Rare Disease Report

Sotatercept Effective in Improving Anemia in Patients with MPN-Associated Myelofibrosis

DECEMBER 10, 2017
Mathew Shanley
Data presented by Bose Prithviraj, M.D., of the University of Texas MD Anderson Cancer Center at the 59th Annual American Society of Hematology (ASH) Meeting and Exposition in Atlanta concludes that Sotatercept (ACE-011) is effective in patients with myeloproliferative neoplasm (MPN)-associated myelofibrosis (MF) and anemia, both alone and in combination with ruxolitinib.

The new data includes both updated results from the sotatercept monotherapy cohort and first results from the rux-sotatercept combination cohort. Early results from a Phase 2 study (NCT01712308) determining the safety and efficacy of the drug were presented at the ASH Meeting and Exposition in 2016.

MPN-associated myelofibrosis is characterized by a shortage in red blood cells, or anemia, in almost all affected persons. Current treatment options are unsatisfactory, and anemia is notoriously worsened by ruxolitinib, the only U.S. Food and Drug (FDA)-approved therapy for MF. Sotatercept, being jointly developed between Acceleron Pharma and Celgene, is a first-in-class, activing receptor IIA ligand trap. It improves anemia by sequestering TGF-ß superfamily ligans, like growth and differentiation factor 11 (GDF11), both of which suppress terminal erythroid differentiation.

To date, 33 patients have been treated in the trial, 24 of whom belong to the monotherapy cohort, and the remaining 9 who were placed in the ruxolitinib combination cohort. Of the 24 patients in the former, 10 were female and 14 were male, with a range in age between 47 and 83 years and a median age of 66.5 years.

In the monotherapy cohort, median time from diagnosis was 1.2 years with a range of 0.2-5.8 years. Eleven patients received sotatercept at the 0.75 mg/kg dose and 13 received sotatercept at the 1 mg/kg dose. Six of 17 evaluable patients (on study for ≥84 days) responded. Two responses occurred at the 1 mg/kg dose, and 4 at 0.75 mg/kg. Hemoglobin (Hgb) rose by ≥1.5 g/dL in 2 other patients who only received 2 cycles each and were, thus, not evaluable.

Reasons for discontinuation in the monotherapy cohort included: no response in 7 patients, SCT, patient decision, and progressive MF necessitating alternate therapy in 3 patients each, and transformation to AML, hypertension, and unrelated medical complications in 1 patient each.

In the ruxolitinib cohort, median time from diagnosis was 1.9 years with a range of 0.4-11 years, and all patients had received 1-4 prior therapies. Three patients have come off of the study due to a lack of response.

Between the 2 cohorts, 2 patients (1 in each), reported grade 2 bilateral lower limb pain, which could possibly have been related to sotatercept. Hypertension was assumed to have been related to sotatercept in 1 patient. Overall, sotatercept was very well-tolerated, and it was concluded that the drug, as a single agent, is effective in improving anemia in patients with MPN-associated MF.

Enrollment to both cohorts of the trial is still ongoing, as more experience is required in the setting of concurrent ruxolitinib usage. A similarly designed trial (NCT03194542) of a closely related drug, luspatercept (ACE-536), is being planned to open in 2018.

This was an investigator-sponsored trial, and while the data are promising, Acceleron and Celgene have switched to luspatercept for further commercial development in myelofibrosis.

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Prithviraj, B, Daver, N, Pemmaraju, N. 255 Sotatercept (ACE-011) Alone and in Combination with Ruxolitinib in Patients (pts) with Myeloproliferative Neoplasm (MPN)-Associated Myelofibrosis (MF) and Anemia. Presented at the 59th ASH Annual Meeting & Exposition, December 9-12, 2017; Atlanta GA. Session 634. https://ash.confex.com/ash/2017/webprogram/Paper104189.html

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