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Addressing Sickle Cell Disease: A Strategic Plan and Blueprint for Action (2020)

Chapter: Appendix I: Select Treatments Currently Under Development for Sickle Cell Disease

« Previous: Appendix H: Health Resources and Services Administration Sickle Cell Disease Programs
Suggested Citation:"Appendix I: Select Treatments Currently Under Development for Sickle Cell Disease." National Academies of Sciences, Engineering, and Medicine. 2020. Addressing Sickle Cell Disease: A Strategic Plan and Blueprint for Action. Washington, DC: The National Academies Press. doi: 10.17226/25632.
×
Suggested Citation:"Appendix I: Select Treatments Currently Under Development for Sickle Cell Disease." National Academies of Sciences, Engineering, and Medicine. 2020. Addressing Sickle Cell Disease: A Strategic Plan and Blueprint for Action. Washington, DC: The National Academies Press. doi: 10.17226/25632.
×
Type Name Developer/Sponsor Research Status (as of December 2019) Mechanism Source
Anti-sickling agents IMR-687 Imara Inc.
  • Phase 2a clinical trial—final data collection date for primary outcome measures is estimated for July 2020.
  • Granted U.S. Orphan Drug Designation, U.S. Rare Pediatric Designation, and Fast Track Designation as of June 2019.
IMR-687 is a selective inhibitor of phosphodiesterase-9 in blood cells. It has the potential to help patients with SCD by reducing red blood cell sickling and red blood cell lysis, reducing white blood cell adhesions, and thus ultimately reducing vaso-occlusive crisis and hospitalizations. https://clinicaltrials.gov/ct2/show/record/NCT03401112?term=IMR-687&rank=1
Sanguinate Prolong Pharmaceuticals
  • Phase 2 clinical trial—final data collection date for primary outcome measures was in December 2017.
  • Granted Orphan Drug Designation.
Sanguinate is a carbon monoxide releasing molecule and oxygen transfer agent under clinical development for the treatment of sickle cell anemia and comorbidities. https://clinicaltrials.gov/ct2/show/NCT02411708
Anti-adhesion agents Rivipansel (GMI1070) Pfizer Inc.
  • Phase 3 clinical trial (RESET)—final data collection date for outcome measures was in June 2019.
  • Granted Orphan Drug status and Fast Track status.
Rivipansel is a glycomimetic drug candidate that acts as a pan-selectin antagonist, meaning it binds to all three members of the selectin family: E-, P- and L-selectin. Rivipansel could reduce cell adhesion, activation, and inflammation that are believed to contribute to reduced blood flow through the microvasculature during vaso-occlusive crisis. http://glycomimetics.com/pipeline/programs/rivipansel-gmi-1070

https://www.clinicaltrials.gov/ct2/show/record/NCT02187003?term=rivipansel&rank=5
Suggested Citation:"Appendix I: Select Treatments Currently Under Development for Sickle Cell Disease." National Academies of Sciences, Engineering, and Medicine. 2020. Addressing Sickle Cell Disease: A Strategic Plan and Blueprint for Action. Washington, DC: The National Academies Press. doi: 10.17226/25632.
×
Sevuparin Modus Therapeutics
  • Phase 2 clinical trial—final data collection date for primary outcome measures was in May 2019. It failed to show a meaningful benefit in the total study population.
  • Modus is considering its options for further development of Sevuparin.
Sevuparin, a novel polysaccharide drug with anti-adhesive, anti-aggregate and anti-inflam matory effects, interacts with multiple targets during a vaso-occlusive crisis. These interactions cause the release of blood components bound to each other and bound to the endothelial wall, preventing further occlusions from occurring. https://www.clinicaltrials.gov/ct2/show/record/NCT02515838
Gamunex (intravenous gammaglobulin) Albert Einstein College of Medicine
  • Phase I/II clinical trial—estimated final data collection date for primary outcome measures is in September 2022.
Intravenous immunoglobulin reduces neutrophil adhesion to post capillary venular endothelium and adherent neutrophil interactions with circulating red blood cells, thus increasing microcirculatory blood flow and survival. https://clinicaltrials.gov/ct2/show/NCT01757418
Inclacumab Global Blood Therapeutics
  • Manufacturing under way.
Inclacumab is a novel, fully human monoclonal antibody designed to bind to and selectively inhibit P-selectin, an adhesion molecule found on endothelial cells and platelets that contributes to the cell–cell interactions that are involved in the pathogenesis of vasoocclusive crisis. https://www.gbt.com/programs/scd/inclacumab

continued

Suggested Citation:"Appendix I: Select Treatments Currently Under Development for Sickle Cell Disease." National Academies of Sciences, Engineering, and Medicine. 2020. Addressing Sickle Cell Disease: A Strategic Plan and Blueprint for Action. Washington, DC: The National Academies Press. doi: 10.17226/25632.
×
Type Name Developer/Sponsor Research Status (as of December 2019) Mechanism Source
Antioxidant agents N-acetylcysteine Bloodworks Northwest
  • Pilot study—final data collection date for primary outcome measures was in December 2018.
N-acetylcysteine can modulate SCD by cleaving hyperactive von Willebrand factor, a vascular adhesion protein. https://clinicaltrials.gov/ct2/show/NCT01800526?term=NCT01800526&rank=1
Anti-inflammatory agents Regadenoson GE Healthcare
  • Clinical trial to study the drug’s effect on blood flow—estimated final data collection date for primary outcome measures is in January 2022.
Regadenoson is an A2A adenosine receptor agonist that is a coronary vasodilator commonly used in pharmacologic stress testing. https://clinicaltrials.gov/ct2/show/record/NCT01566890?term=Regadenoson&cond=sickle&rank=3
Anticoagulant and Antiplatelet agents Ticagrelor AstraZeneca
  • Phase 3 clinical trial (HESTIA3)—estimated final data collection date for primary outcome measures is in October 2020.
Ticagrelor is an orally administered, direct-acting, reversibly binding P2Y12 receptor antagonist that inhibits adenosine diphosphate-induced platelet aggregation and inhibits cellular uptake of adenosine by inhibiting the equilibrative nucleoside transporter. https://clinicaltrials.gov/ct2/show/NCT03615924?term=Ticagrelor&cond=sickle+cell+anemia&rank=3
Rivaroxaban University of North Carolina at Chapel Hill
  • Clinical trial to study the drug’s effect on the pathology of SCD—final data collection date for outcome measures was in December 2018.
Inhibition of factor Xa with rivaroxaban will reduce inflammation, coagulation, and endothelial cell activation, and improve microvascular blood flow in patients with SCD during the non-crisis, steady state. https://clinicaltrials.gov/ct2/show/NCT02072668?term=Rivaroxaban&cond=sickle+cell&rank=1
Suggested Citation:"Appendix I: Select Treatments Currently Under Development for Sickle Cell Disease." National Academies of Sciences, Engineering, and Medicine. 2020. Addressing Sickle Cell Disease: A Strategic Plan and Blueprint for Action. Washington, DC: The National Academies Press. doi: 10.17226/25632.
×
Nitric oxide L-Arginine Emory University
  • Phase 2 clinical trials—estimated final data collection date for primary outcome measures is in August 2020.
Low nitric oxide bioavailability contributes to vasculopathy in SCD. L-Arginine is the obligate substrate for nitric oxide production. https://clinicaltrials.gov/ct2/show/NCT02536170?term=Phase+2+Randomized+Control+Trial+of+Arginine+Therapy+for+Pediatric+Sickle+Cell+Disease+Pain&rank=1
Riociguat University of Pittsburgh
  • Phase II clinical trials—estimated final data collection date for primary outcome measures is in December 2020.
Riociguat-mediated activation of guanylate cyclase increases the availability of cGMP in the blood vessels within the lungs, which improves blood vessel function and reduces symptoms of SCD. https://clinicaltrials.gov/ct2/show/NCT02633397
Gene therapy NCT ID: NCT03282656 Boston Children’s Hospital
  • Open-label, non-randomized, single center, pilot and feasibility, single arm cohort study of seven patients—estimated final data collection date for primary outcome measures is in February 2020.
The sickle cell gene therapy clinical trial will involve a single infusion of autologous bone marrow-derived CD34+ hematopoietic stem cells transduced with a lentiviral vector containing a short-hairpin RNA targeting BCL11A. This gene therapy technology, developed at Boston Children’s Hospital, turns down the expression of the BCL11A protein that normally shuts off production of fetal hemoglobin shortly after birth and represses the expression into childhood and adulthood. https://clinicaltrials.gov/ct2/show/NCT03282656

continued

Suggested Citation:"Appendix I: Select Treatments Currently Under Development for Sickle Cell Disease." National Academies of Sciences, Engineering, and Medicine. 2020. Addressing Sickle Cell Disease: A Strategic Plan and Blueprint for Action. Washington, DC: The National Academies Press. doi: 10.17226/25632.
×
Type Name Developer/Sponsor Research Status (as of December 2019) Mechanism Source
BIVV003 Bioverativ Inc.
  • Phase I/IIa clinical trial (PRECIZN-1)—estimated final data collection date for primary outcome measures is September 2022.
  • The U.S. Food and Drug Administration accepted an investigational new drug application submitted in May 2018.
BIVV003 is a non-viral approach that utilizes zinc finger nuclease gene-editing technology to gene edit a patient’s own hematopoietic stem cells. The treatment suppresses sickle hemoglobin production while reactivating the production of fetal hemoglobin to levels that may protect patients against disease progression. https://clinicaltrials.gov/ct2/show/record/NCT03653247
CTX001 CRISPR Therapeutics and Vertex Pharmaceuticals Inc.
  • Phase I/II clinical trial—estimated final data collection date for primary outcome measures is February 2021.
  • Granted Fast Track Designation in January 2019.
An ex vivo gene-edited cell therapy uses a new technology called CRISPR (clustered regularly interspaced short palindromic repeats) to replace stem cells with those engineered to produce high levels of fetal hemoglobin in red blood cells, replacing the damaged hemoglobin. https://clinicaltrials.gov/ct2/show/NCT03745287
LentiGlobin (BB305) bluebird bio, Inc.
  • Phase I/II clinical trial—estimated final data collection date for primary outcome measures is February 2022.
  • Granted Breakthrough Therapy designation in February 2015.
LentiGlobin BB305 Drug Product aims to treat beta-thalassemia major and severe SCD by inserting a functional human beta-globin gene into the patient’s own hematopoietic stem cells ex vivo and then returning those modified cells to the patient through an autologous stem cell transplantation. https://clinicaltrials.gov/ct2/show/record/NCT02140554
Suggested Citation:"Appendix I: Select Treatments Currently Under Development for Sickle Cell Disease." National Academies of Sciences, Engineering, and Medicine. 2020. Addressing Sickle Cell Disease: A Strategic Plan and Blueprint for Action. Washington, DC: The National Academies Press. doi: 10.17226/25632.
×
Transplant Bone marrow transplant from half-matched related donors Emory University
  • The estimated study completion date is in December 2020.
Participants will receive a bone marrow infusion from a human leukocyte antigen (HLA) half-matched donor through a central venous catheter. https://clinicaltrials.gov/ct2/show/NCT02757885?term=supplement&cond=sickle+cell&cntry=US&draw=2&rank=17
Pre-transplant Immunosuppressive Therapy for Haploidentical Transplants City of Hope Medical Center
  • Pilot study—estimated final data collection date for primary outcome measures is February 2023.
Patients will receive a haploidentical hematopoietic stem cell transplant and graft-versus-host-disease prevention with or without pre-transplant immunosuppressive therapy. https://clinicaltrials.gov/ct2/show/NCT03279094
Nonmyeloablative Haploidentical Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation National Heart, Lung, and Blood Institute
  • The estimated final data collection date for primary outcome measures is September 2025.
Patients will receive a nonmyeloablative allogeneic peripheral blood stem cell transplant with allogeneic peripheral blood stem cells from a haploidentical donor using a novel immunosuppressive regimen. https://clinicaltrials.gov/ct2/show/NCT03077542
Mixed Chimerism in Sickle Cell Disease Patients With COH-MC-17 City of Hope Medical Center, California Institute for Regenerative Medicine
  • Pilot study—estimated final data collection date for primary outcome measures is December 2022.
Participants will receive COH-MC-17: a 21-day nonmyeloablative conditioning regimen (cyclophosphamide, pentostatin, and rabbit anti-thymocyte globulin), followed by CD4+ T-cell-depleted Haploidentical Hematopoietic Transplant. https://clinicaltrials.gov/ct2/show/NCT03249831

continued

Suggested Citation:"Appendix I: Select Treatments Currently Under Development for Sickle Cell Disease." National Academies of Sciences, Engineering, and Medicine. 2020. Addressing Sickle Cell Disease: A Strategic Plan and Blueprint for Action. Washington, DC: The National Academies Press. doi: 10.17226/25632.
×
Type Name Developer/Sponsor Research Status (as of December 2019) Mechanism Source
Reduced Intensity Conditioning for Haploidentical Bone Marrow Transplantation Medical College of Wisconsin
  • Phase II clinical trial—estimated final data collection date for primary outcome measures is December 2023.
A conditioning regimen with Hydroxyurea, rabbit-ATG, Thiotepa, Fludarabine, Cyclophosphamide, Total Body Irradiation, and Mesna will be administered prior to Haploidentical Bone Marrow Transplantation in Eligible patients with a first degree HLA-haploidentical donor. https://clinicaltrials.gov/ct2/show/NCT03263559
Familial Haploidentical T-Cell Depleted Transplantation New York Medical College
  • The estimated study completion is in December 2022.
The study investigates host myeloimmunosuppressive conditioning followed by familial haploidentical T-cell depleted allogeneic stem cell transplantation in patients with high risk SCD. https://clinicaltrials.gov/ct2/show/NCT01461837
T-Cell Depleted, Alternative Donor Transplantation Children’s Hospital of Pittsburgh
  • The estimated final data collection date for primary outcome measures is August 2023.
This study will evaluate the effect of mismatched unrelated volunteer donor and/or haploidentical related donor stem cell transplant on patients with SCD. https://clinicaltrials.gov/ct2/show/NCT03653338
Suggested Citation:"Appendix I: Select Treatments Currently Under Development for Sickle Cell Disease." National Academies of Sciences, Engineering, and Medicine. 2020. Addressing Sickle Cell Disease: A Strategic Plan and Blueprint for Action. Washington, DC: The National Academies Press. doi: 10.17226/25632.
×
Supplement Vitamin D3 Columbia University
  • Phase II clinical trial—the estimated study completion date is December 2019.
Vitamin D helps the immune system to fight infection and to control inflammation and could potentially help prevent respiratory complications in patients with SCD. https://clinicaltrials.gov/ct2/show/NCT01443728?term=vitamin+d3&cond=sickle+cell&rank=3
Altemia (SC411) Micelle BioPharma
  • Phase IIa clinical trial—the estimated study completion date is January 2022.
  • Phase III clinical trial (ASCENT)-the estimated study completion date is December 2020.
  • Granted Orphan Drug designation to the drug back in 2015.
Altemia consists of a complex proprietary mixture of various fatty acids, primarily in the form of Ethyl Cervonate™ (Micelle’s proprietary blend of docosahexaenoic acid and other omega-3 fatty acids), and surface active agents formulated using ALT® specifically to address the treatment of SCD. The specific lipids contained in Altemia may restore balance and fluidity to red blood cells and other cells impacted by the disease. Altemia might treat SCD by decreasing blood cell adhesion, chronic inflammation and red blood cell hemolysis, the factors that lead to reduction in pain episodes, vasoocclusive crises, and organ damage. https://micellebiopharma.com/sickle-cell-disease-altemia

https://clinicaltrials.gov/ct2/show/NCT02973360

https://clinicaltrials.gov/ct2/show/record/NCT02604368

NOTES: There are also psychosocial behavioral interventions and holistic approaches to treat sickle cell disease (see Chapter 4) and additional clinical trials on transplants. This table reflects updates through December 2019. SCD = sickle cell disease.

Suggested Citation:"Appendix I: Select Treatments Currently Under Development for Sickle Cell Disease." National Academies of Sciences, Engineering, and Medicine. 2020. Addressing Sickle Cell Disease: A Strategic Plan and Blueprint for Action. Washington, DC: The National Academies Press. doi: 10.17226/25632.
×

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Suggested Citation:"Appendix I: Select Treatments Currently Under Development for Sickle Cell Disease." National Academies of Sciences, Engineering, and Medicine. 2020. Addressing Sickle Cell Disease: A Strategic Plan and Blueprint for Action. Washington, DC: The National Academies Press. doi: 10.17226/25632.
×
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Suggested Citation:"Appendix I: Select Treatments Currently Under Development for Sickle Cell Disease." National Academies of Sciences, Engineering, and Medicine. 2020. Addressing Sickle Cell Disease: A Strategic Plan and Blueprint for Action. Washington, DC: The National Academies Press. doi: 10.17226/25632.
×
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Suggested Citation:"Appendix I: Select Treatments Currently Under Development for Sickle Cell Disease." National Academies of Sciences, Engineering, and Medicine. 2020. Addressing Sickle Cell Disease: A Strategic Plan and Blueprint for Action. Washington, DC: The National Academies Press. doi: 10.17226/25632.
×
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Suggested Citation:"Appendix I: Select Treatments Currently Under Development for Sickle Cell Disease." National Academies of Sciences, Engineering, and Medicine. 2020. Addressing Sickle Cell Disease: A Strategic Plan and Blueprint for Action. Washington, DC: The National Academies Press. doi: 10.17226/25632.
×
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Suggested Citation:"Appendix I: Select Treatments Currently Under Development for Sickle Cell Disease." National Academies of Sciences, Engineering, and Medicine. 2020. Addressing Sickle Cell Disease: A Strategic Plan and Blueprint for Action. Washington, DC: The National Academies Press. doi: 10.17226/25632.
×
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Suggested Citation:"Appendix I: Select Treatments Currently Under Development for Sickle Cell Disease." National Academies of Sciences, Engineering, and Medicine. 2020. Addressing Sickle Cell Disease: A Strategic Plan and Blueprint for Action. Washington, DC: The National Academies Press. doi: 10.17226/25632.
×
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Suggested Citation:"Appendix I: Select Treatments Currently Under Development for Sickle Cell Disease." National Academies of Sciences, Engineering, and Medicine. 2020. Addressing Sickle Cell Disease: A Strategic Plan and Blueprint for Action. Washington, DC: The National Academies Press. doi: 10.17226/25632.
×
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Suggested Citation:"Appendix I: Select Treatments Currently Under Development for Sickle Cell Disease." National Academies of Sciences, Engineering, and Medicine. 2020. Addressing Sickle Cell Disease: A Strategic Plan and Blueprint for Action. Washington, DC: The National Academies Press. doi: 10.17226/25632.
×
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Suggested Citation:"Appendix I: Select Treatments Currently Under Development for Sickle Cell Disease." National Academies of Sciences, Engineering, and Medicine. 2020. Addressing Sickle Cell Disease: A Strategic Plan and Blueprint for Action. Washington, DC: The National Academies Press. doi: 10.17226/25632.
×
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Suggested Citation:"Appendix I: Select Treatments Currently Under Development for Sickle Cell Disease." National Academies of Sciences, Engineering, and Medicine. 2020. Addressing Sickle Cell Disease: A Strategic Plan and Blueprint for Action. Washington, DC: The National Academies Press. doi: 10.17226/25632.
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Sickle cell disease (SCD) is a genetic condition that affects approximately 100,000 people in the United States and millions more globally. Individuals with SCD endure the psychological and physiological toll of repetitive pain as well as side effects from the pain treatments they undergo. Some adults with SCD report reluctance to use health care services, unless as a last resort, due to the racism and discrimination they face in the health care system. Additionally, many aspects of SCD are inadequately studied, understood, and addressed.

Addressing Sickle Cell Disease examines the epidemiology, health outcomes, genetic implications, and societal factors associated with SCD and sickle cell trait (SCT). This report explores the current guidelines and best practices for the care of patients with SCD and recommends priorities for programs, policies, and research. It also discusses limitations and opportunities for developing national SCD patient registries and surveillance systems, barriers in the healthcare sector associated with SCD and SCT, and the role of patient advocacy and community engagement groups.

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