- The data in the Warnings and Precautions reflect exposure to REBLOZYL as a single agent administered across a range of doses (0.125 mg/kg–1.75 mg/kg) in 571 patients in 4 trials
- The median duration of treatment was similar between the REBLOZYL and placebo arms (63.3 weeks vs 62.1 weeks, respectively)
- Per protocol, patients in the REBLOZYL and placebo arms were to remain on therapy for at least 48 weeks in the double-blind phase of the trial
- Among patients receiving REBLOZYL, 94% were exposed for 6 months or longer and 72% were exposed for >1 year
- Serious adverse reactions occurred in 3.6% of patients on REBLOZYL. Serious adverse reactions reported in 1% of patients were cerebrovascular accident and deep vein thrombosis. A fatal adverse reaction occurred in 1 patient treated with REBLOZYL who died due to an unconfirmed case of acute myeloid leukemia (AML)
- The most common adverse reactions (at least 10% for REBLOZYL and 1% more than placebo) were headache (26%), bone pain (20%), arthralgia (19%), fatigue (14%), cough (14%), abdominal pain (14%), diarrhea (12%), and dizziness (11%)
Adverse drug reactions (>5%) in patients receiving REBLOZYL with a difference between arms of 1% in the BELIEVE trial1
| Adverse reaction
| REBLOZYL
(n = 223) |
Placebo
(n = 109) |
All Grades
n (%) |
Grades ≥3a
n (%) |
All Grades
n (%) |
Grades ≥3
n (%) |
| Musculoskeletal and connective tissue disorders |
| Bone pain |
44 (20) |
3 (1) |
9 (8) |
0 (0) |
| Arthralgia |
43 (19) |
0 (0) |
13 (12) |
0 (0) |
| Infections and infestation |
| Influenza |
19 (9) |
0 (0) |
6 (6) |
0 (0) |
| Viral upper respiratory infection |
14 (6) |
1 (0.4) |
2 (2) |
0 (0) |
| Nervous system disorders |
| Headache |
58 (26) |
1 (<1) |
26 (24) |
1 (1) |
| Dizziness |
25 (11) |
0 (0) |
5 (5) |
0 (0) |
| General disorders and administration site conditions |
| Fatigue |
30 (14) |
0 (0) |
14 (13) |
0 (0) |
| Gastrointestinal disorders |
| Abdominal painb |
31 (14) |
0 (0) |
13 (12) |
0 (0) |
| Diarrhea |
27 (12) |
1 (<1) |
11 (10) |
0 (0) |
| Nausea |
20 (9) |
0 (0) |
6 (6) |
0 (0) |
| Vascular disorders |
| Hypertensionc |
18 (8) |
4 (2) |
3 (3) |
0 (0) |
| Metabolism and nutrition disorders |
| Hyperuricemia |
16 (7) |
6 (3) |
0 (0) |
0 (0) |
| Respiratory, thoracic, and mediastinal disorders |
| Cough |
32 (14) |
0 (0) |
12 (11) |
0 (0) |
aLimited to Grade 3 reactions with the exception of 4 events of Grade 4 hyperuricemia.
bGrouped term includes: Abdominal pain and abdominal pain upper.
cGrouped term includes: Essential hypertension, hypertension, and hypertensive crisis.
- Clinically relevant adverse reactions in <5% of patients include vertigo/vertigo positional, syncope/presyncope, injection site reactions, and hypersensitivity1
Liver function laboratory abnormalities in the BELIEVE trial1
|
REBLOZYL
(n = 223)
n (%) |
Placebo
(n = 109)
n (%) |
| ALT ≥3 × ULN |
26 (12) |
13 (12) |
| AST ≥3 × ULN |
25 (11) |
5 (5) |
| ALP ≥2 × ULN |
17 (8) |
1 (<1) |
| Total bilirubin ≥2 × ULN |
143 (64) |
51 (47) |
| Direct bilirubin ≥2 × ULN |
13 (6) |
4 (4) |
ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; ULN, upper limit of normal.
Immunogenicity1
- Of 284 patients with β-thalassemia who were treated with REBLOZYL and evaluable for the presence of anti-luspatercept-aamt antibodies, 4 patients (1.4%) tested positive for treatment-emergent anti-luspatercept-aamt antibodies, including 2 patients (0.7%) who had neutralizing antibodies
- Luspatercept-aamt serum concentration tended to decrease in the presence of neutralizing antibodies
- There were no severe acute systemic hypersensitivity reactions reported for patients with anti-luspatercept-aamt antibodies in REBLOZYL clinical trials, and there was no association between hypersensitivity type reaction or injection site reaction and presence of anti-luspatercept-aamt antibodies
Lactation1
- REBLOZYL was detected in milk of lactating rats. When a drug is present in animal milk, it is likely that the drug will be present in human milk. There are no data on the presence of REBLOZYL in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in the breastfed child, advise patients that breastfeeding is not recommended during treatment with REBLOZYL, and for 3 months after the last dose
REBLOZYL discontinuations, dose reductions, and dose interruptions in β-thalassemia1
Discontinuations due to adverse reactions1
Permanent discontinuation due to an adverse reaction (Grades 1-4) occurred in 5.4% of patients who received REBLOZYL. Most frequent adverse reactions requiring permanent discontinuation in patients who received REBLOZYL included arthralgia (1%), back pain (1%), bone pain (<1%), and headache (<1%).
Dose reductions and interruptions due to adverse reactions1
Dosage reductions due to an adverse reaction occurred in 2.7% of patients who received REBLOZYL. Most frequent adverse reactions requiring dosage reduction in >0.5% of patients who received REBLOZYL included hypertension and headache.
Dosage interruptions due to an adverse reaction occurred in 15.2% of patients who received REBLOZYL. Most frequent adverse reactions requiring dosage interruption in >1% of patients who received REBLOZYL included upper respiratory tract infection, ALT increase, and cough.
