Kisho

Kisho is an information platform, not a medical provider. Nothing on this site constitutes medical advice, diagnosis, or treatment recommendations. All content is aggregated from publicly available sources (including ClinicalTrials.gov, PubMed, FDA.gov, and Orphanet) and is provided for informational purposes only. Clinical trial eligibility, treatment decisions, and any health-related actions should always be discussed with a qualified healthcare professional. Kisho does not endorse any specific therapy, organization, or clinical trial. Terms of use · Privacy policy

sickle cell disease - Clinical Profile, Treatments & Trials | Kisho | Kisho

Clinical Presentation

Built from Human Phenotype Ontology (HPO) phenotype annotations and GeneReviews clinical descriptions. Features represent findings documented across known cases — not an exhaustive list of possible symptoms.

Features include always present findings: Ongoing breakdown of red blood cells (chronic hemolytic anemia); and very common findings: Red blood cell destruction (hemolytic anemia), Recurrent infections, and Pain. 48 total HPO annotations.

Organ System	Phenotype Count	Example Features
Blood and immune system	16	Recurrent bacterial infections, Red blood cell destruction (hemolytic anemia), Increased tendency for red blood cells to sickle (increased red cell sickling tendency)
Digestive system	9	Enlarged liver (hepatomegaly), Cholelithiasis, Blocked blood flow in the spleen (splenic infarction)
Heart and blood vessels	7	Stroke, Enlarged heart (cardiomegaly), Hypertension
Kidneys and urinary system	5	Reduced kidney function (renal insufficiency), Blood in the urine (hematuria), Priapism
Brain and nerves	4	Stroke, Pain, Nervous system problems (abnormality of the nervous system)
Eyes	3	Damage to the retina (retinopathy), Hyphema, Retinal arterial occlusion
Bones and joints	3	Weak and brittle bones (osteoporosis), Bone infection (osteomyelitis), Bone tissue death from poor blood supply (avascular necrosis)
Lab test results	3	Elevated creatinine (kidney function marker) (elevated circulating creatinine concentration), High bilirubin levels (unconjugated hyperbilirubinemia), Elevated LDH (tissue damage marker) (increased circulating lactate dehydrogenase concentration)
Lungs and breathing	2	Low blood oxygen levels (hypoxemia), High blood pressure in lung arteries (pulmonary arterial hypertension)
Arms and legs	1	Painful, swollen finger (finger dactylitis)
Skin	1	Skin ulcer

GeneReviews

Clinical Guidance

The clinical manifestations of sickle cell disease (SCD) result from intermittent episodes of microvascular occlusion leading to tissue ischemia/reperfusion injury and chronic hemolysis, both of which contribute to multiorgan dysfunction. The severity of disease manifestations varies, even in individuals with the same HBB pathogenic variants. Vaso-occlusive events are associated with ischemia/reperfusion damage to tissues that lead to pain and acute or chronic injury affecting any organ system. The bones/marrow, spleen, liver, brain, lungs, kidneys, eyes, and joints are often affected. The biologic markers associated with the "vaso-occlusive phenotype" include the following :

Source: GeneReviews — "Sickle Cell Disease"

Explore clinical features

Treatment

Compiled from FDA-approved drug records, orphan drug designations, and FDA Adverse Event Reporting System (FAERS) safety data. GeneReviews management guidance is included where available.

5 FDA-approved treatments are available for sickle cell disease, including exagamglogene autotemcel (Casgevy, approved 2023), lovotibeglogene autotemcel (Lyfgenia, approved 2023), and HYDROXYUREA (XROMI, approved 2024). 2 previously approved treatments have been withdrawn from the market. An additional 59 compounds hold orphan drug designation.

Approved Therapies

Brand Name	Generic Name	Mechanism	Approved	Market Status
XROMI	HYDROXYUREA	Blocks Ribonucleoside-diphosphate reductase RR1	2024	Available
Casgevy	exagamglogene autotemcel	Gene Editing Negative Modulator of B-cell lymphoma/leukemia 11A	2023	Available
Lyfgenia	lovotibeglogene autotemcel	Exogenous Gene of Hemoglobin subunit beta	2023	Available
FERRIPROX	DEFERIPRONE	Iron Chelating Activity	2020	Available
OXBRYTA	VOXELOTOR	Enhances the activity of Hemoglobin HbA	2019	Withdrawn for safety reasons
ADAKVEO	CRIZANLIZUMAB	Blocks P-selectin	2019	Withdrawn (insufficient effectiveness)
SIKLOS	HYDROXYUREA	Blocks Ribonucleoside-diphosphate reductase RR1	2017	Available
ENDARI	GLUTAMINE	—	2017	Available
DROXIA	HYDROXYUREA	Blocks Ribonucleoside-diphosphate reductase RR1	1967	Available

Safety Note: OXBRYTA (VOXELOTOR): Voluntarily withdrawn by Pfizer after post-marketing data showed higher mortality and vaso-occlusive crisis rates vs placebo.

Safety Note: ADAKVEO (CRIZANLIZUMAB): US approval voluntarily withdrawn by Novartis after Phase III STAND trial failed to show clinical benefit vs placebo. EMA and MHRA previously revoked approvals.

Orphan Drug Designations

The following drugs have received orphan drug designation from the FDA for sickle cell disease. Orphan designation reflects regulatory interest and does not indicate approval for treatment.

Brand Name	Generic Name	Sponsor	Designated	Exclusivity End	Designation Status
fetal hemoglobin activator cereblon (CRBN) E3 ligase-modulating drug	fetal hemoglobin activator cereblon (CRBN) E3 ligase-modulating drug	Bristol-Myers Squibb	2025	—	Designated
(lE, 6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6- heptadiene-3,5-dione)	(lE, 6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6- heptadiene-3,5-dione)	Vascarta Inc.	2025	—	Designated

Adverse Event Profiles

FDA adverse event reports (FAERS) include all outcomes reported during treatment and do not establish causation. Report counts reflect all approved indications for each drug, not only this disease.

20,657 adverse event reports have been filed with the FDA for HYDROXYUREA (across all indications). Most commonly reported: alopecia, dizziness, and abdominal discomfort.

22 adverse event reports have been filed with the FDA for exagamglogene autotemcel (across all indications). Most commonly reported: sickle cell anaemia with crisis, abdominal pain, and device related thrombosis.

9 adverse event reports have been filed with the FDA for lovotibeglogene autotemcel (across all indications). Most commonly reported: mucosal inflammation, ageusia, and alopecia.

GeneReviews

Management Guidelines

Management guidelines for sickle cell disease (SCD) have been published [, , , , , , , , ]; see also the American College of Emergency Physicians guideline available online.

Evaluations Following Initial Diagnosis

To establish the extent of end-organ damage and needs in an individual diagnosed with SCD, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Table 3.

Recommended Evaluations Following Initial Diagnosis in Individuals with Sickle Cell Disease

System/Concern | Evaluation | Comment

Hematology

| Hematologist consultation |

CBC reticulocyte count
Measurement of HbF (%)
Thalassemia testing: hemoglobin electrophoresis or HPLC inclusion body prep
RBC genotyping so that antigen-matched blood may be given if transfusion is urgently needed

| • Baseline laboratory studies should be done in infants ≥12 mos

During childhood HLA typing should be offered to affected person all full sibs that are unaffected or carry a hemoglobin trait.

GeneReviews

Clinical Guidance

Education for individuals with SCD involves learning how to control one's environment to minimize the chance of exacerbations. Environmental controls include avoiding the following:

Dehydration
Extremes of temperature (e.g., swimming in cold water, which can trigger a pain episode)
Physical exhaustion
Extremely high altitude without oxygen supplementation
Trauma
Infection
Cocaine. While alcohol and illegal drugs are never endorsed, cocaine and its derivatives, with their vasoconstrictive and cardiac stimulation effects, are particularly dangerous drugs in the setting of SCD.
The analgesic meperidine, which should be avoided as first-line therapy because of potential central nervous system toxicity

Source: GeneReviews — "Sickle Cell Disease"

GeneReviews

Therapies Under Investigation

Increased understanding of SCD pathophysiology has led to the development of drugs that target different pathways as well as attempts to improve medications currently in use. While not comprehensive, several promising agents targeting different pathways are presented here, with emphasis on those that are in Phase II/III clinical trials [, , , ]. Allosteric changes in hemoglobin to decrease HbS polymerization. HbS polymerizes in the T (tense) conformation associated with deoxygenation, but not the R (relaxed) conformation associated with oxygenation. The drug voxelotor (withdrawn from the market in 2024; see FDA Alert) binds a subpopulation of hemoglobin leading to a conformational change stabilizing the R state, decreasing polymerization, increasing hemoglobin, and decreasing hemolysis.

Source: GeneReviews — "Sickle Cell Disease"

Clinical Trials

288 trials found

Explore Trials

Prognosis

Based on GeneReviews surveillance recommendations, HPO phenotype frequency and severity annotations, and published prevalence estimates from Orphanet and OMIM.

GeneReviews

Surveillance Guidelines

Affected individuals should be seen routinely for evaluation of SCD-related comorbidities. Surveillance should be tailored to an individual's specific genotype and clinical history. Routine age-dependent screening allows for early detection and treatment of end-organ damage. While the National Heart, Lung, and Blood Institute in the US released guidelines for surveillance, the recommendations are not complete, and some have been modified since publication. The American Society of Hematology has been developing multiple sets of guidelines, but gaps remain, especially for genotypes other than Hb S/S and Hb S/0-thalassemia. The following are general guidelines compiled from several sources (see also ). Table 5. Recommended Surveillance for Individuals with Sickle Cell Disease

System/Concern	Evaluation1	Frequency
Hematology	CBC w/differential reticulocyte count	Annually as needed RBC genotyping (or phenotyping if needed urgently) so that antigen-matched blood may be given if transfusion is needed
cerebral infarcts	Transcranial Doppler	Annually from age 2-16 yrs in all children w/Hb S/S Hb S/0-thalassemia; Children w/normal velocities require ongoing annual eval. Developmental assessment
lung disease	PFTs	In those w/history of ...

Source: GeneReviews — "Sickle Cell Disease"

Phenotype severity distribution: 1 always present feature, 3 very common features, 13 common features.

Estimated prevalence: 1-5 in 10,000 (Uncommon).

Research Landscape

Sourced from ClinicalTrials.gov and PubMed. Publication types are classified using NLM-curated article metadata; research type breakdowns reflect the nature of published work for this disease.

288 clinical trials registered, 131 recruiting. Interventions under study include other interventions, drug therapy, biologic therapy, and procedural interventions. Pipeline includes 10 PHASE4, 21 PHASE3, 47 PHASE2. Research is sponsored by a mix of industry and academic institutions.

NCT ID	Title	Phase	Sponsor	Status
[NCT07187973](https://clinicaltrials.gov/study/NCT07187973)	A Phase 1b, Open-Label Study of DISC-3405 in Participants With Sickle Cell Disease (SCD)	PHASE1	Disc Medicine, Inc	RECRUITING
[NCT06358638](https://clinicaltrials.gov/study/NCT06358638)	Sickle Cell Disease Transplant Using a Nonmyeloablative Approach for Patients With Anti-donor Red Cell Antibody	PHASE2	Children's National Research Institute	RECRUITING
[NCT06941389](https://clinicaltrials.gov/study/NCT06941389)	Comparing the Effectiveness of Matched Related Donor Hematopoietic Stem Cell Transplantation to Disease Modifying Therapy in Pediatric Patients With Sickle Cell Disease	—	University of Rochester	RECRUITING
[NCT05799118](https://clinicaltrials.gov/study/NCT05799118)	Study of the Role of Genetic Modifiers in Hemoglobinopathies	—	Cyprus Institute of Neurology and Genetics	RECRUITING
[NCT05099874](https://clinicaltrials.gov/study/NCT05099874)	Feasibility and Efficacy of Attentional-Control Training in Sickle Cell Disease	NA	Children's National Research Institute	RECRUITING

500 publications have been identified in PubMed for sickle cell disease. Research spans Review / Meta-Analysis (25%), Epidemiology / Natural History (21%), and Basic Science / Preclinical (11%).

Research Type	Count	% of Total
Research summaries	127	25%
Disease patterns and progression	107	21%
Laboratory research	53	11%
Patient case studies	52	10%
Clinical study results	51	10%
New treatment approaches	44

Recent Publications

Byrd J (2026). [PMID: 41207735](https://pubmed.ncbi.nlm.nih.gov/41207735/). *Pediatr Clin North Am*. [Review / Meta-Analysis]
Joudeh S (2026). [PMID: 42186668](https://pubmed.ncbi.nlm.nih.gov/42186668/). *Orthop Rev (Pavia)*. [Case Report / Case Series]
Lê GN (2026). [PMID: 42207175](https://pubmed.ncbi.nlm.nih.gov/42207175/). *Br J Haematol*. [Review / Meta-Analysis]
Feinstein MM (2026). [PMID: 41556216](https://pubmed.ncbi.nlm.nih.gov/41556216/). *Paediatr Anaesth*. [Epidemiology / Natural History]
Galadanci N (2026). [PMID: 42604637](https://pubmed.ncbi.nlm.nih.gov/42604637/). *Expert Opin Drug Saf*. [Review / Meta-Analysis]
Lilly L (2026). [PMID: 41269516](https://pubmed.ncbi.nlm.nih.gov/41269516/). *Adv Ther*. [Epidemiology / Natural History]
Casadessus E (2026). [PMID: 42194209](https://pubmed.ncbi.nlm.nih.gov/42194209/). *Children (Basel)*. [Review / Meta-Analysis]
Hoyt CR (2026). [PMID: 41207732](https://pubmed.ncbi.nlm.nih.gov/41207732/). *Pediatr Clin North Am*. [Review / Meta-Analysis]
Wang Z (2026). [PMID: 41815586](https://pubmed.ncbi.nlm.nih.gov/41815586/). *Cureus*. [Other]
Queen JR (2026). [PMID: 42575026](https://pubmed.ncbi.nlm.nih.gov/42575026/). *J Emerg Med*. [Case Report / Case Series]

Latest News & Developments

5 recent

View all

AI-curated news mentioning sickle cell disease

Updated Sep 15, 2026

Treatment & Clinical News•

Science & Discovery

•4 days ago(Sep 15)

Cell and Gene Therapies for Rare Disorders Poised for Breakthrough Growth Through 2036, Fueled by Innovation, Expanding Pipelines and Unmet Patient Needs

Hemophilia A, hemophilia B, sickle cell disease and spinal muscular atrophy accounted for a substantial share of commercial and clinical activity. The report, Cell and Gene Therapies in Rare Disorders - Market Insights, Epidemiology and Market Forecast - 2036, provides an assessment of historical and forecast epidemiology, treatment ... Hemophilia A, hemophilia B, sickle cell disease and spinal muscular atrophy accounted for a substantial share of commercial and clinical activity. The report, Cell and Gene Therapies in Rare Disorders - Market Insights, Epidemiology and Market Forecast - 2036, provides an assessment of historical and forecast epidemiology, treatment practices, market size, therapy uptake and competitive dynamics in the United States, Germany, France, Italy, Spain, the United Kingdom and Japan. Its market analysis covers the 2022-2036 period and examines standards of care, treatment algorithms, diagnosed patient populations, revenue trends, therapy-level market share, peak patient share, pricing, access and unmet medical needs. It also evaluates clinical and commercial opportunities across marketed products and emerging cell and gene therapy candidates. ... Growth is being supported by improved genetic screening, broader use of next-generation sequencing, increased rare disease awareness and stronger identification of patients with actionable molecular alterations. Rare disorder diagnosis frequently requires clinical assessment, laboratory testing, imaging and molecular confirmation. Next-generation sequencing, whole-exome sequencing and whole-genome sequencing increasingly support definitive diagnosis and patient stratification. Earlier identification is particularly important where treatment eligibility, disease stage or irreversible progression may influence therapeutic outcomes. Advances in gene editing, vectors and diagnostics are enabling one-time rare disease therapies, while access, manufacturing, delivery and long-term safety...

Treatment & Clinical News•

Science & Discovery

•4 days ago(Sep 15)

Cell and Gene Therapies for Rare Disorders Poised for Breakthrough Growth Through 2036, Fueled by Innovation, Expanding Pipelines and Unmet Patient Needs

Gene & Cell Therapy•

Science & Discovery

•5 days ago(Sep 14)

Gene Therapy: Symptoms, Causes, and Treatment Options | Acibadem Health Point

Examples often include inherited ... cell disease, where treatment aims to improve how blood cells are made or function. In ophthalmology, gene-based treatments may help selected inherited retinal disorders. In oncology, genetically modified immune cell therapies may be considered for some blood cancers when standard treatment is not enough. Gene therapy may also be discussed in relation to rare pediatric ... Examples often include inherited blood diseases such as thalassemia and some forms of sickle cell disease, where treatment aims to improve how blood cells are made or function. In ophthalmology, gene-based treatments may help selected inherited retinal disorders. In oncology, genetically modified immune cell therapies may be considered for some blood cancers when standard treatment is not enough. Gene therapy may also be discussed in relation to rare pediatric disorders, certain metabolic diseases, and conditions affecting muscles or the nervous system. Yes, some gene therapies are used in children, especially for rare inherited disorders diagnosed early in life. Eligibility depends on the specific condition, treatment approval, disease stage, and specialist assessment. In some cases, gene therapy is considered after standard options such as chemotherapy or other disease-specific treatments have been used. If a patient appears eligible, the care team explains the expected process, possible alternatives, and the need for follow-up. This may involve collection of stem cells or immune cells, laboratory modification, hospital-based infusion, supportive medicines, and repeat testing afterward. For some inherited blood disorders, treatment planning overlaps with advanced hematology care and transfusion management. No two patients follow the same gene therapy path. Some therapies are approved standard treatments for well-defined conditions, while others are available only through clinical trials. The best option depends on the disease, the specific mutation, age, previous treatment history, and the potential balance between benefit and risk. In inherited disorders, treatment may aim to restore a missing protein or improve cell function.

TOP STORY

Score: 95

Gene & Cell Therapy•

Science & Discovery

•5 days ago(Sep 14)

Will gene therapy be a sickle cell cure? | UCLA Health Jonsson Comprehensive Cancer Center

Yasmin Mbeyu is first pediatric ... approved therapy for the disease · Yasmin Mbeyu received a gift a day for 16 days leading up to her birthday. (Photo courtesy of Deborah Curtis) ... Yasmin Mbeyu, 15, is savoring normalcy after becoming the first pediatric patient at UCLA Health to undergo a novel gene therapy for ... Yasmin Mbeyu is first pediatric patient at UCLA Health to receive a newly approved therapy for the disease · Yasmin Mbeyu received a gift a day for 16 days leading up to her birthday. (Photo courtesy of Deborah Curtis) ... Yasmin Mbeyu, 15, is savoring normalcy after becoming the first pediatric patient at UCLA Health to undergo a novel gene therapy for sickle cell disease. Satiro De Oliveira, MD, a UCLA Health pediatric hematologist/oncologist who oversaw her treatment, said UCLA Health has been among the first U.S. medical centers to offer the Lyfgenia gene therapy since the Food and Drug Administration gave approval in late 2023. The therapy, available to patients 12 and older, provides particular benefit to young people such as Yasmin, who have decades to reap the benefits. “With someone younger, the body has not been hurt as much by the disease,” said Dr. Roughly 100,000 Americans are living with sickle cell disease, the most common genetic disease in the country. Sickle cell disease is caused by a gene mutation that makes abnormal hemoglobin, the protein the carries oxygen. As a result, the red blood cells become hard, sticky and crescent-shaped.

PubMed Rare Disease•

Science & Discovery

•6 days ago(Sep 13)

Parvovirus B19 infections in paediatric sickle cell disease patients: Genotype and hydroxyurea treatment influence disease severity.

A recent study highlights the impact of parvovirus B19 infections on pediatric patients with sickle cell disease, revealing that genotype and hydroxyurea treatment significantly influence disease severity. This research underscores the need for tailored treatment approaches in managing infections in this vulnerable population.

View all news for sickle cell disease

sickle cell disease

Overview

Clinical Presentation

Clinical Guidance

Explore clinical features

Genetic Landscape

Clinical Guidance

Diagnosis

Diagnostic Criteria

Differential Diagnosis

Treatment

Approved Therapies

Orphan Drug Designations

Adverse Event Profiles

Management Guidelines

Evaluations Following Initial Diagnosis

Hematology

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Patient Support

Financial & Access Support (External Programs)

Patient Advocacy Groups

Medical References

External Resources

OMIM

Orphanet

GARD

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

Liver

Latest News & Developments

Cell and Gene Therapies for Rare Disorders Poised for Breakthrough Growth Through 2036, Fueled by Innovation, Expanding Pipelines and Unmet Patient Needs

Cell and Gene Therapies for Rare Disorders Poised for Breakthrough Growth Through 2036, Fueled by Innovation, Expanding Pipelines and Unmet Patient Needs

Gene Therapy: Symptoms, Causes, and Treatment Options | Acibadem Health Point

Will gene therapy be a sickle cell cure? | UCLA Health Jonsson Comprehensive Cancer Center

Parvovirus B19 infections in paediatric sickle cell disease patients: Genotype and hydroxyurea treatment influence disease severity.