Pivotal phase 3 data demonstrated treatment with investigational luspatercept resulted in significant reduction of transfusion burden compared to placebo
Regulatory submissions planned in the United States and Europe in the first half of 2019
SUMMIT, NJ & CAMBRIDGE, MA, USA I December 01, 2018 I Celgene Corporation (NASDAQ: CELG) and Acceleron Pharma Inc. (NASDAQ: XLRN) today announced results from a pivotal, phase 3 trial (BELIEVE) evaluating the safety and efficacy of luspatercept for the treatment of adults with beta-thalassemia-associated anemia who require regular red blood cell (RBC) transfusions. The data were presented by Maria Domenica Cappellini, M.D. in an oral session of the 60th American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego, CA (Abstract #163).
“Currently, the standard of care to help patients with beta-thalassemia manage their anemia is regular, lifelong red blood cell transfusions, which over time can result in iron overload and life-threatening co-morbidities,” said Professor Cappellini, M.D., Professor of Medicine, University of Milan – Fondazione IRCCS. “These findings from the BELIEVE study are exciting because they suggest that luspatercept may help patients reduce their dependence on red blood cell transfusions.”
BELIEVE met the primary endpoint of erythroid response, defined as a ≥33% reduction in RBC transfusion burden (with a reduction of ≥ 2 units of RBC) during weeks 13–24 compared to the baseline 12-week interval prior to randomization. The study also included secondary endpoints that evaluated the impact of treatment on RBC transfusion burden. Mean change in transfusion burden from baseline to weeks 13-24 (luspatercept vs. placebo) was -1.35 RBC units.
RBC Transfusion Burden Reduction of ≥ 33% Response Rates1
| Response Time Interval |
|
|
Luspatercept |
|
|
Placebo |
|
|
P-value |
| Weeks 13-24 |
|
|
21.4% (48/224) |
|
|
4.5% (5/112) |
|
|
< 0.0001 |
| Weeks 37-48 |
|
|
19.6% (44/224) |
|
|
3.6% (4/112) |
|
|
< 0.0001 |
| Any 12 weeks during the entire treatment period |
|
|
70.5% (158/224) |
|
|
29.5% (33/112) |
|
|
< 0.0001 |
| Any 24 weeks during the entire treatment period |
|
|
41.1% (92/224) |
|
|
2.7% (3/112) |
|
|
< 0.0001 |
| |
|
|
|
|
|
|
|
|
|
RBC Transfusion Burden Reduction of ≥ 50% Response Rates1
| Response Time Interval |
|
|
Luspatercept |
|
|
Placebo |
|
|
P-value |
| Weeks 13-24 |
|
|
7.6% (17/224) |
|
|
1.8% (2/112) |
|
|
0.0303 |
| Weeks 37-48 |
|
|
10.3% (23/224) |
|
|
0.9% (1/112) |
|
|
0.0017 |
| Any 12 weeks during the entire treatment period |
|
|
40.2% (90/224) |
|
|
6.3% (7/112) |
|
|
< 0.0001 |
| Any 24 weeks during the entire treatment period |
|
|
16.5% (37/224) |
|
|
0.9% (1/112) |
|
|
< 0.0001 |
| |
|
|
|
|
|
|
|
|
|
1RBC transfusion burden reduction response rates are calculated versus baseline (i.e., the 12 weeks prior to randomization)
BELIEVE Safety Summary (Safety Population)
Grade 3 or higher treatment-emergent adverse events (TEAEs) were reported in 29.1% (65/223) of patients receiving luspatercept and 15.6% (17/109) of patients receiving placebo. Serious adverse events were reported in 15.2% (34/223) of patients receiving luspatercept and 5.5% (6/109) of patients receiving placebo. A TEAE of acute cholecystitis resulted in death in one placebo-treated patient (0.9%). No luspatercept-treated patients died due to TEAEs.
Grade 3 or 4 TEAEs in at least 1% of patients in either arm
| |
|
|
Luspatercept
N= 223
|
|
|
Placebo
N= 109
|
| Anemia |
|
|
3.1% |
|
|
0.0% |
| Increased liver iron concentration |
|
|
2.7% |
|
|
0.9% |
| Hyperuricemia |
|
|
2.7% |
|
|
0.0% |
| Hypertension |
|
|
1.8% |
|
|
0.0% |
| Syncope |
|
|
1.8% |
|
|
0.0% |
| Back pain |
|
|
1.3% |
|
|
0.9% |
| Bone pain |
|
|
1.3% |
|
|
0.0% |
| Blood uric acid increased |
|
|
1.3% |
|
|
0.0% |
| Increased aspartate aminotransferase |
|
|
1.3% |
|
|
0.0% |
| Increase alanine aminotransferase |
|
|
0.9% |
|
|
2.8% |
| Thromboembolic events* |
|
|
0.9% |
|
|
0.0% |
| |
|
|
|
|
|
|
*All grades of thromboembolic events, including DVT, PE, portal vein thrombosis, ischemic stroke, thrombophlebitis, and superficial phlebitis were reported in 8 of 223 (3.6%) luspatercept-treated versus 1 of 109 (0.9%) placebo-treated patients
“The BELIEVE results demonstrate the potential of luspatercept to help adults living with beta-thalassemia better manage their anemia and reduce their transfusion burden,” said Alise Reicin, M.D., President, Global Clinical Development for Celgene. “These results further our understanding of the luspatercept clinical profile, which will continue to inform our plans to advance this promising investigational therapy.”
“These outcomes of the BELIEVE trial increase our confidence in the potential of luspatercept to become an important new treatment option for patients suffering from beta-thalassemia,” said Habib Dable, President and Chief Executive Officer of Acceleron. “Our focus now is to work diligently with health authorities to help ensure that this underserved patient population can gain access to luspatercept as quickly as possible.”
Luspatercept is not approved in any region for any indication. The companies are planning regulatory application submissions of luspatercept in the United States and Europe in the first half of 2019.
About BELIEVE
BELIEVE is a phase 3, randomized, double blind, placebo-controlled multicenter study comparing luspatercept + best supportive care (BSC) versus placebo + BSC in adult beta-thalassemia patients who require regular RBC transfusions. The median age of the patients was 30 years in both treatment arms. 336 patients were randomized 2:1 to receive either luspatercept 1.0 mg/kg + BSC (224 patients) or placebo + BSC (112 patients) every 3 weeks for up to 48 weeks. Patients in the luspatercept + BSC arm were able to be titrated up to 1.25 mg/kg of luspatercept every 3 weeks. BSC was defined as RBC transfusions and iron chelation therapy to maintain each patient’s baseline hemoglobin level. Crossover to the luspatercept treatment group was allowed after unblinding and assessment by an independent Data Safety Monitoring committee; patients receiving luspatercept + BSC will be followed for up to 3 years. The study was conducted at 65 sites in 15 countries.
About Luspatercept
Luspatercept is a first-in-class erythroid maturation agent (EMA) that is believed to regulate late-stage red blood cell maturation. Acceleron and Celgene are jointly developing luspatercept as part of a global collaboration. Phase 3 clinical trials continue to evaluate the safety and efficacy of luspatercept in patients with MDS (the MEDALIST trial) and in patients with beta-thalassemia (the BELIEVE trial). A COMMANDS phase 3 trial in first-line, lower-risk, MDS patients, the BEYOND phase 2 trial in non-transfusion-dependent beta-thalassemia, and a phase 2 trial in myelofibrosis are ongoing. For more information, please visit www.clinicaltrials.gov.
About Celgene
Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global biopharmaceutical company engaged primarily in the discovery, development and commercialization of innovative therapies for the treatment of cancer and inflammatory diseases through next-generation solutions in protein homeostasis, immuno-oncology, epigenetics, immunology and neuro-inflammation. For more information, please visit www.celgene.com.
Follow Celgene on Social Media: Twitter, Pinterest, LinkedIn, Facebook and YouTube.
About Acceleron
Acceleron is a Cambridge-based, clinical-stage biopharmaceutical company dedicated to the discovery, development, and commercialization of therapeutics to treat serious and rare diseases. The Company’s leadership in the understanding of TGF-beta biology and protein engineering generates innovative compounds that engage the body’s ability to regulate cellular growth and repair.
Acceleron focuses its research and development efforts in hematologic, neuromuscular, and pulmonary diseases. In hematology, the Company and its global collaboration partner, Celgene, are developing luspatercept for the treatment of chronic anemia in myelodysplastic syndromes, beta-thalassemia, and myelofibrosis. Acceleron is also advancing its neuromuscular franchise with two distinct Myostatin+ agents, ACE-083 and ACE-2494, and a phase 2 pulmonary program with sotatercept in pulmonary arterial hypertension.
SOURCE: Acceleron Pharma
Post Views: 45
Pivotal phase 3 data demonstrated treatment with investigational luspatercept resulted in significant reduction of transfusion burden compared to placebo
Regulatory submissions planned in the United States and Europe in the first half of 2019
SUMMIT, NJ & CAMBRIDGE, MA, USA I December 01, 2018 I Celgene Corporation (NASDAQ: CELG) and Acceleron Pharma Inc. (NASDAQ: XLRN) today announced results from a pivotal, phase 3 trial (BELIEVE) evaluating the safety and efficacy of luspatercept for the treatment of adults with beta-thalassemia-associated anemia who require regular red blood cell (RBC) transfusions. The data were presented by Maria Domenica Cappellini, M.D. in an oral session of the 60th American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego, CA (Abstract #163).
“Currently, the standard of care to help patients with beta-thalassemia manage their anemia is regular, lifelong red blood cell transfusions, which over time can result in iron overload and life-threatening co-morbidities,” said Professor Cappellini, M.D., Professor of Medicine, University of Milan – Fondazione IRCCS. “These findings from the BELIEVE study are exciting because they suggest that luspatercept may help patients reduce their dependence on red blood cell transfusions.”
BELIEVE met the primary endpoint of erythroid response, defined as a ≥33% reduction in RBC transfusion burden (with a reduction of ≥ 2 units of RBC) during weeks 13–24 compared to the baseline 12-week interval prior to randomization. The study also included secondary endpoints that evaluated the impact of treatment on RBC transfusion burden. Mean change in transfusion burden from baseline to weeks 13-24 (luspatercept vs. placebo) was -1.35 RBC units.
RBC Transfusion Burden Reduction of ≥ 33% Response Rates1
| Response Time Interval |
|
|
Luspatercept |
|
|
Placebo |
|
|
P-value |
| Weeks 13-24 |
|
|
21.4% (48/224) |
|
|
4.5% (5/112) |
|
|
< 0.0001 |
| Weeks 37-48 |
|
|
19.6% (44/224) |
|
|
3.6% (4/112) |
|
|
< 0.0001 |
| Any 12 weeks during the entire treatment period |
|
|
70.5% (158/224) |
|
|
29.5% (33/112) |
|
|
< 0.0001 |
| Any 24 weeks during the entire treatment period |
|
|
41.1% (92/224) |
|
|
2.7% (3/112) |
|
|
< 0.0001 |
| |
|
|
|
|
|
|
|
|
|
RBC Transfusion Burden Reduction of ≥ 50% Response Rates1
| Response Time Interval |
|
|
Luspatercept |
|
|
Placebo |
|
|
P-value |
| Weeks 13-24 |
|
|
7.6% (17/224) |
|
|
1.8% (2/112) |
|
|
0.0303 |
| Weeks 37-48 |
|
|
10.3% (23/224) |
|
|
0.9% (1/112) |
|
|
0.0017 |
| Any 12 weeks during the entire treatment period |
|
|
40.2% (90/224) |
|
|
6.3% (7/112) |
|
|
< 0.0001 |
| Any 24 weeks during the entire treatment period |
|
|
16.5% (37/224) |
|
|
0.9% (1/112) |
|
|
< 0.0001 |
| |
|
|
|
|
|
|
|
|
|
1RBC transfusion burden reduction response rates are calculated versus baseline (i.e., the 12 weeks prior to randomization)
BELIEVE Safety Summary (Safety Population)
Grade 3 or higher treatment-emergent adverse events (TEAEs) were reported in 29.1% (65/223) of patients receiving luspatercept and 15.6% (17/109) of patients receiving placebo. Serious adverse events were reported in 15.2% (34/223) of patients receiving luspatercept and 5.5% (6/109) of patients receiving placebo. A TEAE of acute cholecystitis resulted in death in one placebo-treated patient (0.9%). No luspatercept-treated patients died due to TEAEs.
Grade 3 or 4 TEAEs in at least 1% of patients in either arm
| |
|
|
Luspatercept
N= 223
|
|
|
Placebo
N= 109
|
| Anemia |
|
|
3.1% |
|
|
0.0% |
| Increased liver iron concentration |
|
|
2.7% |
|
|
0.9% |
| Hyperuricemia |
|
|
2.7% |
|
|
0.0% |
| Hypertension |
|
|
1.8% |
|
|
0.0% |
| Syncope |
|
|
1.8% |
|
|
0.0% |
| Back pain |
|
|
1.3% |
|
|
0.9% |
| Bone pain |
|
|
1.3% |
|
|
0.0% |
| Blood uric acid increased |
|
|
1.3% |
|
|
0.0% |
| Increased aspartate aminotransferase |
|
|
1.3% |
|
|
0.0% |
| Increase alanine aminotransferase |
|
|
0.9% |
|
|
2.8% |
| Thromboembolic events* |
|
|
0.9% |
|
|
0.0% |
| |
|
|
|
|
|
|
*All grades of thromboembolic events, including DVT, PE, portal vein thrombosis, ischemic stroke, thrombophlebitis, and superficial phlebitis were reported in 8 of 223 (3.6%) luspatercept-treated versus 1 of 109 (0.9%) placebo-treated patients
“The BELIEVE results demonstrate the potential of luspatercept to help adults living with beta-thalassemia better manage their anemia and reduce their transfusion burden,” said Alise Reicin, M.D., President, Global Clinical Development for Celgene. “These results further our understanding of the luspatercept clinical profile, which will continue to inform our plans to advance this promising investigational therapy.”
“These outcomes of the BELIEVE trial increase our confidence in the potential of luspatercept to become an important new treatment option for patients suffering from beta-thalassemia,” said Habib Dable, President and Chief Executive Officer of Acceleron. “Our focus now is to work diligently with health authorities to help ensure that this underserved patient population can gain access to luspatercept as quickly as possible.”
Luspatercept is not approved in any region for any indication. The companies are planning regulatory application submissions of luspatercept in the United States and Europe in the first half of 2019.
About BELIEVE
BELIEVE is a phase 3, randomized, double blind, placebo-controlled multicenter study comparing luspatercept + best supportive care (BSC) versus placebo + BSC in adult beta-thalassemia patients who require regular RBC transfusions. The median age of the patients was 30 years in both treatment arms. 336 patients were randomized 2:1 to receive either luspatercept 1.0 mg/kg + BSC (224 patients) or placebo + BSC (112 patients) every 3 weeks for up to 48 weeks. Patients in the luspatercept + BSC arm were able to be titrated up to 1.25 mg/kg of luspatercept every 3 weeks. BSC was defined as RBC transfusions and iron chelation therapy to maintain each patient’s baseline hemoglobin level. Crossover to the luspatercept treatment group was allowed after unblinding and assessment by an independent Data Safety Monitoring committee; patients receiving luspatercept + BSC will be followed for up to 3 years. The study was conducted at 65 sites in 15 countries.
About Luspatercept
Luspatercept is a first-in-class erythroid maturation agent (EMA) that is believed to regulate late-stage red blood cell maturation. Acceleron and Celgene are jointly developing luspatercept as part of a global collaboration. Phase 3 clinical trials continue to evaluate the safety and efficacy of luspatercept in patients with MDS (the MEDALIST trial) and in patients with beta-thalassemia (the BELIEVE trial). A COMMANDS phase 3 trial in first-line, lower-risk, MDS patients, the BEYOND phase 2 trial in non-transfusion-dependent beta-thalassemia, and a phase 2 trial in myelofibrosis are ongoing. For more information, please visit www.clinicaltrials.gov.
About Celgene
Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global biopharmaceutical company engaged primarily in the discovery, development and commercialization of innovative therapies for the treatment of cancer and inflammatory diseases through next-generation solutions in protein homeostasis, immuno-oncology, epigenetics, immunology and neuro-inflammation. For more information, please visit www.celgene.com.
Follow Celgene on Social Media: Twitter, Pinterest, LinkedIn, Facebook and YouTube.
About Acceleron
Acceleron is a Cambridge-based, clinical-stage biopharmaceutical company dedicated to the discovery, development, and commercialization of therapeutics to treat serious and rare diseases. The Company’s leadership in the understanding of TGF-beta biology and protein engineering generates innovative compounds that engage the body’s ability to regulate cellular growth and repair.
Acceleron focuses its research and development efforts in hematologic, neuromuscular, and pulmonary diseases. In hematology, the Company and its global collaboration partner, Celgene, are developing luspatercept for the treatment of chronic anemia in myelodysplastic syndromes, beta-thalassemia, and myelofibrosis. Acceleron is also advancing its neuromuscular franchise with two distinct Myostatin+ agents, ACE-083 and ACE-2494, and a phase 2 pulmonary program with sotatercept in pulmonary arterial hypertension.
SOURCE: Acceleron Pharma
Post Views: 45
