SAN DIEGO, Dec. 3, 2016 /PRNewswire-USNewswire/ -- 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 [1]
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 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)
[122]
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.1 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
[1017]
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.
1 See
https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-016-0704-2
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