The ASPHO Advocacy Brief
Welcome to the Advocacy Brief, a quarterly offering from the American Society of Pediatric Hematology/Oncology. The goal of this e-newsletter is to inform members about legislative and regulatory issues impacting the profession of pediatric hematology/oncology and the patients we serve.
Sickle Cell Awareness Month
September is Sickle Cell Awareness Month. September’s Advocacy Brief will bring a special focus to sickle cell disease and ASPHO’s efforts to advocate for sickle cell patients.
As sickle cell disease is one of the most common serious conditions identified via newborn screening in the United States, all pediatricians should be familiar with sickle cell disease and aspects of its management. Feel free to share this list with practitioners in your community.
- Penicillin prophylaxis: Start all newborns with sickle cell disease (newborn screen FS, FSA, or FSC) on penicillin 125 mg BID (dose increases to 250 mg BID at age 3 years). Encourage adherence and provide refills if necessary. Hematologists usually advise that most children can safely stop penicillin after age 5 years. A recent study using Medicaid claims data from five states unfortunately found that only 18% of children under age 5 years with sickle cell disease received ≥300 days of prophylactic antibiotics.1
- Fever: Always treat fever as an emergency in a child with sickle cell disease. All children with sickle cell disease with fever require an urgent medical evaluation that typically includes: CBC and reticulocyte count, blood culture, and an IV/IM antibiotic (usually ceftriaxone). Make sure all families know that they should not just monitor a child with fever at home.
- Pneumococcal immunizations: Children with sickle cell disease are at increased risk for pneumococcal sepsis due to functional asplenia. Immunize all children against pneumococcus with both the conjugate (Prevnar) and polysaccharide (Pneumovax) pneumococcal vaccines. If a child received Prevnar-7 as an infant, give a Prevnar-13 booster.
- TCD Screen for Stroke: Children with genotypes hemoglobin SS or Sβ0 thalassemia should receive an annual transcranial Doppler (TCD) ultrasound to identify children at increased risk for stroke. Help make sure these children get their TCD every year from age 2 to 16 years. Sadly many at-risk children do not receive an annual TCD.2,3
- Hydroxyurea: Hydroxyurea is a safe, well tolerated disease modifying medication for sickle cell disease (in particular for hemoglobin SS and Sβ0 thalassemia). If a child is not on hydroxyurea, make sure the family has talked to their hematologist about this important medication. If a child is on hydroxyurea, encourage taking it daily. You can monitor adherence by trending the mean cell volume (MCV) which increases with hydroxyurea treatment.
- Influenza: Immunize children with sickle cell disease against influenza every year! Influenza infection can trigger severe complications of sickle cell disease like acute chest syndrome.
- Sickler: Refrain from using the term “sickler.” Some people with sickle cell disease find this language offensive. Its use among ED providers has also been associated with negative attitudes toward people with sickle cell disease.4 Instead, describe a patient by their genotype as this provides important information.
- Genetic counseling: Make sure to educate families of children with sickle cell trait (newborn screen FAS) about the genetic inheritance of sickle cell disease. This is potentially important information for both the parents (who may both have trait and be at risk of having a child with sickle cell disease) and the child to make informed reproductive decisions.
- No ice: While many common musculoskeletal injuries are typically treated with ice, do not recommend the application of ice for children with sickle cell disease. Ice can trigger red cell sickling that may lead to sickle pain.
- Bedwetting: Nocturnal enuresis is common in children with sickle cell disease. Children with sickle cell disease have hyposthenuria (dilute urine) because sickle cell impairs the ability of the kidneys to concentrate urine. Offer support to families dealing with this problem.
The opportunities for patients with sickle cell disease to participate in clinical research have improved significantly in the past few decades. Current research is exploring ways to reduce the risks of serious complications, including stroke, hypertension, respiratory problems, and vulnerability to overwhelming bacterial infections. It is imperative that we, as physicians, encourage patients to participate in research studies that will hopefully lead to advancements in diagnosis and treatment. There are 100 active research studies in SCD registered on www.clinicaltrials.gov as of August 22, 2018; these studies are being conducted all over the United States.
Development of new drugs in sickle cell disease (SCD) as well as investigation of drugs previously used in other settings have targeted cell adhesion, inflammatory pathways, upregulation of hemoglobin F, hemoglobin polymerization and sickling, coagulation, and platelet activation. Although these efforts have not yielded many drugs ready for FDA approval, several early studies have been extremely encouraging. In addition, the marked increase in clinical pharmaceutical research addressing SCD and the new and old drugs in the pipeline make it reasonable to expect that we will soon have new treatments for SCD (excerpt from Blood 2016 127:810-819).
There is one new drug that has been recently FDA approved for use in pediatric and adult patients with SCD. In July 2017, Endari (L-glutamine oral powder) was approved for patients age five years and older with SCD to reduce severe complications associated with the blood disorder. This is the first treatment approved for patients with SCD in almost 20 years! The safety and efficacy of Endari were studied in a randomized trial of patients ages 5 to 58 years old who had two or more painful crises within the 12 months prior to enrollment in the trial. Patients were assigned randomly to treatment with Endari or placebo, and the effect of treatment was evaluated over 48 weeks. Patients who were treated with Endari experienced fewer hospital visits for pain treated with a parenterally administered narcotic or ketorolac (sickle cell crises), on average, compared to patients who received a placebo (median 3 vs. median 4), fewer hospitalizations for sickle cell pain (median 2 vs. median 3), and fewer days in the hospital (median 6.5 days vs. median 11 days). Patients who received Endari also had fewer occurrences of acute chest syndrome compared with patients who received a placebo (8.6% vs. 23.1%). Common side effects of Endari include constipation, nausea, headache, abdominal pain, cough, pain in the extremities, back pain and chest pain. Endari received Orphan Drug designation for this use, which provides incentives to assist and encourage the development of drugs for rare diseases. In addition, development of this drug was in part supported by the FDA Orphan Products Grants Program, which provides grants for clinical studies on safety and/or effectiveness of products for use in rare diseases or conditions. The study was recently published in NEJM (Niihara, Y, et al. A Phase 3 Trial of L-Glutamine in Sickle Cell Disease. NEJM 19 July 2018).
An additional drug currently being studied is Voxelotor (previously called GBT440), an oral, once-daily therapy for patients with SCD. Voxelotor works by increasing hemoglobin's affinity for oxygen. Since oxygenated sickle hemoglobin does not polymerize, Global Blood Therapeutics (GBT) – the clinical-stage biopharmaceutical company developing the drug - believes voxelotor blocks polymerization and the resultant sickling of red blood cells. With the potential to improve hemolytic anemia and oxygen delivery, GBT believes that voxelotor may potentially modify the course of SCD. In recognition of the critical need for new SCD treatments, the FDA granted voxelotor Breakthrough Therapy, Fast Track, Orphan Drug and Rare Pediatric Disease designations for the treatment of patients with SCD. GBT is currently evaluating Voxelotor in the HOPE (Hemoglobin Oxygen Affinity Modulation to Inhibit HbS PolymErization) Study, a Phase 3 clinical study in patients age 12 and older with SCD. In June of this year, GBT announced positive top-line data from Part A of the Phase 3 HOPE study. The primary endpoint was achieved with 58% of patients on Voxelotor exceeding a 1g/dL increase in hemoglobin at Week 12 of therapy compared to 9% of placebo (p<0.0001). The company met with the FDA at the end of June and is in discussions on potential accelerated approval based on the drug’s efficacy as assessed by the primary endpoint. In addition, there were numerically fewer vaso-occlusive crises (VOC) in each Voxelotor arm vs placebo.
- Progress has been made but research breakthroughs have been few
- It is important that these patients be managed by a team knowledgeable in treatment of sickle cell disease. Lack of such teams results in lack of access to quality care.
- Ensure support for passage of the Sickle Cell Disease Research, Surveillance, Prevention and Treatment Act, which would increase funding for research and treatment of these patients
In July 2018, ASPHO joined the American Society of Hematology in sending a letter to Senators Lamar Alexander and Patty Murry, the Chair and Rank Member, respectively, of the Senate Health, Education, Labor, and Pensions (HELP) Committee, asking them to support S. 2465, the Sickle Cell Disease Research, Surveillance, Prevention and Treatment Act of 2018 and pass the bill out of committee and to a full Senate vote. S. 2465 would authorize a national surveillance program, which would help with a greater understanding of how many Americans are affected with sickle cell, where they live, where they receive care, and whether they have access to care. The bill also reauthorizes the existing Health Resources and Services Administration’s SCD Treatment Demonstration Program, which is important to improving patient access to the highest quality of care. The Demonstration Program continues to yield valuable results, increasing the number of SCD providers’ knowledgeable about the most effective treatments for the disease. The Senate bill passed out of the HELP Committee and is awaiting a full Senate vote. If you want to help, contact your Senators and ask them to pass this bill.
The American Society of Hematology (ASH) has opened for public comment draft clinical practice guidelines on sickle cell disease-related transfusion support. More information and supporting materials may be found here. The deadline to comment is Monday, October 1, 2018.
The Senate is beginning consideration of the Labor/HHS Appropriations bill that funds national health programs, including the NIH. We wanted to give you a quick update on the status of funding for the Childhood Cancer STAR Act. We need your help to reach out to members of the House Appropriations Committee Subcommittee on Labor, Health and Human Services, Education, and Related Agencies (House LHHS Subcommittee) and ask them to fully fund the Childhood Cancer Survivorship, Treatment, Access, and Research Act of 2018 (Childhood Cancer STAR Act). The Childhood Cancer STAR Act is the most comprehensive funding bill for childhood cancer research. This bill expands opportunities for cancer research, enhances the ability to track childhood cancers, and enhances the quality of life for childhood cancer survivors. ASPHO spent many years advocating for the bill and it was finally signed into law on June 5, 2018.
However, the bill still needs to be funded. How can you help? We need constituents of the members listed here to contact their Representative on the House Labor/HHS Appropriations Subcommittee and ask them to fully fund the Childhood Cancer STAR Act.