Reblozyl

5 WARNINGS AND PRECAUTIONS • Thrombosis/Thromboembolism: Increased risk in patients with beta thalassemia. Monitor patients for signs and symptoms of thromboembolic events and institute treatment promptly ( 5.1 ). • Hypertension: Monitor blood pressure (BP) during treatment. Initiate anti-hypertensive treatment if necessary ( 5.2 ). • Extramedullary Hematopoietic (EMH) Masses: Increased risk in patients with beta thalassemia. Monitor patients for symptoms and signs or complications resulting from the EMH masses. Treat according to clinical guidelines and discontinue treatment in case of serious complications due to EMH masses ( 5.3 ). • Embryo-Fetal Toxicity: May cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and use of effective contraception ( 5.4 , 8.1 , 8.3 ). 5.1 Thrombosis/Thromboembolism In adult patients with beta thalassemia, thromboembolic events (TEE) were reported in 8/223 (3.6%) REBLOZYL-treated patients. Reported TEEs included deep vein thromboses, pulmonary embolus, portal vein thrombosis, and ischemic strokes. Patients with known risk factors for thromboembolism, e.g. splenectomy or concomitant use of hormone replacement therapy, may be at further increased risk of thromboembolic conditions. Consider thromboprophylaxis in patients with beta thalassemia at increased risk of TEE. Monitor patients receiving REBLOZYL for signs and symptoms of thromboembolic events and institute treatment promptly. 5.2 Hypertension Hypertension was reported in 63/554 (11.4%) of REBLOZYL-treated patients. Across clinical studies, the incidence of Grade 3-4 hypertension ranged from 2% to 9.6%. In adult patients with beta thalassemia with normal baseline blood pressure, 13 (6.2%) patients developed systolic blood pressure (SBP) ≥130 mm Hg and 33 (16.6%) patients developed diastolic blood pressure (DBP) ≥80 mm Hg. In ESA-refractory or -intolerant adult patients with MDS with normal baseline blood pressure, 26 (30%) patients developed SBP ≥130 mm Hg and 23 (16%) patients developed DBP ≥80 mm Hg. In ESA-naïve adult patients with MDS with normal baseline blood pressure, 23 (36%) patients developed SBP ≥140 mm Hg and 11 (6%) patients developed DBP ≥80 mm Hg. Monitor blood pressure prior to each administration. Manage new-onset hypertension or exacerbations of preexisting hypertension using anti-hypertensive agents. 5.3 Extramedullary Hematopoietic Masses In adult patients with transfusion dependent beta thalassemia, EMH masses were observed in 3.2% of REBLOZYL-treated patients, with spinal cord compression symptoms due to EMH masses occurring in 1.9% of patients (BELIEVE and REBLOZYL long-term follow-up study). In a study of adult patients with non-transfusion dependent beta thalassemia, a higher incidence of EMH masses was observed in 6.3% of REBLOZYL-treated patients vs. 2% of placebo-treated patients in the double-blind phase of the study, with spinal cord compression due to EMH masses occurring in 1 patient with a prior history of EMH. REBLOZYL is not indicated for use in patients with non-transfusion dependent beta-thalassemia. Possible risk factors for the development of EMH masses in patients with beta thalassemia include history of EMH masses, splenectomy, splenomegaly, hepatomegaly, or low baseline hemoglobin (<8.5 g/dL). Signs and symptoms may vary depending on the anatomical location. Monitor patients with beta thalassemia at initiation and during treatment for symptoms and signs or complications resulting from the EMH masses and treat according to clinical guidelines. Discontinue treatment with REBLOZYL in case of serious complications due to EMH masses. Avoid use of REBLOZYL in patients requiring treatment to control the growth of EMH masses. 5.4 Embryo-Fetal Toxicity Based on findings from animal reproductive studies, REBLOZYL may cause fetal harm when administered to a pregnant woman. In animal reproduction studies, administration of luspatercept-aamt to pregnant rats and rabbits during organogenesis resulted in adverse developmental outcomes including increased embryo-fetal mortality, alterations to growth, and structural abnormalities at exposures (based on area under the curve [AUC]) above those occurring at the maximum recommended human dose (MRHD) of 1.75 mg/kg. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use an effective method of contraception during treatment with REBLOZYL and for at least 3 months after the final dose [see Use in Specific Populations ( 8.1 , 8.3 )] .

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: • Thrombosis/Thromboembolism [see Warnings and Precautions ( 5.1 )] • Hypertension [see Warnings and Precautions ( 5.2 )] • Extramedullary Hematopoietic Masses [see Warnings and Precautions ( 5.3 )] The most common (>10%) adverse reactions were fatigue, headache, musculoskeletal pain, arthralgia, dizziness/vertigo, nausea, diarrhea, cough, abdominal pain, dyspnea, COVID-19, edema peripheral, hypertension, and hypersensitivity ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Bristol-Myers Squibb at 1-888-423-5436 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. 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 to 1.75 mg/kg) in 571 patients in 4 trials. Beta Thalassemia The safety of REBLOZYL in patients with beta thalassemia was evaluated in the BELIEVE trial [see Clinical Studies ( 14.1 )] . Key eligibility criteria included adult patients with beta thalassemia (with the exception of patients with hemoglobin S or alpha-thalassemia disease) without major organ damage or recent DVT stroke and platelet counts less than or equal to 1000 x 10 9 /L. Patients received a starting dose of REBLOZYL 1 mg/kg subcutaneous injection every 3 weeks. Overall, 53% of patients had their dose increased to 1.25 mg/kg (46% REBLOZYL, n = 223) or placebo (66%, n = 109). 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 greater than one year. The median age of patients who received REBLOZYL was 30 years (range: 18, 66); 59% female; 54% White and 36% Asian. 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 one patient treated with REBLOZYL who died due to an unconfirmed case of AML (M6). 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%). 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. 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%). Table 7 summarizes the adverse reactions in BELIEVE. Table 7: Adverse Drug Reactions (>5%) in Patients with Beta Thalassemia Receiving REBLOZYL with a Difference Between Arms of 1% in BELIEVE Trial Body System REBLOZYL (N=223) Placebo (N=109) Adverse Reaction All Grades n (%) Grades ≥3 a n (%) All Grades n (%) Grades ≥3 n (%) a Limited to Grade 3 reactions with the exception of 4 events of Grade 4 hyperuricemia. b Grouped term includes abdominal pain and abdominal pain upper. c Grouped term includes essential hypertension, hypertension, and hypertensive crisis. 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 Pain b 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 Hypertension c 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) Clinically relevant adverse reactions in <5% of patients include vertigo/vertigo positional, syncope/presyncope, injection site reactions, hypersensitivity, extramedullary hematopoietic masses, and spinal cord compression. Liver function abnormalities in the BELIEVE trial are shown in Table 8. Table 8: Liver Function Laboratory Abnormalities in Patients with Beta Thalassemia in the BELIEVE Trial 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) Treatment of Myelodysplastic Syndromes Associated Anemia in ESA-naïve Patients The safety of REBLOZYL in patients with very low‑ to intermediate‑risk myelodysplastic syndromes was evaluated in the COMMANDS trial in 356 randomized patients [see Clinical Studies ( 14.2 )] . Key eligibility criteria included adult patients who were ESA‑naïve with endogenous sEPO levels of < 500 U/L and who required regular RBC transfusions. The median time on treatment with REBLOZYL was 41.6 weeks (range, 0 – 165 weeks); 71.3% of patients were exposed for 24 weeks and 45.5% completed 48 weeks of treatment. Among the 178 patients treated with REBLOZYL, 17 (9.6%) discontinued due to an adverse reaction, 48 (27%) had a dose interruption due to an adverse reaction, and 5 (2.8%) had a dose reduction due to an adverse reaction. The most common (>10%) all‑grade adverse reactions included diarrhea, fatigue, hypertension, edema peripheral, nausea, and dyspnea. The most common (>2%) Grade > 3 adverse reactions included hypertension and dyspnea. Selected laboratory abnormalities that changed from Grade 0‑2 at baseline to Grade > 2 at any time during the studies in at least 10% of patients were glomerular filtration rate and total bilirubin increased. Table 9 shows the most common adverse reactions for patients treated with REBLOZYL or epoetin alfa in the COMMANDS trial [see Clinical Studies ( 14.2 )] . Table 9: Adverse Reactions (≥5%) in Patients Receiving REBLOZYL in COMMANDS Trial a Reaction includes similar/grouped terms. b Includes asthenic conditions. Body System /Adverse Reaction REBLOZYL (N=178) Epoetin Alfa (N=176) All Grades n (%) Grade ≥3 n (%) All Grades n (%) Grade ≥3 n (%) General disorders and administration site conditions Fatigue a,b 38 (22) 0 (0) 12 (7) 0 (0) Edema peripheral 23 (13) 0 (0) 12 (7) 0 (0) Non-cardiac chest pain 9 (5) 1 (1) 6 (3) 0 (0) Pyrexia 9 (5) 1 (1) 12 (7) 1 (1) Gastrointestinal disorders Diarrhea 26 (15) 0 (0) 20 (11) 0 (0) Nausea 21 (12) 0 (0) 13 (7) 0 (0) Vascular disorders Hypertension a 25 (14) 17 (10) 13 (7) 9 (5) Respiratory, thoracic and mediastinal disorders Dyspnea 21 (12) 7 (4) 13 (7) 2 (1) Dyspnea exertional 9 (5) 0 (0) 1 (1) 0 (0) Nervous system disorders Dizziness 16 (9) 1 (1) 15 (9) 0 (0) Headache 15 (8) 0 (0) 12 (7) 1 (1) Musculoskeletal and connective tissue disorders Back Pain 16 (9) 2 (1) 13 (7) 3 (2) Arthralgia 10 (6) 0 (0) 14 (8) 0 (0) Myalgia 9 (5) 0 (0) 5 (3) 0 (0) Osteoarthritis 9 (5) 1 (1) 4 (2) 0 (0) Infections and infestations COVID-19 19 (11) 6 (3) 17 (10) 2 (1) Urinary tract infection 13 (7) 0 (0) 7 (4) 0 (0) Pneumonia 8 (5) 7 (4) 15 (9) 11 (6) Metabolism and nutrition disorders Hyperuricemia 12 (7) 1 (1) 10 (6) 1 (1) Decreased appetite 8 (5) 0 (0) 11 (6) 0 (0) Blood and lymphatic system disorders Thrombocytopenia 11 (6) 7 (4) 3 (2) 1 (1) Neutropenia 9 (5) 7 (4) 13 (7) 10 (6) Psychiatric disorders Insomnia 9 (5) 0 (0) 6 (3) 0 (0) Other clinically relevant adverse reactions reported in <5% of patients are injection site reactions, including erythema, pruritus, and rash. Shifts from Grades 0‑2 at baseline to Grades 2‑3 abnormalities for selected laboratory tests in the COMMANDS trial are shown in Table 10. Table 10: Selected Treatment‑Emergent Laboratory Abnormalities in COMMANDS Trial that Shift to Grades 2‑3 a Number of patients at Grades 0-1 at baseline. b GFR= glomerular filtration rate (mL/min) Parameter REBLOZYL Epoetin Alfa N a n (%) N a n (%) Total bilirubin 171 38 (22) 165 19 (12) GFR b 171 60 (35) 167 36 (22) Myelodysplastic Syndromes with Ring Sideroblasts or Myelodysplastic / Myeloproliferative Neoplasm with Ring Sideroblasts and Thrombocytosis Associated Anemia in ESA-refractory or -intolerant patients The safety of REBLOZYL at the recommended dose and schedule was evaluated in 242 patients with MDS with ring sideroblasts (n=192) or other myeloid neoplasms (n=50) in the MEDALIST trial. The safety population included 63% males and 37% females of median age 72 years (range, 30 – 95 years); of these patients, 81% were White, 0.4% Black, 0.4% Other, and race was not reported in 18.2% of patients. The median time on treatment with REBLOZYL was 50.4 weeks (range, 3 – 221 weeks); 67% of patients were exposed for 6 months or longer and 49% were exposed for greater than one year. Among the 242 patients treated with REBLOZYL, 5 (2.1%) had a fatal adverse reaction, 11 (4.5%) discontinued due to an adverse reaction, and 7 (2.9%) had a dose reduction due to an adverse reaction. The most common (≥10%) all-grade adverse reactions included fatigue, musculoskeletal pain, dizziness, diarrhea, nausea, hypersensitivity reactions, hypertension, headache, upper respiratory tract infection, bronchitis, and urinary tract infection. The most common (≥2%) Grade ≥ 3 adverse reactions included fatigue, hypertension, syncope and musculoskeletal pain. Selected laboratory abnormalities that changed from Grade 0-1 at baseline to Grade ≥ 2 at any time during the studies in at least 10% of patients included creatinine clearance decreased, total bilirubin increased, and ALT increased. Table 11 shows the most common adverse reactions for patients treated with REBLOZYL or placebo through the first 8 cycles in the MEDALIST trial [see Clinical Studies ( 14.3 )] . Table 11: Adverse Reactions (≥5%) in Patients Receiving REBLOZYL with a Difference Between Arms of >2% in MEDALIST Trial Through Cycle 8 Body System /Adverse Reaction REBLOZYL (N=153) Placebo (N=76) All Grades n (%) Grade 3 n (%) All Grades n (%) Grade 3 n (%) a Includes asthenic conditions. b Reaction includes similar/grouped terms. General disorders and administration site conditions Fatigue a, b 63 (41) 11 (7) 17 (22) 2 (3) Musculoskeletal and connective tissue disorders Musculoskeletal pain b 30 (20) 3 (2) 11 (14) 0 (0) Nervous system disorders Dizziness/vertigo 28 (18) 1 (<1) 5 (7) 1 (1) Headache b 21 (14) 0 (0) 5 (7) 0 (0) Syncope / presyncope 8 (5) 5 (3) 0 (0) 0 (0) Gastrointestinal disorders Nausea b 25 (16) 1 (<1) 8 (11) 0 (0) Diarrhea b 25 (16) 0 (0) 7 (9) 0 (0) Respiratory, thoracic and mediastinal disorder Dyspnea b 20 (13) 2 (1) 4 (5) 1 (1) Immune system disorders Hypersensitivity reactions b 15 (10) 1 (<1) 5 (7) 0 (0) Renal and urinary disorders Renal impairment b 12 (8) 3 (2) 3 (4) 0 (0) Cardiac disorders Tachycardia b 12 (8) 0 (0) 1 (1) 0 (0) Injury poisoning and procedural complications Injection site reactions 10 (7) 0 (0) 3 (4) 0 (0) Infections and infestations Upper respiratory tract infection 10 (7) 1 (<1) 2 (3) 0 (0) Influenza / influenza like illness 9 (6) 0 (0) 2 (3) 0 (0) Other clinically relevant adverse reactions reported in <5% of patients include bronchitis, urinary tract infection, and hypertension [see Warnings and Precautions ( 5.2 )] . Shifts from Grades 0-1 to Grades 2-4 abnormalities for selected laboratory tests during the first 8 cycles in the MEDALIST trial are shown in Table 12. Table 12: Selected Grades 2-4 Treatment-Emergent Laboratory Abnormalities Through Cycle 8 in the MEDALIST Trial a Number of patients at Grades 0-1 at baseline. Parameter REBLOZYL Placebo N a n (%) N a n (%) ALT elevated 151 13 (9) 74 5 (7) AST elevated 152 6 (4) 76 0 (0) Total bilirubin elevated 140 17 (12) 66 3 (5) Creatinine clearance reduced 113 30 (27) 62 13 (21)

<table ID="_RefTable6" width="100%"><caption>Table 7: Adverse Drug Reactions (&gt;5%) in Patients with Beta Thalassemia Receiving REBLOZYL with a Difference Between Arms of 1% in BELIEVE Trial</caption><col width="35%"/><col width="16%"/><col width="16%"/><col width="16%"/><col width="16%"/><thead><tr><th align="left" styleCode="Rrule Lrule Toprule " valign="bottom"><content styleCode="bold">Body System</content></th><th align="center" colspan="2" styleCode="Rrule Botrule Toprule " valign="top"><content styleCode="bold">REBLOZYL</content> <content styleCode="bold">(N=223)</content></th><th align="center" colspan="2" styleCode="Rrule Botrule Toprule " valign="top"><content styleCode="bold">Placebo</content> <content styleCode="bold">(N=109)</content></th></tr><tr><th align="left" styleCode="Rrule Lrule Botrule " valign="top"><content styleCode="bold"> Adverse Reaction</content></th><th align="center" styleCode="Rrule Botrule " valign="top"><content styleCode="bold">All Grades</content> <content styleCode="bold">n (%)</content></th><th align="center" styleCode="Rrule Botrule " valign="top"><content styleCode="bold">Grades &#x2265;3^a</content> <content styleCode="bold">n (%)</content></th><th align="center" styleCode="Rrule Botrule " valign="top"><content styleCode="bold">All Grades</content> <content styleCode="bold">n (%)</content></th><th align="center" styleCode="Rrule Botrule " valign="top"><content styleCode="bold">Grades &#x2265;3</content> <content styleCode="bold">n (%)</content></th></tr></thead><tfoot><tr><td align="left" colspan="5" valign="top">^a Limited to Grade 3 reactions with the exception of 4 events of Grade 4 hyperuricemia. ^b Grouped term includes abdominal pain and abdominal pain upper. ^c Grouped term includes essential hypertension, hypertension, and hypertensive crisis.</td></tr></tfoot><tbody><tr><td colspan="5" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">Musculoskeletal and connective tissue disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Bone Pain</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>44 (20)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>3 (1)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>9 (8)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Arthralgia</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>43 (19)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>13 (12)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0)</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Infections and infestation</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Influenza</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>19 (9)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>6 (6)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Viral Upper Respiratory Infection</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>14 (6)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>1 (0.4)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>2 (2)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0)</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Nervous system disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Headache</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>58 (26)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>1 (&lt;1)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>26 (24)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>1 (1)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Dizziness</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>25 (11)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>5 (5)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0)</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">General disorders and administration site conditions</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Fatigue</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>30 (14)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>14 (13)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0)</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Gastrointestinal disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Abdominal Pain ^b</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>31 (14)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>13 (12)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Diarrhea</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>27 (12)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>1 (&lt;1)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>11 (10)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Nausea</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>20 (9)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>6 (6)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0)</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Vascular disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Hypertension ^c</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>18 (8)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>4 (2)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>3 (3)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0)</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Metabolism and nutrition disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Hyperuricemia</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>16 (7)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>6 (3)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0)</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Respiratory, thoracic and mediastinal disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule " valign="top"><paragraph> Cough</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>32 (14)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>12 (11)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0)</paragraph></td></tr></tbody></table>

<table ID="_RefTable7" width="100%"><caption>Table 8: Liver Function Laboratory Abnormalities in Patients with Beta Thalassemia in the BELIEVE Trial</caption><col width="50%"/><col width="25%"/><col width="25%"/><thead><tr><th align="left" styleCode="Rrule Botrule Lrule Toprule " valign="top"/><th align="center" styleCode="Rrule Botrule Toprule " valign="top"><content styleCode="bold">REBLOZYL</content> <content styleCode="bold">N = 223</content> <content styleCode="bold">n (%)</content></th><th align="center" styleCode="Rrule Botrule Toprule " valign="top"><content styleCode="bold">Placebo</content> <content styleCode="bold">N = 109</content> <content styleCode="bold">n (%)</content></th></tr></thead><tbody><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>ALT &#x2265; 3 &#xD7; ULN</paragraph></td><td align="center" styleCode="Rrule Toprule Botrule " valign="top"><paragraph>26 (12)</paragraph></td><td align="center" styleCode="Rrule Toprule Botrule " valign="top"><paragraph>13 (12)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>AST &#x2265; 3 &#xD7; ULN</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>25 (11)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>5 (5)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>ALP &#x2265; 2 &#xD7; ULN</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>17 (8)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>1 (&lt;1)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Total bilirubin &#x2265; 2 &#xD7; ULN</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>143 (64)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>51 (47)</paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule " valign="top"><paragraph>Direct bilirubin &#x2265; 2 &#xD7; ULN</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>13 (6)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>4 (4)</paragraph></td></tr></tbody></table>

<table styleCode="Noautorules" width="100%"><caption>Table 9: Adverse Reactions (&#x2265;5%) in Patients Receiving REBLOZYL in COMMANDS Trial</caption><col width="33%"/><col width="16%"/><col width="16%"/><col width="16%"/><col width="16%"/><tfoot><tr><td align="left" colspan="5" valign="top">^a Reaction includes similar/grouped terms.</td></tr><tr><td align="left" colspan="5" valign="top">^b Includes asthenic conditions.</td></tr></tfoot><tbody><tr><td rowspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">Body System /Adverse Reaction</content></paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">REBLOZYL</content></paragraph><paragraph><content styleCode="bold">(N=178)</content></paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">Epoetin Alfa</content></paragraph><paragraph><content styleCode="bold">(N=176)</content></paragraph></td></tr><tr><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">All Grades</content></paragraph><paragraph><content styleCode="bold">n (%)</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">Grade &#x2265;3</content></paragraph><paragraph><content styleCode="bold">n (%)</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">All Grades</content></paragraph><paragraph><content styleCode="bold">n (%)</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">Grade &#x2265;3</content></paragraph><paragraph><content styleCode="bold">n (%)</content></paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">General disorders and administration site conditions</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Fatigue ^a,b</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>38 (22)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>12 (7)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Edema peripheral</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>23 (13)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>12 (7)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Non-cardiac chest pain</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>9 (5)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1 (1)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>6 (3)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Pyrexia</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>9 (5)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1 (1)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>12 (7)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1 (1)</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Gastrointestinal disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Diarrhea</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>26 (15)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>20 (11)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Nausea</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>21 (12)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>13 (7)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0)</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Vascular disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Hypertension ^a</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>25 (14)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>17 (10)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>13 (7)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>9 (5)</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Respiratory, thoracic and mediastinal disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Dyspnea</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>21 (12)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>7 (4)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>13 (7)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2 (1)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Dyspnea exertional</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>9 (5)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1 (1)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0)</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Nervous system disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Dizziness</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>16 (9)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1 (1)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>15 (9)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Headache</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>15 (8)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>12 (7)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1 (1)</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Musculoskeletal and connective tissue disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Back Pain</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>16 (9)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2 (1)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>13 (7)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>3 (2)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Arthralgia</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>10 (6)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>14 (8)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Myalgia</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>9 (5)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>5 (3)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Osteoarthritis</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>9 (5)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1 (1)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>4 (2)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0)</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Infections and infestations</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>COVID-19</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>19 (11)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>6 (3)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>17 (10)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2 (1)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Urinary tract infection</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>13 (7)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>7 (4)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Pneumonia</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>8 (5)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>7 (4)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>15 (9)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>11 (6)</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Metabolism and nutrition disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Hyperuricemia</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>12 (7)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1 (1)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>10 (6)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1 (1)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Decreased appetite</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>8 (5)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>11 (6)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0)</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Blood and lymphatic system disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Thrombocytopenia</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>11 (6)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>7 (4)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>3 (2)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1 (1)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Neutropenia</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>9 (5)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>7 (4)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>13 (7)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>10 (6)</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Psychiatric disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>Insomnia</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>9 (5)</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>0 (0)</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>6 (3)</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>0 (0)</paragraph></td></tr></tbody></table>