Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as ACE-536, MK-6143, A536
luspatercept · 5 trials · 4 indications
An adverse event (AE) was any untoward medical occurrence in a participant or clinical investigation participant administered a study drug, which did not necessarily have a causal relationship with the treatment. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it was considered related to the study drug. The number of participants who experienced an AE is reported.
An adverse event (AE) was any untoward medical occurrence in a participant or clinical investigation participant administered a study drug, which did not necessarily have a causal relationship with the treatment. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it was considered related to the study drug. The number of participants who discontinued study treatment due to an AE is reported.
An erythroid response in NTD participants was defined as a mean hemoglobin increase of ≥1.5 g/dL from baseline for ≥14 days in the absence of blood transfusion. Baseline hemoglobin for NTD participants was the average of two or more measurements performed during the screening period. Hemoglobin measurements within 2 weeks following red blood cell (RBC) transfusion or 56 days after the last dose were excluded from analysis. NTD participants were participants who had received \<4 units of RBCs within 8 weeks prior to the first dose of study drug. The percentage of participants with a hemoglobin increase of ≥1.5 g/dL from baseline for ≥14 days is presented.
Transfusion burden for TD participants was defined as the ratio of RBC transfusion units (or milliliters) transfused during a 12-week interval divided by the duration of that interval compared to the ratio of RBC transfusion units 12 weeks prior to the start of treatment (baseline). The interval during the pretreatment period was defined as the 12 weeks prior to the first dose of study drug. An interval during the treatment plus follow-up period was defined as any 12-week interval after the first dose of study drug. TD participants were participants who had received ≥4 units of RBCs every 8 weeks (confirmed over 6 months prior to the first dose of study drug). The percentage of participants with a ≥20% reduction in RBC transfusion burden from baseline is presented.
The mHI-E for LTB participants was defined as a hemoglobin increase of ≥1.5 g/dL from baseline for ≥14 days or rolling 2 weeks (in the absence of red blood cell \[RBC\] transfusions). Hemoglobin measurements within 7 days following RBC transfusion were excluded from analysis. LTB participants were those who received \<4 units of RBCs within 8 weeks prior to baseline. Rolling 2 weeks was defined as any consecutive 2 weeks during the study. The percentage of LTB participants with mHI-E were reported.
The mHI-E for HTB participants was defined as a ≥4 units or ≥50% reduction in RBC transfusion burden during any rolling 8-week window compared to baseline. HTB participants were those who required ≥4 units of RBC transfusions within 8 weeks prior to baseline. Rolling 8 weeks was defined as any consecutive 8 weeks during the study. The percentage of HTB participants with mHI-E were reported.
| Arm | Type | Description |
|---|---|---|
| Luspatercept Extension Population | EXPERIMENTAL | Participants receive luspatercept 0.6, 0.8, 1.0, or 1.25 mg/kg administered by subcutaneous injection on Day 1 of each 21-day cycle for up to 87 cycles (up to approximately 5 years). Participants will receive the highest tolerated dose level of luspatercept that they were assigned in the base study unless a dose modification was required. |
| Luspatercept 0.2 mg/kg | EXPERIMENTAL | Participants receive luspatercept 0.2 mg/kg as a subcutaneous (SC) injection every 3 weeks (Q3W) on Day 1 of each cycle for up to 5 cycles (each cycle length = 21 days). |
| Luspatercept 0.4 mg/kg | EXPERIMENTAL | Participants receive luspatercept 0.4 mg/kg as an SC injection Q3W on Day 1 of each cycle for up to 5 cycles (each cycle length = 21 days). |
| Luspatercept 0.6 mg/kg | EXPERIMENTAL | Participants receive luspatercept 0.6 mg/kg as an SC injection Q3W on Day 1 of each cycle for up to 5 cycles (each cycle length = 21 days). |
| Luspatercept 0.8 mg/kg | EXPERIMENTAL | Participants receive luspatercept 0.8 mg/kg as an SC injection Q3W on Day 1 of each cycle for up to 5 cycles (each cycle length = 21 days). |
| Luspatercept 1.0 mg/kg | EXPERIMENTAL | Participants receive luspatercept 1.0 mg/kg as an SC injection Q3W on Day 1 of each cycle for up to 5 cycles (each cycle length = 21 days). |
| Luspatercept 1.25 mg/kg | EXPERIMENTAL | Participants receive luspatercept 1.25 mg/kg as an SC injection Q3W on Day 1 of each cycle for up to 5 cycles (each cycle length = 21 days). |
| Expansion Cohort | EXPERIMENTAL | Participants receive an initial dose of luspatercept 0.8 mg/kg as an SC injection on Day 1 of Cycle 1 (Cycle length = 21 days). For each subsequent cycle (up to 5 cycles), the dose was titrated up to a maximum dose of 1.25 mg/kg based on the safety review team (SRT) recommendations. |
| Luspatercept 0.125mg/kg (Cohort 1) | EXPERIMENTAL | Participants receive luspatercept 0.125mg/kg as a subcutaneous (SC) injection every 3 weeks (Q3W) on Day 1 of each cycle for up to 5 cycles (each cycle length = 21 days). |
| Luspatercept 0.25mg/kg (Cohort 2) | EXPERIMENTAL | Participants receive luspatercept titrated up to 0.25mg/kg via Fibonacci scheme, SC injection Q3W on Day 1 of each cycle for up to 5 cycles (each cycle length = 21 days). |
| Luspatercept 0.50mg/kg (Cohort 3) | EXPERIMENTAL | Participants receive luspatercept titrated up to 0.50mg/kg via Fibonacci scheme, SC injection Q3W on Day 1 of each cycle for up to 5 cycles (each cycle length = 21 days). |
| Luspatercept 0.75mg/kg (Cohort 4) | EXPERIMENTAL | Participants receive luspatercept titrated up to 0.75mg/kg via Fibonacci scheme, SC injection Q3W on Day 1 of each cycle for up to 5 cycles (each cycle length = 21 days). |
| Luspatercept 1.00mg/kg (Cohort 5) | EXPERIMENTAL | Participants receive luspatercept titrated up to 1.00mg/kg via Fibonacci scheme, SC injection Q3W on Day 1 of each cycle for up to 5 cycles (each cycle length = 21 days). |
| Luspatercept 1.33mg/kg (Cohort 6) | EXPERIMENTAL | Participants receive luspatercept titrated up to 1.33mg/kg via Fibonacci scheme, SC injection Q3W on Day 1 of each cycle for up to 5 cycles (each cycle length = 21 days). |
| Luspatercept 1.75mg/kg (Cohort 7) | EXPERIMENTAL | Participants receive luspatercept titrated up to 1.75mg/kg via Fibonacci scheme, SC injection Q3W on Day 1 of each cycle for up to 5 cycles (each cycle length = 21 days). |
| ACE-536 | EXPERIMENTAL | Subjects assigned to 1 of 5 possible dosing groups. |
| Placebo | PLACEBO_COMPARATOR | - |
| Name | Type | Description |
|---|---|---|
| luspatercept | DRUG | subcutaneous injection |
| ACE-536 | BIOLOGICAL | Subjects receive a total of 2 subcutaneous doses of ACE-536 on Day 1 and Day 15. |
| Placebo | OTHER | Subjects receive a total of 2 subcutaneous doses of placebo on Day 1 and Day 15. |
The main inclusion and exclusion criteria include but are not limited to the following: Inclusion Criteria: * Completion of the treatment period in the base study A536-04. * Females of child- bearing potential (defined as sexually mature women who have not undergone hysterectomy or bilateral oopho...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Bristol-Myers Squibb Company | BMY | 2 | PHASE3 | Luspatercept |
| Takeda Pharmaceutical Co. Ltd. Sponsored ADR | TAK | 2 | PHASE3 | Elritercept |
| Disc Medicine, Inc. | IRON | 2 | PHASE2 | DISC-0974 |
| Akebia Therapeutics, Inc. | AKBA | 2 | PHASE3 | Vadadustat |
| Ascentage Pharma Group International Unsponsored ADR | AAPG | 1 | PHASE1 | APG-5918 |
| Bayer | BAYRY | 1 | - | Molidustat |
Luspatercept is being studied for the treatment of anemia in adults with beta-thalassemia and myelodysplastic syndromes. Clinical development has focused on patients with B-thalassemia, beta-thalassemia, and anemia associated with myelodysplastic syndromes, with trial participants aged 18 years and older.
Luspatercept targets TGFB1, TGFB2, and TGFB3, acting as an inhibitor of these TGF-beta signaling proteins. By inhibiting this pathway, the drug is designed to promote late-stage red blood cell maturation, which is the rationale behind its study in anemias such as beta-thalassemia and myelodysplastic syndromes.
Luspatercept is being developed by Merck & Company, Inc., which trades under the ticker MRK. The clinical program includes Phase 2 studies conducted in Greece, Italy, and Germany in patients with beta-thalassemia and myelodysplastic syndromes.
Luspatercept is in Phase 2 clinical development for its studied hematology indications. It is investigational and has not been approved for these uses based on the available development information. The Phase 2 program includes completed studies in beta-thalassemia and myelodysplastic syndromes.
Luspatercept has been evaluated in completed Phase 2 trials including NCT01749514 in anemia and myelodysplastic syndrome, NCT01749540 in beta-thalassemia, NCT02268383 in myelodysplastic syndromes, and NCT02268409 in beta-thalassemia. These studies enrolled adults aged 18 and older across sites in Germany, Greece, and Italy.
Yes, luspatercept is also known as ACE-536. The alternative name appears in the trial title for NCT01749540, which evaluated luspatercept (ACE-536) in participants with beta-thalassemia. Both names refer to the same investigational agent being developed by Merck & Company, Inc.