Drug discovery
111
drugs
With orphan designations
Overview
Sickle cell disease (SCD) is an inherited hemoglobinopathy characterized by abnormal, sickle-shaped red blood cells that cause vaso-occlusion, chronic hemolytic anemia, and multiorgan damage. Clinical manifestations include acute pain crises, stroke, infections, and progressive organ dysfunction. Management integrates disease-modifying therapies (e.g., hydroxyurea, gene therapies) and supportive care to reduce complications and improve quality of life [1][3][11].
Population
Affects ~100,000 Americans, predominantly non-Hispanic Black individuals (1 in 365 births) and Hispanic Americans (1 in 16,300 births) [2][17].
Global prevalence exceeds 7.7 million, with 80% of cases in sub-Saharan Africa [9][14]. Newborn incidence is rising, projected to reach 400,000 annual births by 2050 [14][15].
Burden
Reduces US life expectancy by >20 years; in low-resource settings, ≤90% mortality before adulthood [4][7][14].
Total mortality burden reached 376,000 deaths globally in 2021, 11× higher than cause-specific estimates [4][9].
Complications drive frequent hospitalizations, with high socioeconomic vulnerability in 67% of US cases [2][10].
Categories: rare genetic diseases, rare hematological diseases, rare transplant-related disorders
Drug Discovery Landscape
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
tebapivat | small molecules | FDA | 2026-02-19 | — | Agios Pharmaceuticals, Inc. |
desidustat | small molecules | FDA | 2026-02-04 | — | Zydus Healthcare (USA), LLC, |
Nangibotide | peptides | EMA | 2025-11-21 | — | Inotrem |
fetal hemoglobin activator cereblon (CRBN) E3 ligase-modulating drug | small molecules | FDA | 2025-06-23 | — | Bristol-Myers Squibb |
(lE, 6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6- heptadiene-3,5-dione) | small molecules | FDA | 2025-06-09 | — | Vascarta Inc. |
autologous CD34+ cell therapy comprised of hematopoietic stem and progenitor cells base edited with one guide RNA and a single messenger RNA encoding an adenine base editor | cell therapies | FDA | 2025-05-30 | — | Beam Therapeutics |
rilzabrutinib | small molecules | FDA | 2025-05-15 | — | Sanofi US Services Inc. |
Mitapivat sulfate | small molecules | EMA | 2024-12-13 | — | Agios Netherlands B.V. |
(8'-hydroxy-6'-oxo-3'-phenyl-6'H-spiro[cyclopentyl-1,5'-indolazine]-7'-carbonyl) glycine | small molecules | FDA | 2024-10-24 | — | KIND Pharmaceuticals LLC |
ex vivo manufactured allogeneic red blood cells derived from hematopoietic progenitor cells | cell therapies | FDA | 2024-10-07 | — | Safi Biotherapeutics, Inc. |
pyrindinyl benzaldehyde | small molecules | FDA | 2024-09-04 | — | Illexcor Therapeutics, LLC |
l-arginine | other | FDA | 2024-05-08 | — | Emory University |
Beta-nicotinamide mononucleotide | small molecules | FDA | 2023-12-14 | — | Nuvamid SA |
a recombinant, humanized single variable domain on a heavy chain (VHH) bispecific antibody that binds with high affinity to human properdin and human serum albumin | antibodies | FDA | 2023-08-21 | — | Alexion Pharmaceuticals, Inc. |
Tarperprumig | antibodies | EMA | 2023-07-25 | — | Alexion Europe |
Nicotinamide mononucleotide | small molecules | EMA | 2023-06-20 | — | LGD |
Autologous CD34+ hematopoietic stem and progenitor cells edited by CRISPR/CAS12a at the HBG1 and HBG2 promoters | cell therapies | FDA | 2023-04-26 | — | Editas Medicine, Inc. |
Epeleuton | small molecules | EMA | 2022-10-11 | — | Afimmune Limited |
2-[(1,3-Benzoxazol-2-yl)amino]-N-[2-(2-hydroxyethoxy)ethyl]-1-methyl-1H-benzimidazole-5- carboxamide monophosphate | small molecules | FDA | 2022-09-01 | — | Astellas Pharma Global Development, Inc. |
15(S)-hydroxy-(5Z,8Z,11Z,13E,17Z)-eicosapentaenoic acid ethyl ester (15(S)-HEPE-EE) | small molecules | FDA | 2022-06-03 | — | Afimmune |
Inclacumab | antibodies | FDA | 2022-05-24 | — | Global Blood Therapeutics, Inc. |
a hemoglobin S polymerization inhibitor | small molecules | FDA | 2022-05-16 | — | Global Blood Therapeutics, Inc. |
(S)-Pociredir | small molecules | EMA | 2022-03-16 | — | Pharma Gateway AB |
naproxcinod | small molecules | FDA | 2022-02-28 | — | Fera Pharmaceuticals, LLC |
Pociredir | small molecules | FDA | 2022-02-10 | — | Fulcrum Therapeutics, Inc. |
gene-corrected (gc) HBB beta-globin gene variant for SCD drug product | combination | FDA | 2021-11-23 | — | Kamau Therapeutics, Inc. |
2-(2-{[2-(1H-benzimidazol-2-yl)ethyl]amino}ethyl)-N-[(3-fluoropyridin-2-yl)methyl]-1,3-oxazole-4-carboxamide trihydrochloride | small molecules | EMA | 2021-02-19 | — | Vifor France S.A. |
Autologous CD34+ hematopoietic stem and progenitor cells transfected with zinc finger nuclease mRNAs SB-mRENH1 and SB-mRENH2 | gene editing enzymes | EMA | 2021-02-19 | — | Yes Pharmaceutical Development Services GmbH |
ferroportin inhibitor | small molecules | FDA | 2021-01-25 | — | Vifor Pharma, Inc. |
pyrindinyl benzaldehyde | small molecules | FDA | 2021-01-07 | — | Illexcor Therapeutics, LLC |
Autologous CD34+ cells transduced ex vivo with a lentiviral vector containing a modified gamma-globin gene | gene therapies | EMA | 2020-11-13 | — | PPD Bulgaria EOOD |
mitapivat | small molecules | FDA | 2020-11-12 | — | Agios Pharmaceuticals, Inc. |
Rifaximin | small molecules | FDA | 2020-10-28 | — | Salix Pharmaceuticals, Inc. (a division of Bausch Health US, LLC) |
Decitabine, tetrahydrouridine | small molecules | EMA | 2020-10-19 | — | Novo Nordisk A/S |
(S)-1-(5-((2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-7-yl)sulfonyl)-3,4,5,6-tetrahydropyrrolo[3,4-c]pyrrol-2(1h)-yl)-3-hydroxy-2-phenylpropan-1-one | small molecules | EMA | 2020-10-19 | — | Novo Nordisk A/S |
L-citrulline | small molecules | FDA | 2020-10-07 | — | Asklepion Pharmaceuticals, LLC |
rADAMTS13 / apadamtase alfa (INN) | proteins | FDA | 2020-09-28 | — | Takeda Pharmaceuticals U.S.A., Inc. |
Hemopexin (Human) | proteins | FDA | 2020-09-23 | — | CSL Behring |
a recombinant humanized Fc effector function null IgG1 antibody with kappa light chains (IgG1) that selectively binds to E-selectin to inhibit binding to cellular proteins containing carbohydrate structures with a sialyl Lewis X (sLex) deter | antibodies | FDA | 2020-09-18 | — | Pfizer Inc. |
6-{(1S)-1-[(2-Amino-6-fluoroquinolin-3-yl)oxy]ethyl}-5-(1H-pyrazol-1-yl)pyridin-2(1H)-one | small molecules | FDA | 2020-09-18 | — | Pfizer, Inc. |
Tovinontrine | small molecules | EMA | 2020-08-21 | — | [INACTIVE] TMC Pharma (EU) Limited |
Hemopexin, human | proteins | EMA | 2020-07-27 | — | CSL Behring GmbH |
exagamglogene autotemcel [Casgevy] | combination | FDA | 2020-05-11 | 2023-12-08 | Vertex Pharmaceuticals Inc. |
Sodium Nitrite | small molecules | FDA | 2020-03-25 | — | AdimaBio LLC |
etavopivat | small molecules | FDA | 2020-02-19 | — | FORMA Therapeutics, Inc. |
Autologous CD34+ cells transduced with gamma globin lentiviral vector | gene therapies | FDA | 2020-01-14 | — | Cincinnati Children’s Hospital Medical Center |
Autologous CD34+ hematopoietic stem cells with a CRISPR-edited erythroid enhancer region of the BCL11A gene [Casgevy] | combination | EMA | 2020-01-09 | 2024-02-12 | Vertex Pharmaceuticals (Ireland) Limited |
Autologous CD34+ hematopoietic stem and progenitor cells transfected with zinc finger nuclease messenger RNAs SB-mRENH1 and SB-mRENH2 | gene editing enzymes | FDA | 2019-06-11 | — | Sangamo Therapeutics, Inc. |
deferoxamine | small molecules | FDA | 2019-03-15 | — | Theris Medical |
Benserazide hydrochloride | small molecules | EMA | 2019-01-11 | — | Isabelle Ramirez |
olinciguat | small molecules | FDA | 2018-06-04 | — | Cyclerion Therapeutics, Inc. |
Docosahexaenoic acid ethyl ester | small molecules | EMA | 2018-03-21 | — | TurnKey PharmaConsulting Ireland Limited |
sirolimus | small molecules | FDA | 2018-03-13 | — | Rare Partners srl Impresa Sociale |
Sirolimus | small molecules | EMA | 2018-01-17 | — | Rare Partners srl Impresa Sociale |
Decitabine and tetrahydrouridine | small molecules | EMA | 2017-06-20 | — | Ulrich Muehlner |
6-[(3S,4S-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl]-3-tetrahydropyran-4-yl-7H-imadazo[1,5-a]pyrazin-8-one | small molecules | FDA | 2017-01-31 | — | Imara Inc. |
Hepcidin | peptides | EMA | 2016-11-18 | — | La Jolla Pharmaceutical II B.V. |
2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde [Oxbryta] | small molecules | EMA | 2016-11-18 | 2022-02-15 | Pfizer Europe MA EEIG |
decitabine and tetrahydrouridine | small molecules | FDA | 2016-09-19 | — | Novo Nordisk Inc. |
dodecafluoropentane emulsion | other | FDA | 2016-02-11 | — | NuvOx Pharma |
Voxelotor [Oxbryta] | small molecules | FDA | 2015-12-29 | 2019-11-25 | Global Blood Therapeutics, Inc. |
prasugrel hydrochloride | small molecules | FDA | 2015-05-26 | — | Eli Lilly |
docosahexaenoic acid | small molecules | FDA | 2015-04-27 | — | Micelle BioPharma, Inc. |
sevuparin | small molecules | FDA | 2015-03-17 | — | Modus Therapeutics |
hydroxyurea | small molecules | FDA | 2015-03-16 | — | Ebelle D'Ebelle Pharmaceuticals LLC |
5-(hydroxymethyl)-2-furaldehyde [BAX 555] | small molecules | EMA | 2015-02-12 | — | BAXALTA INNOVATIONS GmbH |
Sevuparin sodium | other | EMA | 2015-02-12 | — | Modus Therapeutics AB |
pegylated carboxyhemoglobin bovine | proteins | FDA | 2015-01-15 | — | Prolong Pharmaceuticals, LLC |
6-((3S,4S)-4-Methyl-1-pyrimidin-2-ylmethyl-pyrrolidin-3-yl-1-(tetrahydro-pyran-4-yl)-1,5-dihydro-pryazolo[3,4-d]pyrimidin-4-one | small molecules | FDA | 2014-09-04 | — | Cardurion Pharmaceuticals, Inc. |
Betibeglogene autotemcel [Zynteglo] | gene therapies | EMA | 2014-04-29 | — | bluebird bio (Netherlands) B.V. |
lovotibeglogene autotemcel [Lyfgenia] | gene therapies | FDA | 2014-02-26 | 2023-12-08 | Genetix Biotherapeutics Inc. |
human haptoglobin | proteins | FDA | 2013-11-19 | — | BioProducts Laboratory Limited |
Rivipansel | small molecules | EMA | 2013-08-05 | — | FGK Representative Service GmbH |
hydroxycarbamide (hydroxyurea) [Siklos] | small molecules | FDA | 2013-07-24 | 2017-12-21 | Theravia Pharma |
recombinant humanized IgG1k monoclonal antibody to human invariant T cell receptor (iTCR) | antibodies | FDA | 2013-04-12 | — | NKT Therapeutics, Inc. |
Poloxamer 188 [ANX-188 (purified poloxamer 188) Injection] | small molecules | EMA | 2013-03-12 | — | Theradex (Europe) Limited |
extract of sorghum bicolor extract | other | FDA | 2012-11-19 | — | Invenux, LLC |
carbon monoxide | small molecules | FDA | 2012-09-28 | — | Hillhurst Biopharmaceuticals, Inc. |
Crizanlizumab [Adakveo] | antibodies | EMA | 2012-08-09 | — | Novartis Europharm Limited |
Human erythrocytes encapsulating inositol hexaphosphate | small molecules | EMA | 2012-07-04 | — | ERYtech Pharma S.A. |
Levoglutamide | small molecules | EMA | 2012-07-04 | — | Emmaus Medical Europe Limited |
Human haptoglobin | proteins | EMA | 2011-12-09 | — | Kedrion S.p.A. |
pentosan polysulfate sodium | small molecules | FDA | 2011-09-16 | — | Vanguard Therapeutics, Inc. |
Deferiprone | small molecules | EMA | 2011-02-23 | — | Chiesi Farmaceutici S.p.A. |
pegylated carboxyhemoglobin | proteins | FDA | 2010-10-21 | — | Sangart, Inc. |
Pegylated carboxyhaemoglobin | proteins | EMA | 2009-11-26 | — | Voisin Consulting Life Sciences |
2,2-dimethylbutyric acid, sodium salt | small molecules | EMA | 2009-03-18 | — | Isabelle Ramirez |
(1R,3R,4R,5S)-3-O-[2-O-benzoyl-3-O-(sodium(2S)-3-cyclohexyl-propanoate- | small molecules | FDA | 2009-02-17 | — | GlycoMimetics, Inc. |
pentosan polysulfate sodium | small molecules | FDA | 2008-11-21 | — | TRF Pharma, Inc. |
nitric oxide | small molecules | FDA | 2008-09-05 | — | Mallinckrodt Pharmaceuticals Ireland Ltd. |
sodium 2, 2 dimethylbutyrate | small molecules | FDA | 2008-07-25 | — | HemaQuest Pharmaceuticals, Inc. |
crizanlizumab [ADAKVEO] | antibodies | FDA | 2008-07-22 | 2019-11-15 | Novartis Pharmaceuticals Corporation |
varespladib sodium | small molecules | FDA | 2007-11-19 | — | Anthera Pharmaceuticals, Inc. |
sodium nitrite | small molecules | FDA | 2007-04-02 | — | Hope Pharmaceuticals |
5-hydroxymethyl-2-furfuraldehyde | small molecules | FDA | 2006-05-26 | — | Baxalta US, Inc. |
Extract of Sorghum bicolour leaf, Pterocarpus osun stem, Piper guineense seed and Caryophylli flower | other | EMA | 2005-08-26 | — | Xechem UK Ltd |
oral unfractionated heparin | small molecules | FDA | 2004-01-29 | — | TRF Technologies, Inc. |
niprisan | other | FDA | 2003-08-15 | — | Xechem International, Inc. |
Hydroxycarbamide [Siklos] | small molecules | EMA | 2003-07-09 | — | [INACTIVE] Addmedica |
N-[4-bromo-2-(1H-1,2,3,4-tetrazol-5-yl)phenyl]-N'-[3,5-bis(trifluoromethyl)phenyl]urea | small molecules | FDA | 2002-05-13 | — | NeuroSearch A/S |
L-glutamine [Endari] | small molecules | FDA | 2001-08-01 | 2017-07-07 | Emmaus Medical, Inc. |
Bis(4-fluorophenyl)phenylacetamide | small molecules | FDA | 2000-03-02 | — | ICAgen Inc. |
Fructose-1,6-diphosphate | small molecules | FDA | 1998-05-29 | — | Questcor Pharmaceuticals, Inc. |
Clotrimazole | small molecules | FDA | 1995-04-24 | — | Brugnara, Carlo M.D. |
Arginine butyrate | small molecules | FDA | 1994-05-25 | — | Vertex Pharmaceuticals Inc. |
sodium phenylbutyrate | small molecules | FDA | 1992-07-02 | — | Medicis Pharmaceutical Corp. |
Synthetic derivative of 16-hydroxy-9Z, 12Z, 14E-octadecatrienoic acid | small molecules | FDA | 1991-10-24 | — | Omex International, Inc. |
Lysine acetylsalicylate injectable | small molecules | FDA | 1989-08-01 | — | G.D. Searle & Company |
poloxamer 188 (purified) | small molecules | FDA | 1989-06-27 | — | Mast Therapeutics Inc. |
Cetiedil citrate injection | small molecules | FDA | 1988-12-22 | — | Baker Cummins Pharmaceuticals, Inc. |
substituted benzaldehyde that binds to the oxy-conformation of Hb between amino terminal residues of the alpha-subunits | small molecules | FDA | 1987-10-23 | — | Burroughs Wellcome Company |