Literature Scan selected the higher luspatercept concentrations for the 32 patients who entered the extension study ( 13 LTB and 19 HTB ).
The median duration of treatment for all patients across both the base and extension studies was 6.8 months ( range = 2.0-19.8 months ). At three-month follow-up , 32 of the 51 patients ( 63 %) treated with higher dose concentrations of luspatercept across both the base and extension studies achieved HI-E ( TABLE 3 on page 37 ). Only two of the patients who received lower dose concentrations during the base study achieved HI-E .
The results showed “ a clear dose-dependent efficacy response ,” the authors reported . Across both study stages , HI-E response rates were higher in patients who received higher dose concentrations of luspatercept , compared with those who received lower dose concentrations , for both LTB and HTB patients ( p values not reported ):
• lower dose concentrations : 0 of 2 ( 0 %) LTB patients and 2 of 7 ( 29 %) HTB patients
• higher dose concentrations : 11 of 17 ( 65 %) LTB patients and 21 of 34 ( 62 %) HTB patients
In the extension study , the 13 patients with LTB who received higher dose concentrations “ showed sustained increases from baseline in mean hemoglobin for at least 15 months ,” the authors reported , adding that 11 of these
the full prescribing information ]. PROMACTA was administered to |
330 patients for at least 6 months and 218 patients for at least 1 year . |
Table 4 presents the most common adverse drug reactions ( experienced |
by greater than or equal to 3 % of patients receiving PROMACTA ) from |
the three placebo-controlled trials , with a higher incidence in PROMACTA |
versus placebo . |
Table 4 . Adverse Reactions ( ≥3 %) from Three Placebo-controlled Trials |
in Adults with Chronic Immune ( Idiopathic ) Thrombocytopenia |
|
PROMACTA 50 mg |
Placebo |
|
n = 241 |
n = 128 |
Adverse Reaction |
(%) |
(%) |
Nausea |
9 |
3 |
Diarrhea |
9 |
7 |
Upper respiratory tract infection |
7 |
6 |
Vomiting |
6 |
< 1 |
Increased ALT |
5 |
3 |
Myalgia |
5 |
2 |
Urinary tract infection |
5 |
3 |
Oropharyngeal pain |
4 |
3 |
Increased AST |
4 |
2 |
Pharyngitis |
4 |
2 |
Back pain |
3 |
2 |
Influenza |
3 |
2 |
Paresthesia |
3 |
2 |
Rash |
3 |
2 |
In the three controlled clinical chronic ITP trials , alopecia , musculoskeletal pain , blood alkaline phosphatase increased , and dry mouth were the adverse reactions reported in 2 % of patients treated with PROMACTA and in no patients who received placebo .
Among 302 patients with chronic ITP who received PROMACTA in the single-arm extension trial , the adverse reactions occurred in a pattern similar to that seen in the placebo-controlled trials . Table 5 presents the most common treatment-related adverse reactions ( experienced by greater than or equal to 3 % of patients receiving PROMACTA ) from the extension trial .
Table 5 . Treatment-related Adverse Reactions ( ≥3 %) from Extension Trial in Adults with Chronic Immune ( Idiopathic ) Thrombocytopenia
PROMACTA 50 mg n = 302
Adverse Reaction (%)
Headache 10 ALT increased 5 AST increased 5 Cataract 5 Fatigue 5 Blood bilirubin increased 4 Nausea 4 Hyperbilirubinemia 3 Diarrhea 3
In the three controlled chronic ITP trials , serum liver test abnormalities ( predominantly Grade 2 or less in severity ) were reported in 11 % and 7 % of patients for PROMACTA and placebo , respectively . Four patients ( 1 %) treated with PROMACTA and three patients in the placebo group ( 2 %) discontinued treatment due to hepatobiliary laboratory abnormalities . Seventeen of the patients treated with PROMACTA in the controlled trials with hepatobiliary laboratory abnormalities were re-exposed to PROMACTA in the extension trial . Eight of these patients again experienced liver test abnormalities ( less than or equal to Grade 3 ) resulting in discontinuation of PROMACTA in one patient . In the extension chronic ITP trial , six additional patients had PROMACTA discontinued due to liver test abnormalities ( less than or equal to Grade 3 ).
In clinical trials in patients with chronic ITP , one patient treated with PROMACTA (< 1 %) experienced drug-induced liver injury [ see Warnings and Precautions ( 5.2 )].
In a placebo-controlled trial of PROMACTA in patients with chronic liver disease and thrombocytopenia not related to ITP , six patients treated with PROMACTA and one patient in the placebo group developed portal vein thromboses [ see Warnings and Precautions ( 5.3 )].
Pediatric Patients : The data described below reflect median exposure to |
PROMACTA of 91 days for 107 pediatric patients ( aged 1 to 17 years ) |
with chronic ITP , of whom 53 % were female , across the randomized |
phase of two placebo-controlled trials . |
Table 6 presents the most common adverse drug reactions ( experienced |
by greater than or equal to 3 % of pediatric patients 1 year and older |
receiving PROMACTA ) across the two placebo-controlled trials , with a |
higher incidence for PROMACTA versus placebo . |
Table 6 . Adverse Reactions ( ≥3 %) with a Higher Incidence for PROMACTA |
versus Placebo from Two Placebo-controlled Trials in Pediatric Patients |
1 Year and Older with Chronic Immune ( Idiopathic ) Thrombocytopenia |
|
PROMACTA |
Placebo |
|
n = 107 |
n = 50 |
Adverse Reaction |
(%) |
(%) |
Upper respiratory tract infection |
17 |
6 |
Nasopharyngitis |
12 |
4 |
Cough |
9 |
0 |
Diarrhea |
9 |
2 |
Pyrexia |
9 |
8 |
Rhinitis |
9 |
6 |
Abdominal pain |
8 |
4 |
Oropharyngeal pain |
8 |
2 |
Toothache |
6 |
0 |
ALT increased a |
6 |
0 |
Rash |
5 |
2 |
AST increased |
4 |
0 |
Rhinorrhea |
4 |
0 |
a Includes adverse reactions or laboratory abnormalities > 3 x ULN . |
Chronic Hepatitis C-associated Thrombocytopenia : In the two placebocontrolled |
trials , 955 patients with chronic hepatitis C-associated thrombo - |
cytopenia received PROMACTA . Table 7 presents the most common |
adverse drug reactions ( experienced by greater than or equal to 10 % of |
patients receiving PROMACTA compared with placebo ). |
Table 7 . Adverse Reactions ( ≥10 % and Greater than Placebo ) from Two |
Placebo-controlled Trials in Adults with Chronic Hepatitis C |
|
PROMACTA |
Placebo |
|
+ Peginterferon / Ribavirin |
+ Peginterferon / Ribavirin |
|
n = 955 |
n = 484 |
Adverse Reaction |
(%) |
(%) |
Anemia |
40 |
35 |
Pyrexia |
30 |
24 |
Fatigue |
28 |
23 |
Headache |
21 |
20 |
Nausea |
19 |
14 |
Diarrhea |
19 |
11 |
Decreased appetite |
18 |
14 |
Influenza-like illness |
18 |
16 |
Asthenia |
16 |
13 |
Insomnia |
16 |
15 |
Cough |
15 |
12 |
Pruritus |
15 |
13 |
Chills |
14 |
9 |
Myalgia |
12 |
10 |
Alopecia |
10 |
6 |
Peripheral edema |
10 |
5 |
Rash was reported in 9 % and 7 % of patients receiving PROMACTA and placebo , respectively .
In the two controlled clinical trials in patients with chronic hepatitis C , hyperbilirubinemia was reported in 8 % of patients receiving PROMACTA compared with 3 % for placebo . Total bilirubin greater than or equal to 1.5 x ULN was reported in 76 % and 50 % of patients receiving PROMACTA and placebo , respectively . ALT or AST greater than or equal to 3 x ULN was reported in 34 % and 38 % of patients for PROMACTA and placebo , respectively .