Rare Disease Report

Mast Therapeutics Begins Pivotal Phase 3 Study in Children with Sickle Cell Disease

SEPTEMBER 25, 2013

Sickle cell disease is a rare genetic condition that affects 90,000 to 100,000 Americans, mostly African Americans.  A person with sickle cell disease have red blood cells that are hard, sticky, and C-shaped (like the farm tool the "sickle"). These cells clog smaller blood vessels resulting in pain as well as increased risk for infection, acute chest syndrome and stroke.

At present, treatment for this condition includes hydroxyurea (Droxia, Hydrea) to reduce the frequency of painful crises and when necessary, blood transfusions are performed. Pain crises may benefit from over-the-counter pain medications, rest, and oxygen therapy but these crises are a common and expensive problem. One study by Kauf et al (2009) found that the average monthly cost per patient  with sickle cell disease was $1,389 and that over half of the costs (51.8%)  were directly related to sickle cell disease - and most of that (80.5%) going towards inpatient hospital care. 

Currently, there are 32 orphan drugs designated for treatment some aspect of sickle cell disease. Only hydroxyurea  has orphan drug approval to reduce the frequency of painful crises and the need for blood transfusions in adult patients with sickle cell anemia with recurrent moderate to severe painful crises. That was approved in 1998.  Of the 32 orphan designated drugs, Mast Therapeutics’ drug MST-188 (aka ANX-188 and PP-188) appears to be the one out in front with its recently begun phase 3 EPIC (Evaluation of Purified Poloxamer 188 in Children in Crisis) trial. The purpose of that study is to evaluate whether MST-188 can reduce the duration of vaso-occlusive crisis (VOC) in children (8-17 yrs) with sickle cell disease.


At the Annual Sickle Cell Disease Clinical Research Meetings held in August, John Keefer of the John Hopkins University School of Medicine provided the rationale for the phase 3 study. The study will focus on children since a previous phase 3 study by Orringer et al in 2001 who found that while the entire population of persons with sickle cell disease in the study (n=249) did not show statistically significant difference in the length of crisis (MST-188, 132 hrs vs placebo, 140 hrs; P=0.072), a post hoc analysis focused on the children (n=72) did show statistically significant improvement in length of vaso-occlusive crisis (MST-188, 127 hrs vs placebo 149 hrs; P=0.01).

In the Randomized, double-blind, placebo-controlled, multi-center EPIC trial that has just begun, the treatment arms are MST-188 (100 mg/kg i.v. over 1 hour, followed  by 30 mg/kg/hr i.v. for 48 hours) vs Placebo (½ normal saline i.v. over 49 hours). The study population is pediatric patients limited to those with phenotype to Hb SS and S-beta null thalassemia to provide a homogenous study population. The primary endpoint is duration of crisis resolution defined as the period from time of randomization to last dose of parenteral opioid.

According to clinicaltrials.gov, the expected completion date of the trial is not until Dec 2015.


Keefer JR, Benjamin L, Emanuele M, Padgett C, Betticaden S, Casella JF. EPIC (Evaluation of Purified Poloxamer 188 in Children in Crisis):  An Ongoing Pivotal Phase 3 Study in Patients with Sickle Cell Disease. Presented at the Annual Sickle Cell Disease Clinical Research Meetings August 21, 2013.  Available at http://www.masttherapeutics.com/wp-content/uploads/2013/04/EPIC-An-Ongoing-Pivotal-Phase-3-Study-in-Patients-with-Sickle-Cell-Disease-Aug-21-2013.pdf

Orringer EP, Casella JF, Ataga KI et al. Purified Poloxamer 188 for treatment of acute vaso-occlusive crisis of sickle cell disease. JAMA 2001;286(17):2099-2106. doi:10.1001/jama.286.17.2099

Sickle cell image courtesy of National Heart, Lung, and Blood Institute.


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