(San Diego, December 3, 2016) — Sickle cell disease (SCD) is an inherited chronic disorder characterized by rigid, sickle-shaped red blood cells that get stuck in veins and block blood flow, which can cause severe pain, stroke, organ failure, and complications leading to death. Each year, approximately 300,000 people around the world are born with SCD, and most of them lack access to comprehensive care or effective treatment options. In fact, the only established long-term therapy for SCD, a pill called hydroxyurea approved more than a decade ago to treat complications stemming from the disease, is widely underused in resource-poor countries.
There is an enormous need to improve the quality of life for people with SCD and decrease global mortality rates. Three studies presented today during the 58th American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego report on encouraging advances for SCD treatment that carry global public health implications.
“Taken together, these studies are helping to unlock new therapeutic approaches, improve access to comprehensive care, and find global solutions, which echo key priority areas set forth by ASH and other leading organizations in the new State of Sickle Cell Disease: 2016 Report to address unmet medical needs for people with SCD,” said moderator Kim Smith-Whitley, MD, clinical director, Division of Hematology and director of the Comprehensive Sickle Cell Center at The Children's Hospital of Philadelphia.
“They also reinforce the need to focus on drugs and interventions that improve the ability of people living with SCD to achieve what they want to achieve, whether that’s graduating from high school or college, being able to parent, or commit to a job that they can go to every day reliably,” she added. “We are closer than ever to improving quality of life for people with SCD, but we have to keep pushing forward and make sure that we are patient-centric in the research we pursue.”
This press conference will take place on Saturday, December 3 at 10:00 a.m. PST in Room 22 of the San Diego Convention Center.
Investigational Drug Reduces Pain Crises by Nearly Half in Patients with Sickle Cell Disease
SUSTAIN: A Multicenter, Randomized, Placebo-Controlled, Double-Blind, 12-Month Study to Assess Safety and Efficacy of SelG1 with or without Hydroxyurea Therapy in Sickle Cell Disease Patients with Sickle Cell-Related Pain Crises 
In a multicenter clinical trial, the novel targeted drug SelG1 reduced the frequency of pain crises by nearly half compared with a placebo in adolescents and adults with SCD. These results suggest that SelG1 may offer another treatment option for patients with SCD who cannot tolerate or are reluctant to take hydroxyurea — currently the only U.S. Food and Drug Administration (FDA)–approved treatment for complications of SCD — or those for whom hydroxyurea is ineffective.
While normal red blood cells are flexible and can easily move through blood vessels, sickled cells are prone to sticking together and to other blood cells and to the lining of blood vessels, which obstructs blood flow, interrupts oxygen delivery to the body’s tissues, and causes severe pain. These painful episodes occur unpredictably and often require hospitalization. SelG1 is an experimental drug that blocks the action of a protein called P-selectin, which preclinical studies have identified as a prime culprit in the cell stickiness that leads to blood-vessel obstruction.
The SUSTAIN trial involved 198 SCD patients ages 16–65 who had experienced at least two and as many as 10 pain crises during the previous year. Patients were randomly assigned to receive 5 mg/kg or 2.5 mg/kg of SelG1 or a placebo intravenously once a month, after an initial loading dose. Some patients in the trial were also receiving hydroxyurea. After one year, the median annual rate of pain crises was reduced by 47 percent in patients treated with 5 mg/kg of SelG1 compared with those in the placebo group and by 33 percent in patients treated with 2.5 mg/kg of the drug. In addition, the median times to the first and second pain crises were more than 2-fold longer in patients treated with 5 mg/kg of SelG1 compared with placebo.
“Patients who received the highest dose of SelG1 had a significant and clinically meaningful reduction in pain crises,” said lead study author Kenneth I. Ataga, MBBS, of the University of North Carolina at Chapel Hill. “Although some side effects were reported, overall the drug seemed to be very well tolerated. I believe it will make a significant difference in patients’ lives.”
The SUSTAIN trial was not designed to determine whether treatment with SelG1 extends patients’ lives, Dr. Ataga said. Long-term follow-up studies will be needed to establish whether the drug affects survival. Additional studies will also be needed to evaluate the drug in younger children with SCD. SelG1 is not currently approved by the FDA.
Funding for this study was provided by a National Heart, Lung, and Blood Institute Small Business Innovation Research award to Selexys Pharmaceuticals.
Kenneth I. Ataga, MD, University of North Carolina at Chapel Hill, will present this study during the Plenary Scientific Session on Sunday, December 4 at 2:00 p.m. in Hall AB of the San Diego Convention Center. The study will be simultaneously published in the New England Journal of Medicine at the time of the press briefing presentation.
Hydroxyurea is Safe and May Reduce Stroke Risk in African Children with Sickle Cell Anemia
Feasibility Trial for Primary Stroke Prevention in Children with Sickle Cell Anemia in Nigeria (SPIN Trial) 
Results of the first National Institutes of Health–funded study of SCD to be conducted in Africa suggest that a moderate dose of the drug hydroxyurea is safe and may reduce the risk of stroke in children with SCD. These preliminary findings have helped pave the way to a Phase III multicenter randomized trial that is now underway to test which dose of hydroxyurea is superior for stroke prevention in a larger population of African children with SCD.
Children with sickle cell anemia (SCA), the most common form of SCD, have a risk of stroke that is more than 300 times greater than that of healthy children. In high-income countries such as the United States, regular blood-transfusion therapy has dramatically reduced this risk. By contrast, in low-resource countries such as Nigeria — home to nearly half of the 300,000 children worldwide born with SCD each year —blood-transfusion therapy is either unsafe, too costly for most patients and families to afford, or both. This feasibility trial was conducted to determine whether hydroxyurea, an oral drug used for more than 30 years to treat complications of SCA, is acceptable treatment to reduce stroke risk among Nigerian children with SCA and to establish safety-monitoring procedures.
Twenty-five children with SCA ages 5 to 12 who were at high risk for stroke received a once-daily dose of 20 mg/kg of hydroxyurea. They were compared with 210 children in the same age group who had SCA but were not at elevated risk for stroke. After a median of two years of follow-up, no children treated with hydroxyurea therapy developed a stroke when compared to one patient in the comparison group. Furthermore in the treatment group when compared to the comparison group, the hospitalization rate was of 35.1 and 48.0 per 100 patient-years, respectively. One patient in the treatment group had unrecognized progressive renal disease at the time of enrollment, subsequently withdrawn from the study and died. Eight patients in the comparison group died.
“In this feasibility trial, we have shown that a moderate dose of hydroxyurea does not cause adverse effects and may be effective for stroke prevention,” said lead study author Najibah A. Galadanci, MBBS, MPH, of Bayero University in Kano, Nigeria. “These results provide strong preliminary evidence to support the current randomized trial.” Results of that trial, which is comparing two doses of hydroxyurea — 20 mg/kg/day versus 10 mg/kg/day — for stroke prevention in 220 Nigerian children with SCA, are expected in 2021.
Funding for this study was provided by a National Institutes of Health R21 grant (1R21NS08063), Fogarty Center (R25 TW009337), Burroughs Wellcome Foundation, Phillips Family Donation, Aaron Ardoin Foundation for Sickle Cell Anemia, Vanderbilt endowed funds.
Najibah Aliyu Galadanci, MBBS, MPH, Bayero University/Aminu Kano Teaching Hospital, Kano, Nigeria, will present this study during an oral presentation on Saturday, December 3 at 12:15 p.m. in Room 28ABCD of the San Diego Convention Center.
Multidisciplinary Care of Pregnant Women with SCD Saves Lives
Prospective Implementation of MultiDisciplinary Obstetric Team Decreases the Mortality Rate of Pregnant Women with Sickle Cell Disease in Ghana 
Implementing a multidisciplinary care team approach and establishing dedicated wards to care for pregnant women with SCD in Africa significantly reduces maternal and perinatal mortality after just 13 months, according to a study by researchers in Ghana.
“We saw a dramatic drop — close to a 90 percent reduction — in maternal deaths, which is really remarkable, especially in such a short period,” said lead author Eugenia Vicky Naa Kwarley Asare, MBChB, BSc, of the Ghana Institute of Clinical Genetics, Korle-Bu and the KorleBu Teaching Hospital in Accra, Ghana. “Sickle cell disease has acute and chronic complications, and to manage it well, especially in the context of pregnancy and childbirth, you need to have a number of specialists on board, including a hematologist.”
Dr. Asare says the obstetrics clinic at Korle-Bu Teaching Hospital sees approximately 250 pregnant women with SCD each year — up to 12 percent of whom die during pregnancy and after childbirth. In 2015, several efforts were put in place, including the assembly of a multidisciplinary care team with a dedicated hematologist to closely follow these women. Protocols were also put in place that included regular team meetings to discuss complex patients and to prevent and/or rapidly respond to any acute problems to help stem the tide of deaths. In this study, the researchers compared deaths and other outcomes before and after this intervention was put in place.
In the pre-intervention period (16 months), there were a total of 158 pregnancies in women with SCD ranging from 18–43 years of age; 90 were included in the post-intervention period (13 months). Prior to the intervention, pregnant women with SCD received standard care, mostly by their obstetrician, and were admitted to multiple wards throughout the hospital. By contrast, women who received integrated care were evaluated by a multidisciplinary team including obstetricians with expertise in high-risk pregnancy, hematologists, pulmonologists, anesthesiologists, and nurses at enrollment, during all outpatient visits, and as any acute issues arose. They were closely followed until six weeks postpartum. Simple practices were put in place to prevent and manage acute issues including acute chest syndrome, which is a leading cause of death in these pregnant women, and acute pain episodes. The team also began routinely monitoring blood-oxygen saturation levels and performing Doppler ultrasounds and other tests for the fetus. Inpatient care was centralized to two designated wards to facilitate coordinated, rapid activation of medical services.
Analyses showed an 89 percent drop in maternal deaths (9.5% vs. 1.1%) and a 62 percent reduction in perinatal mortality (60.8% vs 23% per 1,000 total births) after a multidisciplinary SCD-obstetric team was activated.
Because there was not the same level of coordinated care and tracking of women prior to the multidisciplinary care teams being put in place, some data were incomplete, limiting comparisons. Still, the researchers will expand their approach to decrease maternal and perinatal mortality in other hospitals in Accra, Ghana. The strategy of including a multidisciplinary team with standard protocols for the care of pregnant women with SCD could have widespread public health benefits for pregnant women with SCD across sub-Saharan Africa and perhaps even in the United States where such clinics are not the norm.
Funding for the study was provided partly by Intramural Funds (Office of Research and Innovation), University of Ghana; Vanderbilt University Medical Center Gift Funds; Doris Duke Charitable Foundation; Burroughs Wellcome Foundation; Phillips Family Donation; Aaron Ardoin Foundation for Sickle Cell Anemia; and endowed chair funds from Vanderbilt University School of Medicine.
Eugenia Vicky Naa Kwarley Asare, MBChB, BSc, Ghana Institute of Clinical Genetics and the Department of Hematology, Korle-Bu Teaching Hospital in Accra, Ghana, will present this study during an oral presentation on Monday, December 5 at 5:00 p.m. in Room 6DE of the San Diego Convention Center.
The study authors and press program moderator will be available for interviews after the press conference or by telephone. Additional press briefings will take place at the meeting on personalized medicine and novel therapies. For the complete annual meeting program and abstracts, visit www.hematology.org/annual-meeting. Follow @ASH_hematology and #ASH16 on Twitter and like ASH on Facebook for the most up-to-date information about the 2016 ASH Annual Meeting.
The American Society of Hematology (ASH) (www.hematology.org) is the world's largest professional society of hematologists dedicated to furthering the understanding, diagnosis, treatment, and prevention of disorders affecting the blood. For more than 50 years, the Society has led the development of hematology as a discipline by promoting research, patient care, education, training, and advocacy in hematology. The Society publishes Blood (www.bloodjournal.org), the most cited peer-reviewed publication in the field, as well as the newly launched, online, open-access journal, Blood Advances.
Richele Keas, FleishmanHillard
Stephen Fitzmaurice, ASH