Appendix I
Select Treatments Currently Under Development for Sickle Cell Disease
The table begins on the following page.
Type | Name | Developer/Sponsor | Research Status (as of December 2019) | Mechanism | Source |
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Anti-sickling agents | IMR-687 | Imara Inc. |
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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 |
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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. |
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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 |
Sevuparin | Modus Therapeutics |
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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 |
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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 |
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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
Type | Name | Developer/Sponsor | Research Status (as of December 2019) | Mechanism | Source |
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Antioxidant agents | N-acetylcysteine | Bloodworks Northwest |
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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 |
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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 |
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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 |
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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 |
Nitric oxide | L-Arginine | Emory University |
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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 |
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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 |
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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
Type | Name | Developer/Sponsor | Research Status (as of December 2019) | Mechanism | Source |
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BIVV003 | Bioverativ Inc. |
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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. |
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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. |
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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 |
Transplant | Bone marrow transplant from half-matched related donors | Emory University |
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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 |
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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 |
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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 |
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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
Type | Name | Developer/Sponsor | Research Status (as of December 2019) | Mechanism | Source |
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Reduced Intensity Conditioning for Haploidentical Bone Marrow Transplantation | Medical College of Wisconsin |
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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 |
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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 |
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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 |
Supplement | Vitamin D3 | Columbia University |
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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 |
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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.
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