Celgene Corporation CELG and Acceleron Pharma Inc. XLRN
today announced preliminary data from ongoing phase 2 clinical trials in
patients with lower risk myelodysplastic syndromes (MDS) at the 56^th American
Society of Hematology (ASH) Annual Meeting and Exposition. In his oral
presentation, Dr. Uwe Platzbecker showed that patients with lower risk MDS
treated with luspatercept achieved increased hemoglobin levels and transfusion
independence. In a separate poster presentation, Dr. Rami Komrokji showed that
lower risk MDS patients who were treated with sotatercept also achieved
increased hemoglobin levels and transfusion independence. Celgene and
Acceleron are jointly developing luspatercept and sotatercept.
“These results in lower risk MDS patients are very exciting,” said Uwe
Platzbecker, M.D., Professor of Hematology and Head of the MDS program at the
University Hospital in Dresden, Germany and coordinating principal
investigator of the luspatercept PACE-MDS study. “Sotatercept and luspatercept
may be useful early in the treatment of lower risk MDS patients, either as the
initial treatment for anemia or in patients who do not respond or become
refractory to treatment with ESAs. These investigational therapeutics have
been very well-tolerated and therefore have the potential to benefit many MDS
patients.”
Luspatercept Data Presented at ASH
In this study, luspatercept was evaluated in patients with low- or
intermediate-1 risk MDS.
A total of 26 patients were treated in this dose-finding stage of the study in
which luspatercept was administered subcutaneously once every 3 weeks for up
to 5 doses (16 weeks) at doses of 0.125 (n=3), 0.25 (n=3), 0.5 (n=3), 0.75
(n=6), 1.0 (n=3) 1.33 (n=6), or 1.75 (n=2) mg/kg. Of these 26 patients, 19 had
a high transfusion burden (≥4 units RBC/8 weeks) and 7 had a low transfusion
burden (<4 units RBC/8 weeks). 54% of patients had been treated previously
with erythropoiesis stimulating agents (ESA) and 19% of patients had
previously been treated with lenalidomide.
Low Transfusion Burden (LTB) Patients:
* 4 of 5 (80%) LTB patients treated with doses of 0.75-1.75 mg/kg of
luspatercept achieved the primary endpoint of hemoglobin increase ≥1.5
g/dL for ≥2 weeks in this 16 week study
* Additionally, 2 of 5 (40%) of LTB patients achieved the International
Working Group (IWG) Hematologic Improvement Erythroid (HI-E) response
criteria of a hemoglobin increase ≥1.5 g/dL for ≥8 weeks
* The mean maximum change for patients treated with luspatercept doses of
0.75. and 1.75 mg/kg was 2.2 and 3.5 g/dL, respectively
* All 5 LTB patients treated with luspatercept doses of 0.75-1.75 mg/kg had
received prior ESA
High Transfusion Burden (HTB) Patients:
* 5 of 12 (42%) HTB patients treated with luspatercept doses of 0.75-1.75
mg/kg of achieved IWG HI-E criteria of a reduction of ≥4 units RBC over 8
weeks
* 3 of 12 (25%) HTB patients treated with luspatercept doses of 0.75-1.75
mg/kg achieved transfusion independence for ≥8 weeks
Emerging markers of response:
* As published earlier this year in Nature Medicine, the murine analog of
luspatercept, RAP-536, can correct ineffective erythropoiesis in a mouse
model of MDS
* Splicing factor 3B1 (SF3B1) mutations are seen commonly in MDS patients
with ring sideroblasts and are associated with ineffective erythropoiesis
* Erythroid response (HI-E, IWG) was achieved in 41% of patients treated at
≥0.75 mg/kg. Erythroid response (HI-E, IWG) was achieved in 67% of
patients with ring sideroblasts and SF3B1 mutations
The most common adverse events were diarrhea, muscle spasms, bone pain,
fatigue, myalgia and nasopharyngitis. There were no drug-related serious
adverse events. There was one possibly related grade 3 adverse event of blast
cell count increase.
Sotatercept Data Presented at ASH
A second phase 2 study evaluated sotatercept in patients with low- or
intermediate-1 risk MDS.
A total of 54 patients were treated in this dose-finding study in which
sotatercept was administered subcutaneously once every 3 weeks at doses of 0.1
(n=7), 0.3 (n=6), 0.5 (n=21), and 1.0 (n=20) mg/kg. Of these 54 patients, 46
(85%) had a high transfusion burden (≥4 units RBC/8 weeks) and 8 (15%) had a
low transfusion burden (<4 units RBC/8 weeks). 96% of patients had prior ESA,
57% had a prior hypomethylating agent, and 48% had prior lenalidomide.
Low Transfusion Burden (LTB) Patients:
* 5 (63%) patients achieved a mean hemoglobin increase ≥1.5 g/dL and
transfusion independence sustained for ≥ 8 weeks
* Duration of transfusion independence ranged from 76 to 233 days
* Maximum mean hemoglobin increases ranged from 1.9 to 4.4 g/dL
High Transfusion Burden (HTB) Patients:
* 19 of 45 HTB patients (42%) achieved IWG HI-E criteria of a reduction ≥4
RBC units/8 weeks
* 5 HTB patients (11%) achieved transfusion independence
* Duration of transfusion independence ranged from 59 to 345+ days
The most common adverse events were fatigue/asthenia, headache, decreased
appetite, nausea and dyspnea. 3 of 54 (6%) patients discontinued due to
treatment emergent adverse events considered related to sotatercept. 1 patient
with grade 2 hemolytic anemia; 1 patient with grade 3 hypertension; and 1
patient with grade 2 muscle weakness in the 0.3, 0.5, and 1.0 mg/kg dose
groups, respectively.
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