respiratory, thoracic and mediastinal disorders | |
| Dyspnea | Very common |
| Gastrointestinal disorders | |
| Diarrhea | Very common |
| Nausea | Very common |
| Musculoskeletal and connective tissue disorders | |
| Back pain | Very common |
| Arthralgia | Common |
| Bone pain | Common |
| General disorders and administration site conditions | |
| Fatigue | Very common |
| Asthenia | Very common |
| Injection site reactionse | Common |
a Frequencies are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), and very rare (<1/10,000). [Reblozyl Draft SPC/p7/para4/lns3-5]
b Hypersensitivity includes eyelid edema, drug hypersensitivity, swelling face, periorbital edema, face edema, angioedema, lip swelling, and drug eruption.
c Hypertension reaction includes essential hypertension, hypertension, and hypertensive crisis.
d Thromboembolic events include deep vein thrombosis, portal vein thrombosis, ischemic stroke, and pulmonary embolism.
e Injection site reactions include injection site erythema, injection site pruritus, injection site swelling, and injection site rash.
Selected adverse reactions
Selected adverse reactions across MEDALIST and BELIEVE trials1
- Hypersensitivity: Hypersensitivity-type reactions (including eyelid edema, drug hypersensitivity, swelling face, periorbital edema, face edema, angioedema, lip swelling, drug eruption) were reported in 4.6% of patients with MDS (2.6% placebo) and 4.5% of patients with β-thalassemia treated with Reblozyl (1.8% placebo). In clinical studies, all events were Grade 1/2. In patients with β-thalassemia treated with Reblozyl, hypersensitivity led to treatment discontinuation in 1 patient (0.4%).
- Injection site reactions: Injection site reactions (including injection site erythema, injection site pruritus, injection site swelling, and injection site rash) were reported in 3.9% of patients with MDS (placebo 0.0%) and in 2.2% of patients with β-thalassemia receiving Reblozyl (placebo 1.8%). In clinical studies, all events were Grade 1 and none led to discontinuation.
- Immunogenicity: In an analysis of 260 patients with MDS who were treated with Reblozyl and who were evaluable for the presence of anti-luspatercept antibodies, 8.8% of MDS patients tested positive for treatment‑emergent anti-luspatercept antibodies, including 3.5% of MDS patients who had neutralizing antibodies against Reblozyl
In an analysis of 284 patients with β-thalassemia who were treated with Reblozyl and who were evaluable for the presence of anti-luspatercept antibodies, 4 (1.4%) patients tested positive for treatment-emergent anti-luspatercept antibodies, including 2 (0.7%) patients who had neutralizing antibodies against Reblozyl
- There were no severe systemic hypersensitivity reactions reported for patients with anti-luspatercept antibodies
- There was no association between hypersensitivity type reactions or injection site reactions and presence of anti-luspatercept antibodies
- Thromboembolic events (TEEs): Thromboembolic events (including deep vein thrombosis, portal vein thrombosis, ischemic stroke and pulmonary embolism) occurred in 3.6% of patients with β-thalassemia receiving Reblozyl (placebo 0.9%). All events were reported in patients who had undergone splenectomy and had at least 1 other risk factor. No difference in TEEs was observed between Reblozyl and placebo arms in patients with MDS
- Hypertension: Patients treated with Reblozyl had an average increase in systolic and diastolic blood pressure of 5 mm Hg from baseline not observed in patients receiving placebo. Hypertension was reported in 8.5% of patients with MDS (placebo 9.2%) and in 8.1% of patients with β-thalassemia (placebo 2.8%).
- In patients with MDS, Grade 3 events were reported for 5 patients (3.3%) treated with Reblozyl and in 3 patients (3.9%) receiving placebo. No patient discontinued due to hypertension.
- In patients with β-thalassemia, Grade 3 events were reported in 4 patients (1.8%) treated with Reblozyl (0.0% placebo). No patient discontinued due to hypertension
- Arthralgia: Arthralgia was reported in 19.3% of patients with β-thalassemia treated with Reblozyl (placebo 11.9%) and in 5.2% of patients with MDS treated with Reblozyl (placebo 11.8%). In the patients with β-thalassemia treated with Reblozyl, arthralgia led to treatment discontinuation in 2 patients (0.9%).
- Bone pain: Bone pain was reported in 19.7% of patients with β-thalassemia treated with Reblozyl (placebo 8.3%) and in 2.6% of patients with MDS treated with Reblozyl (placebo 3.9%). In patients with β-thalassemia treated with Reblozyl, bone pain was most common in the first 3 months (16.6%) compared with months 4-6 (3.7%). Most events (41/44 events) were Grade 1-2, with 3 events Grade 3. One of the 44 events was serious, and 1 event led to treatment discontinuation.
Selected adverse reactions in patients with MDS1
Higher instance of adverse reactions with Reblozyl vs placebo in the MEDALIST trial
Hypersensitivity
4.6% Reblozyl
2.6% Placebo
All events were Grade 1 or 2
Injection site reactions
3.9% Reblozyl
0% Placebo
All were Grade 1 and did not lead to treatment discontinuation
Other adverse reactions in MDS
Immunogenicity
8.8% of Reblozyl patients tested positive for
treatment-emergent anti-luspatercept antibodies
Thromboembolic events
No difference between Reblozyl and Placebo
Hypertension
8.5% Reblozyl
9.2% Placebo
Grade 3 events were reported in 5 patients receiving Reblozyl (3.3%);
none led to treatment discontinuation
Arthralgia
5.2% Reblozyl
11.8% Placebo
Bone pain
2.6% Reblozyl
3.9% Placebo
Selected adverse reactions
Selected adverse reactions in patients with MDS1
Higher instance of adverse reactions with Reblozyl vs placebo in the MEDALIST trial1
Hypersensitivity
4.6% Reblozyl
2.6% Placebo
Hypersensitivity-type reactions (including eyelid edema, drug hypersensitivity, swelling face, periorbital edema, face edema, angioedema, lip swelling, drug eruption) were reported in 4.6% of patients with MDS (2.6% placebo) and 4.5% of patients with β-thalassemia treated with Reblozyl (1.8% placebo).In clinical studies, all events were Grade 1/2. In patients with β-thalassemia treated with Reblozyl, hypersensitivity led to treatment discontinuation in 1 patient (0.4%).1
Injection site reactions
3.9% Reblozyl
0% Placebo
Injection site reactions (including injection site erythema, injection site pruritus, injection site swelling and injection site rash) were reported in 3.9% of patients with MDS (placebo 0.0%) and in 2.2% of patients with β-thalassemia receiving Reblozyl (placebo 1.8%). In clinical studies, all events were Grade 1 and none led to discontinuation.1
Other adverse reactions in MDS
Immunogenicity
8.8% of Reblozyl patients tested positive for treatment-emergent anti-Reblozyl antibodies
In an analysis of 260 patients with MDS who were treated with Reblozyl and who were evaluable for the presence of anti-Reblozyl antibodies, 8.8% of patients tested positive for treatment‑emergent anti-Reblozyl antibodies, including 3.5% of patients who had neutralizing antibodies against Reblozyl1
In an analysis of 284 patients with ß-thalassemia who were treated with Reblozyl and who were evaluable for the presence of anti-luspatercept antibodies, 4 (1.4%) patients tested positive for treatment-emergent anti-luspatercept antibodies, including 2 (0.7%) patients who had neutralizing antibodies against Reblozyl1
- There were no severe systemic hypersensitivity reactions reported for patients with anti-luspatercept antibodies1
- There was no association between hypersensitivity type reactions or injection site reactions and presence of anti-luspatercept antibodies1
Thromboembolic Events
No difference between Reblozyl and placebo
Thromboembolic events (including deep vein thrombosis, portal vein thrombosis, ischemic stroke and pulmonary embolism) occurred in 3.6% of patients with β-thalassemia receiving Reblozyl (placebo 0.9%). All events were reported in patients who had undergone splenectomy and had at least 1 other risk factor. No difference in TEEs was observed between Reblozyl and placebo arms in MDS patients1
Hypertension
8.5% Reblozyl
9.2% Placebo
Patients treated with Reblozyl had an average increase in systolic and diastolic blood pressure of 5 mm Hg from baseline not observed in patients receiving placebo. Hypertension was reported in 8.5% of patients with MDS (placebo 9.2%) and in 8.1% of patients with ß-thalassemia (placebo 2.8%).1
- In patients with MDS, Grade 3 events were reported for 5 patients (3.3%) treated with Reblozyl and in 3 patients (3.9%) receiving placebo. No patient discontinued due to hypertension.1
- In patients with β-thalassemia, Grade 3 events were reported in 4 patients (1.8%) treated with Reblozyl (0.0% placebo). No patient discontinued due to hypertension1
Arthralgia
5.2% Reblozyl
11.8% Placebo
Arthralgia was reported in 19.3% of patients with ß-thalassemia treated with Reblozyl (placebo 11.9%) and in 5.2% of patients with MDS treated with Reblozyl (placebo 11.8%). In the patients with β-thalassemia treated with Reblozyl, arthralgia led to treatment discontinuation in 2 patients (0.9%).1
Bone Pain
2.6% Reblozyl
3.9% Placebo
Bone pain was reported in 19.7% of patients with β-thalassemia treated with Reblozyl (placebo 8.3%) and in 2.6% of patients with MDS treated with Reblozyl (placebo 3.9%). In patients with β-thalassemia treated with Reblozyl, bone pain was most common in the first 3 months (16.6%) compared with months 4-6 (3.7%). Most events (41/44 events) were Grade 1-2, with 3 events Grade 3. One of the 44 events was serious, and 1 event led to treatment discontinuation.1
Discontinuations
Treatment discontinuation due to an adverse reaction occurred in 2.0% of patients with MDS. The adverse reactions leading to treatment discontinuation in the Reblozyl arm were fatigue and headache.1
Discontinuations
of MDS patients receiving Reblozyl discontinued treatment due to an adverse reaction1
The adverse reactions leading to treatment discontinuation in the Reblozyl arm were fatigue and headache.1