Joint FDA/ASH Led Initiative Highlights Importance of Using Patient Reported Outcomes and Biomarkers in Clinical Trials to Advance SCD Therapies
(WASHINGTON, DC, Dec. 6, 2019) — The American Society of Hematology (ASH) today released the most comprehensive set of recommendations to date aimed at establishing uniformity and global standards for clinical trial endpoints used to evaluate new therapies for sickle cell disease (SCD). The new recommendations – published in two companion papers in the current issue of Blood Advances – are the result of seven expert and patient led panels convened by ASH and the U.S. Food and Drug Administration (FDA) to improve the design of clinical trials for new SCD therapies, including promoting broader use of patient reported outcomes and biomarkers as clinical endpoints.
Sickle cell disease is the most common inherited red blood cell disorder in the United States, and it affects millions of people worldwide. In people living with SCD, the red blood cells, which are normally round, become crescent or sickle-shaped which contributes to the vaso-occlusive crises these patients experience. People with SCD suffer from an array of physical complications, including acute pain crises, joint and organ damage, impaired cognitive function, and a reduced life expectancy. In addition to the immense physical burden they must endure, people with SCD are often stigmatized due to a poor understanding among healthcare professionals and the general public of the life-limiting effects of the disease. Supporting SCD research and access to care efforts for all people living with the disease is a chief priority for ASH.
While the molecular basis of SCD has been well understood for decades, there are currently only four FDA approved treatments for this debilitating condition. Bone marrow transplant is a cure for some individuals with SCD, but it is not an option for everyone. Although two new treatments for SCD have recently been approved, and many others – including potentially curative gene therapies – are in development, medical experts and FDA officials agree there is a need for uniformity around clinical trial endpoints to ensure these new therapies deliver a meaningful benefit from the patient’s perspective. “There are a number of investigational drugs in development that target different manifestations of SCD,” said Julie Panepinto, MD, MSPH, FAAP, Professor of pediatric hematology, Medical College of Wisconsin/Children’s Wisconsin, co-chair of ASH’s Guideline Oversight Committee, and co-chair of the workshop. “However, there are no clear standardized endpoints for evaluating the effect of therapies on clinical outcomes and patient well-being.”
Dr. Panepinto said that amid the burgeoning effort to develop curative SCD therapies, clinical research should incorporate endpoints that are not only measurable, but also relevant and directly beneficial to the patient based on their preferences and experience.
“What’s happening in SCD is really exciting and many of us feel we are on the cusp of identifying multiple disease-modifying therapies,” Dr. Panepinto said. “The field is exploding, so we want to be sure we are measuring relevant endpoints for researchers, clinicians, and patients because that helps us advance the field and get new therapies approved.”
Ann Farrell, MD, Director of the FDA’s Division of Hematology Products and co-chair of the workshop, points out that the scientific understanding and the treatment of SCD have evolved to a point that the endpoints used to evaluate earlier SCD treatments are now inadequate.
“These changes have greatly impacted the discussion the Agency is having with the pharmaceutical industry as new clinical trials are designed,” said Dr. Farrell. “We need endpoints that better reflect the patient experience of their disease in the current healthcare system.”
To address the global burden of SCD, ASH and the FDA convened seven panels of clinicians, investigators, and people with SCD in a two-day workshop to bring uniformity and standards to existing endpoints, identify gaps, and propose development of new endpoints as a focus for future research. Led by Drs. Panepinto and Farrell, the panels conducted extensive literature reviews, assessed available evidence, and used expert judgement to identify which existing endpoints can be incorporated into SCD clinical trials and what additional data are needed. The panels focused on the following areas:
· Patient reported outcomes (PROs) – the panel suggested that future trials should measure the impact in three key domains: crisis and non-crisis pain; affect (including emotional impact, sleep quality and fatigue), and function (social, physical and cognitive),
· Pain (non-PROs) – this panel recommended measuring healthcare utilization, analgesic use, and physical function as a complementary measure to PROs on pain,
· The brain – the panel reviewed and identified diagnostic modalities to assess neurological risk, document stroke, and measure cognition and educational attainment,
· End-organ considerations – the panel stressed the need to use biomarkers and endpoints that capture the progression of renal and cardiopulmonary disease,
· Biomarkers – this panel overlapped with other panels addressing various disease manifestations, highlighting the importance of developing and validating a broader array of biomarkers that can measure response to therapy,
· Measurements of cure – given this is a relatively new area of research, the panel identified the need to develop appropriate biomarkers to evaluate the effect of curative therapies, and to capture and share these data in a central repository to help advance the scientific understanding and broader use of these treatments,
· Care in low-resource settings – this panel noted an opportunity to accelerate clinical trials in regions with a high prevalence of SCD, such as sub-Saharan Africa. They also recommended capturing data on early childhood, peri-operative and pregnancy-related mortality, as well as PROs from children and their caregivers relating to growth and development.
The published recommendations represent the most comprehensive review of science to date in the treatment of SCD and will be a valuable reference for academic researchers seeking funding for scientific studies and pharmaceutical companies looking to identify endpoints for specific clinical trials.
“The papers document the wide-ranging discussions held by researchers, patients, caregivers, international experts, pharmaceutical industry and government to understand where we are in terms of defining clinical trial endpoints for current use and those for future development that will serve patients best,” said Dr. Farrell. She also noted the initiative identified several opportunities to incorporate the patient voice in clinical practice to help better understand how effective current medical treatments are.
The workshop was modeled after an earlier ASH/FDA initiative that focused on leukemia and myeloma, and was generously supported solely by the philanthropic support from numerous individual donors who contributed to the ASH Foundation’s Sickle Cell Disease Initiative Fund and by the Doris Duke Charitable Foundation.
In 2016, ASH launched a multifaceted initiative to address the burden of disease both in the United States and globally. For this initiative, ASH has developed clinical guidelines for SCD management and care, expanded education and training efforts, advocated with policymakers to enhance and expand federal SCD programs, and founded the Sickle Cell Disease Coalition. In addition to these efforts, the ASH Research Collaborative (ASH RC) SCD Clinical Trials Network was developed with the mission to improve outcomes for individuals with SCD by expediting SCD therapy development and facilitating innovation in clinical trial research. It provides the infrastructure for identifying patient cohorts for trials, matching trial sponsors with sites, facilitating recruitment of eligible patients, and ensuring optimally designed trials and an efficient, coordinated approach. Through patient engagement and optimized clinical trial execution, the Clinical Trials Network is helping to bring new and more effective therapies to individuals with SCD.
Papers in Blood Advances:
· End points for sickle cell disease clinical trials: patient-reported outcomes, pain, and the brain
· End points for sickle cell disease clinical trials: renal and cardiopulmonary, cure, and low-resource setting
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 60 years, the Society has led the development of hematology as a discipline by promoting research, patient care, education, training, and advocacy in hematology. ASH publishes Blood (www.bloodjournal.org), the most cited peer-reviewed publication in the field, and Blood Advances (www.bloodadvances.org), an online, peer-reviewed open-access journal. 

Oxbryta™ (voxelotor) tablets Now Approved

On behalf of GBT, we are happy to share that Oxbryta (pronounced ox-brye-ta) is now approved by the U.S. Food and Drug Administration (FDA). Oxbryta is a prescription medicine used for the treatment of sickle cell disease in adults and children 12 years of age and older.1 It is not known if Oxbryta is safe and effective in children below 12 years of age.1
This indication is approved under accelerated approval based on increase in hemoglobin (Hb). Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).2
This approval has been the result of years of collaboration with the community, and we are so grateful for your role in helping GBT get this to patients quickly!
1) Oxbryta is the brand name for voxelotor. This approval represents a historic one, as Oxbryta is the first sickle cell disease drug approved under both the Breakthrough Therapy and Accelerated Approval designations by the FDA.
· Voxelotor is a hemoglobin S (HbS) polymerization inhibitor.2
· Nonclinical studies suggest that voxelotor may inhibit red blood cell (RBC) sickling, improve RBC deformability, and reduce whole blood viscosity.2
· It is a prescription medicine (tablet) taken by mouth once daily, every day.1
2) Oxbryta should not be taken if a patient has had an allergic reaction to voxelotor or any of the ingredients in Oxbryta. Oxbryta can cause side effects including: headache, diarrhea, stomach (abdominal) pain, nausea, tiredness, rash and fever.1
Patient Support: GBT Source Solutions™
As part of GBT’s commitment to supporting access to care for patients, we have launched GBT Source Solutions, a resource center for patients who have been prescribed Oxbryta by their healthcare provider. GBT Source Solutions will provide support by:
· Reviewing insurance coverage options and explaining benefits.
· Coordinating shipment of Oxbryta and explaining Specialty Pharmacy benefits.
· Helping to pay for treatment with financial and co-pay assistance for eligible patients.
· Helping to stay on treatment with a nurse support team. The nurse support team is there to support product adherence, and not to replace a patient’s treatment plan. They do not provide medical advice or case management services.
Your role
Your organization plays a critical role in supporting patients, and we are very thankful for everything you do for people living with SCD. Your collaboration is critical to helping inform patients about Oxbryta and GBT’s patient support services for patients prescribed Oxbryta.
If a patient is interested in learning more about Oxbryta, they should consult their healthcare professional or visit www.Oxbryta.com.
We have attached in this email several resources. You may share these with patients, caregivers, and other members of your community.
… Oxbryta fact sheet
… Oxbryta patient education brochure
… GBT Source Solutions brochure
Please feel free to reach out with any questions. We look forward to continuing our collaboration to help improve the lives of SCD patients and provide hope to our community.
Warmest regards,
Jung
INDICATION AND IMPORTANT SAFETY INFORMATION
INDICATION
What is OXBRYTA?
OXBRYTA is a prescription medicine used for the treatment of sickle cell disease in adults and children 12 years of age and older.
It is not known if OXBRYTA is safe and effective in children below 12 years of age.
This indication is approved under accelerated approval based on increase in hemoglobin (Hb). Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
IMPORTANT SAFETY INFORMATION
Do not take OXBRYTA if you have had an allergic reaction to voxelotor or any of the ingredients in OXBRYTA. See the end of the patient leaflet for a list of the ingredients in OXBRYTA.
If you are receiving exchange transfusions, talk to your healthcare provider about possible difficulties with the interpretation of certain blood tests when taking OXBRYTA.
Before taking OXBRYTA, tell your healthcare provider about all of your medical conditions, including if you:
· have liver problems
· are pregnant or plan to become pregnant. It is not known if OXBRYTA can harm your unborn baby.
· are breastfeeding or plan to breastfeed. It is not known if OXBRYTA can pass into your breastmilk and if it can harm your baby. Do not breastfeed during treatment with OXBRYTA and for at least 2 weeks after the last dose.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Some medicines may affect how OXBRYTA works. OXBRYTA may also affect how other medicines work.
What are the possible side effects of OXBRYTA?
OXBRYTA can cause serious side effects, including:
Serious allergic reactions. Tell your healthcare provider or get emergency medical help right away if you get:
· rash
· hives
· shortness of breath
· swelling of the face
The most common side effects of OXBRYTA include:
· headache
· diarrhea
· stomach (abdominal) pain
· nausea
· tiredness
· rash
· fever
These are not all the possible side effects of OXBRYTA.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
You may also report side effects to Global Blood Therapeutics at 1-833-428-4968 (1-833-GBT-4YOU).
Keep OXBRYTA and all medicines out of the reach of children.
1 Patient Information Leaflet 11 2019
2 USPI 11 2019