Sickle cell.
What changed?

RISE UP Phase 3 paper confirms haemoglobin response, but not fewer pain crises

Mitapivat produced a haemoglobin response of at least 1 g/dL in 56 of 138 participants (41%) versus 2 of 69 (3%) on placebo (p<0.0001). Annualised sickle-cell pain crises were 2.6 versus 3.1 (p=0.1213), so the pain-crisis co-primary endpoint was not met. Serious adverse events occurred in 28/138 (20%) versus 20/69 (29%).

The peer-reviewed controlled evidence strengthens the case that oral pyruvate-kinase activation can improve anaemia, while making clear it has not shown a statistically significant reduction in pain crises over the trial period.

The Lancet Phase 3 report, publisher date 24 October 2026, available online by 23 October; 207 randomised participants followed for primary endpoints through weeks 24 to 52. Trial NCT05031780 first posted 2 September 2021, last updated 23 June 2026, active but not recruiting, with actual primary completion 30 October 2025 and estimated final completion February 2030, exact day not stated

Manchester reports first UK sickle-cell Casgevy recipient has completed treatment

The trust says its first UK sickle-cell Casgevy recipient completed the intensive autologous cell-editing pathway, returned to school, and had no reported crises at the time of the report. The patient still receives care for muscle pain attributed to previous sickle-cell damage.

It is a concrete implementation milestone for England's managed-access pathway, showing treatment delivery through a specialist paediatric centre and regional and national sickle-cell panels.

Manchester University NHS Foundation Trust report posted 23 October 2026; discharge dated 29 June 2026; current status reported by the hospital, with no specified observation period after infusion

Boston BCL11A gene-editing pilot opens recruitment

The single-site, five-person pilot now lists recruiting at Boston Children's Hospital. It tests CRISPR/Cas9 editing of the BCL11A enhancer in a person's own blood-forming stem cells to raise fetal haemoglobin. The primary outcome is neutrophil engraftment by day 42, not freedom from pain crises.

Recruitment has opened for another investigational HbF-reactivation approach, but no participant outcome has been posted and it does not change the clinical evidence for established or approved products.

ClinicalTrials.gov NCT07708350, first posted 16 July 2026 and last update posted 21 October 2026; earlier 28 September public snapshot listed not yet recruiting

US centres agree minimum elements for gene-therapy delivery

The group classified 24 elements as essential and four as recommended for gene-therapy programme infrastructure, multidisciplinary care, delivery and longitudinal patient management.

It makes the specialist capacity and follow-up needed for intensive gene-therapy pathways more explicit as access expands.

Blood Advances online first 19 October 2026; modified Delphi process involving 64 US sickle-cell centres, with consensus predefined as at least 70% agreement

Brain MRI feature linked with existing silent infarcts in 929 children

Higher enlarged perivascular-space burden in the basal ganglia or whole brain was associated with prevalent silent cerebral infarcts after adjustment; the association was not seen for centrum semiovale burden alone.

The marker may help future work on identifying neurological risk in children with severe sickle-cell genotypes.

British Journal of Haematology online first 19 October 2026; T2 MRI re-analysis of 929 of 1,191 participants in the earlier Silent Cerebral Infarct Transfusion Trial

Planned pregnancy-transfusion trial withdrawn without enrolling anyone

The planned 50-person comparison of prophylactic red-cell transfusion with usual care during sickle-cell pregnancy was withdrawn. The sponsor's registry reason is 'no enrollment'; there are no participant outcomes.

This removes one anticipated randomised evidence source on a consequential pregnancy-care question.

ClinicalTrials.gov NCT06979492 first posted 20 May 2025; last update posted 19 October 2026; sponsor-reported withdrawal reason and zero actual enrollment

Longer transplant follow-up finds sustained improvement in cardiac imaging markers

After matched-sibling or haploidentical donor transplantation, cardiac MRI showed reductions in biventricular and left-atrial volumes and improvement in extracellular volume, an imaging surrogate for fibrosis. At 12 months, selected echocardiographic measures favoured transplant recipients over an age-matched disease-modifying-therapy group. A 2024 report from the same programme covered only the first 12 months.

The longer follow-up strengthens evidence that successful transplantation can improve sickle-cell-related cardiac remodelling, a serious complication, rather than only control pain crises.

British Journal of Haematology, online first 18 October 2026; serial cardiac imaging in 20 transplanted children and young adults, follow-up up to 36 months; age-matched non-randomised disease-modifying-therapy comparator at 12 months

Maryland virtual-reality crisis-pain pilot moves to recruiting status

The registry now lists recruitment at a Maryland infusion centre and increased estimated enrolment from 25 to 50. Participants are randomised to two of three headset experiences across two qualifying pain-crisis visits: 2D control, passive immersive 3D, or interactive immersive 3D. The primary measure is pain burden over 60 minutes. The estimated start moved from 1 August to 1 November 2026, primary completion from August to December 2027, and final completion from December 2027 to March 2028.

A live randomised comparison can test feasibility, tolerability and preliminary analgesic effects during acute care, but opening recruitment does not demonstrate benefit.

ClinicalTrials.gov NCT07674277; first posted 29 June 2026; last update posted 16 October 2026; one US site recruiting, 50 estimated adults

Small study explores a marker for missing HbS targets before red-cell exchange

Investigators combined each patient's daily HbS rise and haematocrit fall into a sickling pressure index. The pre-exchange HbS target was met at 34 of 48 low-index encounters versus 30 of 63 high-index encounters; the adjusted odds ratio was 2.65 (95% CI 1.07 to 6.59).

Routine apheresis measurements might help identify patients who need individualised exchange scheduling if the index is validated prospectively.

Transfusion, online first 16 October 2026; retrospective single-centre cohort of 19 patients and 115 chronic red-cell exchange procedures over 40 months

Larger sham-controlled acupressure study registered for chronic sickle-cell pain

Researchers registered a planned comparison of usual care plus active self-acupressure, usual care plus sham acupressure, and usual care alone for adults with chronic sickle-cell pain. The primary measures are pain intensity and interference after five weeks.

The sham arm and larger planned sample could test whether the symptom signal in a small 2025 exploratory study exceeds expectation and usual-care effects. Registration itself does not demonstrate benefit.

ClinicalTrials.gov NCT07875777, first posted and last updated 15 October 2026; randomized, participant-masked, three-arm study with 300 estimated participants; no outcomes reported

Review identifies barriers to sustainable prenatal and newborn sickle-cell screening

The synthesis found that programme durability depends on political and financial support and integration into existing care. Community knowledge and stigma shape screening acceptance, while prenatal and newborn testing offer different choices and consequences for families.

Brings together implementation evidence for early diagnosis in high-prevalence settings, where a positive test only helps when children can access continuing care.

BMC Global and Public Health, online first 8 October 2026; 18 qualitative papers from Angola, Cameroon, DR Congo, Ghana, Liberia, Nigeria, Senegal, Tanzania and Uganda; GRADE-CERQual used to assess themes

Long REACH analysis finds no infection increase during hydroxyurea treatment

Infection incidence and severity did not rise as children moved from screening through fixed-dose and escalated hydroxyurea. For non-malarial infections, the adjusted incidence rate ratio at maximum tolerated dose versus screening was 0.51 (95% CI 0.43 to 0.61).

Adds substantial long-term, four-country safety evidence addressing a barrier to hydroxyurea use in lower-resource paediatric care.

The Lancet Haematology, online first 7 October 2026; REACH phase 1/2 treatment trial, 606 treated children aged 1 to 10; 5,493 clinically diagnosed infections over 5,638 person-years

Small pregnancy cohort finds no detected antibody-risk difference by transfusion strategy

New red-cell antibodies were recorded in 1 of 26 chronic-transfusion pregnancies and 5 of 119 on-demand pregnancies, without a statistically significant difference. The authors retrospectively judged that 87% met ASH and 65% met BSH chronic-transfusion criteria, while 20% received chronic transfusion.

Adds data to a difficult pregnancy transfusion decision and suggests a gap between guideline criteria and practice in the studied cohort.

Transfusion, online first 7 October 2026; two-centre analysis of 145 pregnancies, 26 managed with chronic transfusion and 119 with on-demand transfusion

Luanda hospital reports high sickle-cell burden among chronic paediatric admissions

Sickle cell anaemia accounted for 97 of 262 eligible chronic-disease admissions (37.0%). Compared with other chronic-disease admissions, these children had longer median intensive-care stays (7 versus 3 days) and more red-cell transfusions (26% versus 5%).

Quantifies the local inpatient and resource burden of sickle cell anaemia in an underrepresented setting, supporting scrutiny of access to earlier and continuing care.

BMC Pediatrics, online first 7 October 2026; retrospective comparison of 262 chronic-disease paediatric admissions within 1,169 total admissions in 2024

UK multicentre eye study finds frequent advanced retinopathy in sickle cell disease

Among participants with the relevant measurements, 77/611 (12.6%) had visual impairment, 206/575 (35.8%) had stage 3 to 5 retinopathy and 253/551 (46.0%) had maculopathy. HbSC was associated with greater odds of stage 3 or higher retinopathy than HbSS (adjusted odds ratio 6.92, 95% CI 4.50 to 10.6).

The findings support evaluating risk-adapted retinal screening in UK adult services, particularly because advanced disease may cause visual loss before symptoms are noticed.

ASCAT 2026 abstract O72, first published online in British Journal of Haematology on 6 October; prospective cross-sectional study of 618 adults at 18 NHS hospitals

One UK hospital audit finds sickle-cell pain treatment often missed the 30-minute standard

Only 14/105 episodes (13.3%) received analgesia within 30 minutes of presentation; median time was 66 minutes. Pain was reassessed within 30 minutes in 20/105 episodes (19.0%). Delays occurred both before prescription and between prescription and administration.

The audit identifies specific local opportunities to improve delivery of an existing acute-care standard.

ASCAT 2026 abstract O06, first published online in British Journal of Haematology on 6 October; 105 admission episodes over four audit years

Small etavopivat cohort reports a transfusion signal and one fatal serious-event case

Three of four evaluable participants receiving simple transfusions had at least a 20% and at least a 33% reduction in red-cell units during any continuous 12-week interval versus baseline. Exchange-transfusion analysis was post hoc. One participant with concomitant conditions experienced four serious adverse events and died; the abstract does not establish whether etavopivat caused them.

Offers an early, hypothesis-generating signal for a group with substantial transfusion burden, while making safety and attribution questions visible.

ASCAT 2026 abstract O76, first published online in British Journal of Haematology on 6 October; GLADIOLUS phase 2 cohort of 13 chronically transfused participants with sickle cell disease

New transfusion analysis concerns voxelotor, which remains withdrawn

The authors report an adjusted difference of 1.31 fewer red-cell transfusions per patient-year in the change from baseline among those prescribed voxelotor versus matched non-users. The analysis addresses transfusion use, not the overall balance of crises, deaths and benefit that drove withdrawal.

Adds a historical observational signal about transfusion burden while illustrating why a favourable individual outcome cannot establish overall clinical benefit or restore a withdrawn medicine.

Accepted peer-reviewed manuscript, online first 6 October 2026; propensity-score-matched US claims analysis, 164 voxelotor-exposed people and 289 comparators; several authors affiliated with Pfizer

COALESCE late-effects study stops recruiting with 377 participants

The registry moved from recruiting to active, not recruiting. Its enrollment changed from 750 estimated to 377 actual participants. The study compares longer-term heart, lung and kidney measures after myeloablative curative therapies in children or nonmyeloablative transplant in adults with standard-care cohorts.

The smaller, now-closed cohort sets the scale of forthcoming late-effects evidence, relevant to weighing benefits and risks of intensive curative approaches.

ClinicalTrials.gov observational cohort NCT05153967, first posted 10 December 2021 and updated 6 October 2026; independent change history confirms the previous registry values

Côte d'Ivoire newborn screening and early-care study now lists a recruiting site

The current registry lists one Yopougon-area health centre as recruiting and a second sickle-cell centre as not yet recruiting. The study combines Gazelle point-of-care newborn screening with confirmatory testing and a package of early preventive and clinical care.

Tests whether linking a rapid newborn result to an early-care pathway can improve outcomes in a low-resource setting, beyond simply detecting the condition.

ClinicalTrials.gov Phase 4 single-group health-services registry; NCT07488520; update submitted 30 September and posted 5 October 2026; recruiting status at one site; estimated 120 infants

Kenyan Defence Forces hospital adds red-cell exchange capability

Defence Forces Memorial Hospital reports that it performed its first red-cell exchange on 2 October 2026 and can now offer this specialised procedure to eligible beneficiaries within its health system.

Adds a specialist transfusion capability at one Kenyan hospital that may reduce the need for outside referral for eligible patients.

Kenya Ministry of Defence account of the hospital's first red-cell exchange with its new apheresis equipment

Brief cognitive assessment tested in 440 adults with sickle cell disease

The study measured performance of French and English RUDAS in adults with sickle cell disease. A score below 27 had 83% specificity but only 50% sensitivity for neurocognitive disorder. Adjusting for education raised specificity to 89% while sensitivity fell to 45%.

The findings give services a more specific basis for considering a brief route to fuller cognitive evaluation, while showing why this score should not be treated as a rule-out test.

Peer-reviewed multicentre assessment of the Rowland Universal Dementia Assessment Scale in 440 adults; a prespecified subset received a multidisciplinary reference assessment

Three-state study finds gaps in the move to adult sickle-cell care

The authors reported that 42.4% met their transfer definition: at least two adult-provider outpatient encounters within 12 months after the last paediatric encounter. Among those meeting that definition, relatively few established adult haematology or sickle-cell specialist care.

The study puts a measurable number on an important care-continuity gap and supports closer scrutiny of specialist access during transition to adult services.

Peer-reviewed observational analysis of CDC Sickle Cell Data Collection records from three US states; 205 insured young people aged 15 to 20

Roche announces newborn-screening kit that includes an optional sickle-cell target

Roche says TIB MOLBIOL launched the LightMix Newborn TREC/SMN1/HBB kit for markets accepting the CE mark. It screens dried blood spots for three conditions, with an optional HBB codon-6 component associated with sickle cell disease and beta-thalassaemia.

A combined assay could give laboratories another screening option, but this announcement does not show that programmes have adopted it or that it improves diagnostic accuracy or patient outcomes.

Roche company announcement and manufacturer product information, not an independent screening-performance or implementation study

Red Cell Network funds specialist-nurse roles at Norfolk and Norwich and Lister hospitals

UCLH reported that its Red Cell Network is funding Clinical Nurse Specialist roles at Norfolk and Norwich University Hospital and Lister Hospital. It says the roles are already operating and identifying previously unmet needs.

This is a concrete example of specialist haemoglobinopathy support being funded at two local hospitals. It may help patients access expertise closer to home, but the size and measured effect of the change are not yet clear.

UCLH Red Cell Network service report, not a national staffing audit or patient-outcomes study

EMA consults on proposed clinical-trial standards for sickle-cell medicines

The EMA published a consultation draft on the clinical-development requirements for sickle-cell medicines. It focuses on confirmatory phase 3 trials, clinical endpoints, inclusion across relevant genotypes and longer-term safety assessment. Comments are due by 31 January 2027.

The proposal could shape how future sickle-cell trials are designed and what evidence supports European benefit-risk decisions. The original publication was 24 September; this tracker record is a later backfill, not a new 29 September regulatory action.

EMA draft regulatory guideline, not final guidance or evidence of treatment efficacy

Updated Cochrane overview finds strongest transfusion evidence for preventing stroke in high-risk children

The update brings together transfusion evidence across sickle-cell complications. For children and adolescents at high stroke risk, long-term red-cell transfusion probably reduces stroke compared with standard care (risk ratio 0.12, 95% confidence interval 0.03 to 0.49; two trials, 326 participants; moderate certainty). It may also reduce acute chest syndrome and painful crises in this group, but those findings have low certainty.

This makes clear which transfusion benefit is well supported and where evidence remains thin. It synthesises existing trials, rather than reporting a new trial or changing a treatment licence.

Updated Cochrane overview of 17 reviews; five reviews with usable transfusion comparisons included nine randomised trials and 1,502 participants

In-vivo viral delivery reaches stem cells and induces fetal globin in a sickle-cell model

Shielded lentiviral and alpha-retroviral vectors were injected into mobilized humanized mice. Gene marking reached up to 8.8% of human CD45-positive cells, then 70% after chemoselection, including 54% of stem cells. An erythroid-targeted RNA-interference construct reduced BCL11A and ZNF410 activity, raising fetal globin to 61.5% of beta-like globins in the model.

Delivering treatment directly to stem cells inside the body could eventually reduce the need for laboratory editing of collected cells. This approach uses viral gene transfer and gene silencing, not the CRISPR-Cas9 DNA cut used by Casgevy.

Peer-reviewed Cell Stem Cell study in mobilized humanized mice, not a human clinical trial

Mortality-risk model is tested in an independent adult sickle-cell cohort

Researchers trained a multi-task deep-learning model using baseline clinical measurements and three-year biomarker trajectories. Once trained, it required only baseline data. In a separate adult cohort it performed better than two comparator models for five-year mortality prediction. The published abstract does not provide an absolute performance estimate.

More accurate risk estimates could help identify people who may need closer follow-up or consideration of intensive treatment, if future prospective testing demonstrates useful and fair decisions.

Observational model development in 598 adults and external validation in a separate cohort of 383 adults

OneSCD global partnership formally launches during the UN General Assembly

OneSCD was formally launched at a UN General Assembly side event. Its stated role is to align partners around country-led sickle-cell care, sustainable financing and mutual accountability. The UN event sets out the partnership's aims but does not report a new funded programme, national rollout or treatment outcome.

A standing coordination mechanism could help move existing guidance and proven interventions into high-burden health systems. Its impact will depend on published commitments, funding, country plans and measured delivery.

United Nations-hosted launch event and recording; policy and implementation signal, not clinical evidence

French study shows diagnosis codes alone can misclassify sickle-cell disease and trait

Researchers processed 561,924 reports from 10,868 adults with a sickle-cell ICD-10 code. Among reports containing sickle-related terms, the method classified 6,234 people as having sickle-cell disease and 1,502 as having trait. Its positive predictive value was 94.0% in the manually reviewed sample, compared with 58.1% to 88.3% for diagnosis-code-only strategies.

Research based only on administrative codes can mix disease subtypes or include people with trait, distorting prevalence and outcome estimates. This validation offers a reproducible way to improve retrospective datasets.

Peer-reviewed validation of a rule-based clinical-text algorithm against manual review of 1,510 patients in five French specialist centres

Survey identifies family-building concerns and gaps around partner trait status

Researchers examined factors affecting family-building and discussions about genetic transmission. Eighty-six per cent of participants said they were comfortable discussing sickle cell disease with partners and 89% with doctors. Among participants who were dating or partnered, 65% said their partner did not know their sickle-cell-trait status. Forty-five per cent reported receiving genetic counselling, and 12% of that group said it influenced their family-building perspective. Concerns included personal health, pregnancy, financial and family support, and genetic transmission.

The findings identify a gap between willingness to discuss genetic risk and partners knowing their trait status. They support research into more consistent, practical reproductive and genetic counselling for women and men with sickle cell disease.

Peer-reviewed secondary analysis of survey responses from 91 adults with sickle cell disease aged 21 to 39 at one US medical centre

Systematic review projects a large paediatric sickle-cell moyamoya burden despite sparse evidence

The review found 14 eligible studies, nine from the Americas and only one from Africa. Across 2,045 children with sickle cell disease in the included evidence, 1.5% were diagnosed with moyamoya syndrome. The authors projected 36,587 cases worldwide, including 32,189 in Africa, and estimated that 18,219 children could warrant specialist consideration for revascularisation. Among 279 children with both conditions described in surgical evidence, 49.8% underwent revascularisation.

The review highlights a mismatch between the likely neurological burden in high-prevalence regions and access to transcranial Doppler screening, imaging, specialist medical management and paediatric neurovascular surgery. It frames workforce and diagnostic capacity as part of stroke prevention.

Peer-reviewed PRISMA systematic review of 14 studies, combined with 2021 global disease estimates

Children with sickle cell disease and acute pancreatitis had longer stays and more procedures

Children with sickle cell disease had a median hospital stay of four days compared with three days among children without sickle cell disease. Thirty-one per cent received transfusions compared with 3%, 21% underwent endoscopic intervention compared with 8%, and 33% underwent cholecystectomy compared with 11%.

The study quantifies the additional hospital and procedural burden when acute pancreatitis occurs in children with sickle cell disease. It may help define questions for earlier gallstone detection, coordinated haematology and gastroenterology care, and future comparative research.

Peer-reviewed retrospective Pediatric Health Information System analysis of 18,213 children admitted with acute pancreatitis, including 286 with sickle cell disease

Texas Medicaid study finds persistent diagnosed-depression burden in adults with sickle cell disease

Researchers compared annual diagnosed-depression rates among adults aged 18 to 63 with sickle cell disease and the wider adult Texas Medicaid population. The sickle-cell groups included 2,417 to 2,707 people per year. Diagnosed depression rose from 20.3% in 2016 to 25.7% in 2020 and remained above 25% in 2022. The annual rate was 1.6 to 1.8 times the rate in the wider Medicaid population. Women had higher absolute rates, while adults aged 18 to 26 had the largest relative difference from peers without sickle cell disease.

The study adds longitudinal evidence that mental-health burden remained high even after the wider Medicaid rate fell from its 2020 peak. It supports closer attention to depression identification and care alongside physical sickle-cell management, especially for younger adults and women.

Peer-reviewed retrospective analysis of Texas Medicaid administrative claims from January 2016 to July 2023

Direct sickle-mutation correction reaches peer-reviewed manufacturing and preclinical publication

CRISPR_SCD001 uses CRISPR-Cas9 homology-directed repair and a donor DNA template to correct the pathogenic HBB sickle mutation in a person's own blood-forming stem cells. Clinical-scale cell products averaged 22% corrected HBB alleles and 51% disrupted alleles. Edited erythroid cultures reduced sickle haemoglobin from 89% to 22%, while approximately 20% correction persisted after engraftment in NBSGW mice. The linked US trial is recruiting at UCLA and UCSF, started on 22 August 2025 and estimates completion on 1 March 2030.

Unlike Casgevy, which disrupts a BCL11A control region to reactivate fetal haemoglobin, this approach attempts to repair the sickle mutation itself. The publication provides a reproducible manufacturing and preclinical evidence package for an approach now entering human testing.

Peer-reviewed manufacturing and preclinical study linked to a recruiting nine-person, single-group Phase 1/2 US trial

New Phase 4 platform trial will compare eight hospital pain-management strategies

The French PAMAVOC trial has been registered to compare eight inpatient strategies for adults admitted with a vaso-occlusive crisis requiring intravenous morphine. Every group receives paracetamol and morphine patient-controlled analgesia; experimental groups add ketamine, nefopam, tramadol or ketoprofen in different combinations. The primary endpoint is time from randomisation to stopping intravenous opioids, measured for up to 14 days.

A shared adaptive platform could compare several commonly considered adjunct pain treatments within one protocol. Its size and randomisation may produce more useful comparative evidence than a series of small separate studies.

New 400-person randomised open-label adaptive platform-trial registry record, with no results

Cumulative physiological stress measure is associated with pain crises and emergency care

Researchers calculated an allostatic-load index, intended to capture cumulative physiological dysregulation, from 27 biomarkers in 129 adults. People in the highest category had 4.1 times the odds of pain-related vaso-occlusive episodes and 6.3 times the odds of emergency-department use. Higher load was also associated with unemployment, lower social support, poverty, lower educational attainment and disadvantaged neighbourhoods.

The study connects clinical burden with a measurable combination of biological stress and social conditions. It may help shape further research into risk and interventions that address both disease biology and social determinants.

Peer-reviewed cross-sectional analysis of 27 biomarkers in 129 adults with sickle cell disease

Mouse study tests induced haptoglobin as a way to reduce damage from free haemoglobin

Researchers used gene therapy to make liver cells express haptoglobin, a protein that binds free haemoglobin, in a sickle-cell mouse model. Treated animals showed improvements in several blood measures, a reduced compensatory red-cell response and less spleen enlargement.

The work explores a different therapeutic target: limiting damage linked to free haemoglobin released during chronic haemolysis rather than editing the sickle mutation or increasing fetal haemoglobin.

Peer-reviewed sickle-cell mouse study using gene therapy to induce haptoglobin expression

US study describes postpartum transfusion, readmission and breastfeeding after sickle-cell pregnancy

Researchers reviewed postpartum care after 37 deliveries in people with sickle cell disease at a US academic centre. Thirteen of 37 deliveries involved a transfusion in the first postpartum week, five of 37 had postpartum haemorrhage of at least 1,000 mL, and five of 36 led to readmission within six weeks, most often for a vaso-occlusive crisis. Breastfeeding was reported at six weeks by 23 of 33 and at approximately six months by 12 of 34.

The paper adds dated, specific evidence that sickle-cell care needs to continue beyond delivery, including attention to haematological complications and feeding support. It does not show that a particular transfusion strategy or breastfeeding intervention improves outcomes.

Peer-reviewed retrospective single-centre cohort of 37 deliveries from 2015 to 2025

Preprint explores in vivo editing and EPOR-linked expansion of corrected blood cells

Researchers used base and prime editing to introduce an EPOR W439* variant intended to give edited erythroid cells a growth advantage. Their platform paired this with fetal-haemoglobin approaches or correction of the sickle-cell mutation. The in vivo disease-model result used beta-thalassaemia patient cells in humanised mice with gamma-globin gene addition: over 70% of erythroid cells were HbF-positive, and several disease markers improved. Vectors were given intravenously after stem-cell mobilization and cytokine prophylaxis, without later drug selection.

The approach tackles a major in vivo gene-editing problem: too few corrected blood stem cells may persist to produce a useful proportion of healthy red cells. If replicated and shown safe, preferential expansion could help, but this is only an early research strategy.

Unreviewed preprint: laboratory experiments in an erythroid cell line and primary human CD34+ cells, plus humanised mice engrafted with beta-thalassaemia patient cells

UK-recruiting HIBISCUS 2 trial updates registry eligibility text and planned enrolment

The ClinicalTrials.gov record for HIBISCUS 2 changed its stated inclusion range from 1 to 15 documented vaso-occlusive crises in the 12 months before screening to 2 to 15. Estimated total enrolment rose from 408 to 510. The overall status remains recruiting, including at six listed UK facilities. Estimated primary completion remains 27 August 2027 and estimated final completion remains 12 August 2029. No results are posted.

Prospective participants need accurate public eligibility information. The larger target changes the planned scale of this placebo-controlled efficacy study, but does not mean etavopivat has been shown to work.

ClinicalTrials.gov Phase 3 randomised trial record, consecutive registry versions 19 and 20

Final Casgevy sickle-cell trial results posted in ClinicalTrials.gov

The registry first posted results for NCT03745287 on 16 September 2026. The study enrolled 63 people, started mobilisation in 58, infused 46 with exagamglogene autotemcel (Casgevy), and recorded 45 completing the study. Its primary endpoint, no severe vaso-occlusive crisis for at least 12 consecutive months, was met by 42 of 46 treated participants, or 91.3% (95% confidence interval 79.2% to 97.6%), assessed from 60 days after the last red-cell transfusion within up to two years after infusion. Serious adverse events affected 22 of 46 treated participants. One all-cause death was reported.

This is the first public results posting in the trial registry for the pivotal sickle-cell study, adding a full treated-population denominator and detailed safety outcomes to earlier publications and company summaries. The results reinforce a substantial reduction in severe crises for many treated people, while showing that not everyone met the endpoint and that treatment is intensive.

Sponsor-reported final results in ClinicalTrials.gov from the single-arm Phase 2/3 CLIMB-121 study, with an earlier FDA clinical assessment of the reported death

Large Quebec study separates pregnancy outcomes with and without sickle cell crises

Researchers compared pregnancy outcomes among people with sickle cell anaemia who did or did not have a recorded crisis. Compared with pregnancies without a sickling disorder, crises were associated with severe maternal morbidity, relative risk 8.50, peripartum sepsis, relative risk 12.64, and acute renal failure, relative risk 32.37. Crises were also associated with preterm birth and caesarean delivery. Risk was highest when a crisis required delivery, but remained elevated when it resolved before delivery.

The study distinguishes the added risk associated with a recorded sickle cell crisis from sickle cell anaemia without a crisis in a very large population dataset. It reinforces the need for specialist pregnancy planning, rapid assessment and continued monitoring after an acute episode.

Peer-reviewed population-based retrospective cohort covering 2,698,556 Quebec pregnancies from 1989 to 2022

Mouse study links kidney iron with sickle-cell kidney injury

Researchers studied renal iron accumulation and kidney injury in humanized sickle-cell mice. Iron chelation reduced kidney iron and prevented declining kidney function and disease progression in male HbSS mice. It did not produce the same kidney protection in female HbSS mice. The treatment reduced a pro-inflammatory kidney signal but did not change the other tested injury pathways.

The study supports renal iron as one possible contributor to sickle-cell kidney damage and highlights a biological difference between male and female mice. It gives researchers a mechanism to investigate further, but it does not show that adding or changing iron-chelation treatment prevents kidney disease in people with sickle cell disease.

Peer-reviewed preclinical study in humanized HbSS mice

French lung-ultrasound study is recorded as completed

The ECHO-STA record changed from recruiting to completed. It now reports actual enrolment of 190 children rather than an estimated 150, and actual primary and final completion on 31 October 2022 rather than estimated dates in 2023. The four-centre French study compared repeated lung ultrasound with chest X-ray during hospital admission for a vaso-occlusive crisis.

The completed cohort is larger than originally estimated and could help assess whether bedside ultrasound detects lung changes linked to acute chest syndrome earlier or with less radiation than repeated chest X-rays. The registry update only confirms that data collection ended. It does not report diagnostic accuracy or clinical outcomes.

ClinicalTrials.gov prospective multicentre diagnostic-study registry update

Paediatric study finds different parvovirus B19 patterns by sickle-cell genotype

Researchers reviewed 98 children with sickle cell disease and parvovirus B19 infection between 2023 and 2025: 76 had HbSS or sickle beta-zero thalassaemia and 22 had HbSC. The HbSC group more often had back pain, higher inflammatory and cell-injury markers, more chest X-rays and longer inpatient stays. Among the HbSS or sickle beta-zero group, hydroxyurea treatment was associated with higher haemoglobin and fewer transfusions, but also more neutropenia.

Parvovirus B19 is best known for causing a sudden fall in red-cell production. This study suggests its presentation may differ by sickle-cell genotype and adds real-world evidence about how children already taking hydroxyurea fared during infection. It may help frame further clinical research, but it does not create a new treatment or care recommendation.

Peer-reviewed retrospective multicentre observational study

Longitudinal Saudi cohort describes a later stroke pattern

Researchers followed 195 people with HbSS or sickle beta-zero thalassaemia for a median 13.5 years, totalling 2,173 patient-years. Fourteen strokes occurred, 13 ischaemic and one haemorrhagic, for an overall incidence of 0.64 per 100 patient-years. No overt stroke occurred before age 10. By age 30, cumulative incidence was 5.0% for overt ischaemic stroke and 18.6% for silent cerebral infarction. Hydroxyurea use rose from 44% to 85% during follow-up.

The age pattern differs from the recognised childhood stroke peak in many HbSS populations. The authors suggest higher fetal haemoglobin, wider hydroxyurea use and supportive care may contribute, while leaving room for population-specific factors. The study helps describe long-term cerebrovascular risk in an underrepresented population rather than proving why the pattern differs.

Peer-reviewed longitudinal observational cohort study

UK study describes migrant parents acting as unpaid care navigators

Interviews with migrant parents of children and young people with sickle cell disease in England found that parents often coordinated care across healthcare, education and welfare systems without structured support. They described learning unfamiliar institutional rules, rebuilding disrupted support networks, managing stigma and repeatedly advocating for care despite valuing UK specialist expertise.

The study makes visible the practical and emotional work families do when services do not join up around them. Its main implication is a service-design question: whether condition-specific navigation support should be built into specialist care rather than leaving families to connect systems themselves.

Peer-reviewed qualitative interview study

SCD BioChip study completion estimate moves two years later

The SCD BioChip study remains recruiting at one Cleveland site with an estimated enrolment of 100 people aged 12 and over. Its estimated primary and final completion moved from 31 May 2028 to 31 May 2030. The study began in October 2014 and uses discarded clinical blood or tissue to investigate a microfluidic chip for cell adhesion and other blood-cell characteristics.

The two-year move means evidence from this long-running diagnostic-technology study is now expected later. Recording it prevents the previous 2028 estimate from being treated as current or as a likely results date.

ClinicalTrials.gov observational-study milestone change

Four Indian sites complete recruitment activity in paediatric etavopivat study

The latest HIBISCUS 3 record changes four Indian locations from recruiting to completed. One further Indian site remains not yet recruiting, while four sites in Nigeria and one in Oman remain recruiting. Overall study status is still recruiting. The study estimates 27 participants aged 12 to 16 and tests etavopivat alone or with stable hydroxyurea in young people with raised transcranial Doppler velocities.

The change suggests enrolment or study activity has finished at most listed Indian centres while recruitment continues elsewhere. It is progress in a study testing whether etavopivat changes a blood-flow measure used to identify stroke risk, but it is not evidence that the medicine prevents stroke.

ClinicalTrials.gov Phase 2 trial registry status change

Paediatric brain-light feasibility study delays estimated start to November

The PHOTOSCAN record moved its estimated start from August to November 2026 while remaining not yet recruiting. The planned 60-person study will randomise children aged 8 to 17 to active transcranial photobiomodulation or sham treatment. Its primary outcomes concern participation, acceptability, feasibility and side effects.

The delay moves the earliest likely recruitment window by about three months. The study is an exploratory test of whether delivering near-infrared light through the scalp is feasible and safe enough to study for cognitive and brain-oxygenation outcomes in children with sickle cell disease.

ClinicalTrials.gov randomised feasibility-trial milestone change

Small randomised music-therapy study records an actual start

The Atlanta study now records 1 September 2026 as its actual start and remains recruiting. It plans to randomise 25 people aged 8 to 18 to four weeks of daily 20-minute virtual music-therapy sessions or standard educational material, measuring pain, quality of life and exploratory immune-cell gene expression.

The update confirms that a small controlled study of a low-burden supportive intervention has started. Randomisation is useful, but the sample is intended to explore signals and mechanisms rather than provide a definitive answer about pain care.

ClinicalTrials.gov randomised supportive-care trial launch

Adult study links circulating immature red cells with a distinct sickle-cell phenotype

Researchers retrospectively analysed 270 adults with HbSS or sickle beta-zero thalassaemia during steady state. Circulating nucleated red blood cells were found in 65.6%. Their presence was associated with lower haemoglobin and laboratory patterns suggesting altered red-cell production, while a higher percentage was linked with several other blood measures.

The count is already obtainable from blood analysis and could become a practical marker for separating biologically different patient groups. The study identifies an association and a research direction, not a test that can yet predict complications or choose treatment.

Peer-reviewed retrospective observational biomarker study

Required Casgevy clinician safety-information survey begins earlier than planned

The HMA-EMA catalogue now records that the required survey started on 1 September 2026 rather than the planned 30 September date. It will assess whether healthcare professionals who counsel people about Casgevy understand and use the additional safety materials. The listed study countries are Germany, Italy and Spain.

This is part of the regulatory system for checking whether risk-minimisation information is reaching clinicians in practice. It monitors knowledge and use of safety materials, not whether Casgevy is effective or whether new adverse events have occurred.

HMA-EMA required post-authorisation study record

Nairobi clinic data add real-world evidence on hydroxyurea in a low-resource setting

Researchers analysed 2,206 visits by 328 people with HbSS at two clinics serving Nairobi informal settlements. Hydroxyurea use was associated with a 0.36 g/dL higher haemoglobin level and a lower adjusted infection hazard. The estimated reduction in vaso-occlusive-crisis hazard was uncertain because its confidence interval included no difference.

The study adds implementation evidence from a setting that is underrepresented in sickle-cell research. It supports the importance of access and adherence around an established medicine, while showing how difficult it is to separate treatment effects from real-world differences between patients.

Peer-reviewed two-clinic retrospective observational study

First patients receive genomically matched blood through England programme

UCLH reports that patients across England are now receiving transfusions selected using detailed genomic blood-group information. The NHS England and NHS Blood and Transplant programme is being rolled out to around 17,000 people with sickle cell disorder, 800 people with thalassaemia and around 300 people with other transfusion-dependent inherited anaemias.

The programme has moved beyond collecting and testing samples into using genomic results to select blood for transfusion. A fuller blood-group profile can reveal variants that conventional testing may miss and can support closer matching for people who need repeated transfusions.

NHS national service implementation report

Phase 3 lidocaine pain trial expands recruitment across France and Guadeloupe

The latest record for NCT07274254 lists all 12 locations in France and Guadeloupe as recruiting. In the preceding version, posted 13 July 2026, one of 11 locations was recruiting and the others were not yet recruiting. The trial plans to randomise 104 adults admitted to intensive care with severe vaso-occlusive crisis or acute chest syndrome to intravenous lidocaine plus standard care or placebo plus standard care.

This activates broader recruitment for a quadruple-masked Phase 3 test of whether lidocaine can reduce cumulative parenteral opioid use while also tracking pain, crisis resolution, complications, length of stay, quality of life and safety.

ClinicalTrials.gov Phase 3 randomised trial registry change

Cardiac iron-overload study moves completion estimates later

The NCT07023666 record moved estimated primary completion from 30 June 2026 to 30 June 2027 and final completion from 30 June 2027 to 30 December 2027. The recruiting 100-person study combines cardiac monitoring with iron-chelation treatment and tracks sickle-cell-related hospitalisation and cardiac outcomes.

The one-year shift means evidence from the study is likely to arrive later than previously expected. Tracking the revised date prevents an already-passed estimate from being mistaken for completed research or imminent results.

ClinicalTrials.gov registry milestone change

First peer-reviewed sickle-cell case reported for transformer base editing

A four-person Cell Stem Cell report included one 21-year-old Nigerian woman with HbSS and three people with transfusion-dependent beta thalassaemia. The treatment edits BCL11A binding sites in the HBG1 and HBG2 promoters to reactivate fetal haemoglobin. In the participant with sickle cell disease, total haemoglobin rose from 7.7 to 12.9 g/dL and fetal haemoglobin from 3.5% to 62.2% by month 3. No vaso-occlusive episodes were reported through 15.5 months, compared with more than four in the preceding year.

This is the first peer-reviewed clinical case reported for this transformer base-editing platform in sickle cell disease. It shows that the approach can edit and return a person's own blood stem cells and produce a strong fetal-haemoglobin response. It does not establish effectiveness across patients or justify calling the treatment a cure.

Peer-reviewed descriptive report from three early trials; one participant had sickle cell disease

Indian centre reports four years of automated red-cell exchange experience

A centre in Chhattisgarh reviewed 115 automated red-cell-exchange procedures in 50 people with HbSS presenting with acute vaso-occlusive crises. Mean HbS fell from 67.4% before exchange to 26.0% afterwards, below 30% in every session. Haemoglobin remained stable. During a median 18-month follow-up, the authors reported fewer annual crises, no new stroke or acute chest syndrome, and conservatively managed adverse events in 14.8% of procedures.

The study shows that a resource-intensive transfusion service can consistently reach its immediate HbS target at a high-burden centre in India. It adds practical evidence about delivering automated exchange outside the settings that dominate the published literature.

Peer-reviewed single-centre retrospective observational study

Laboratory study maps gene-expression differences linked with hydroxyurea treatment

Researchers grew erythroid cells from blood samples taken from hydroxyurea-treated and untreated patients with sickle cell disease and healthy controls. Bulk RNA sequencing found 1,398 differentially expressed genes in untreated sickle cell samples and 495 in treated samples compared with controls. Twelve selected genes were checked with a second laboratory method.

The work points to oxidative phosphorylation, proteasome, autophagy, immune and inflammatory pathways that may help explain disease biology or hydroxyurea response. These are hypotheses for further study, not new treatment targets ready for patients.

Peer-reviewed laboratory transcriptomic study using patient-derived cells

Sudanese study finds very high parasite burden, but no significant sickle-cell difference

At Kosti Teaching Hospital, stool testing found intestinal parasites in 86 of 100 children with sickle cell anaemia and 82 of 100 children without it. The difference was not statistically significant. Giardia intestinalis was reported in 62% of the sickle cell group, and infection was more frequent in children older than five.

The striking result is the high burden in both groups. It points towards sanitation, water and wider environmental exposure as public-health concerns rather than evidence that sickle cell status itself caused more infection in this sample.

Peer-reviewed single-hospital cross-sectional study

Review brings together evidence on racial discrimination and sickle-cell care

A Brazilian research team synthesised 11 articles concerning racial discrimination in sickle cell disease. The review describes links between institutional racism, racial bias, depression, how professionals understand the disease and how care is delivered.

It keeps discrimination and trust visible as clinical and service-quality issues, not separate social concerns. The review supports more equitable care and policy work, but it does not test a specific intervention.

Peer-reviewed integrative review of 11 articles

MHRA publishes a modified paediatric development plan for etavopivat

The MHRA accepted changes to Novo Nordisk's paediatric investigation plan and deferral for oral etavopivat in sickle cell disease. The plan covers mini-tablet development, a randomised efficacy and safety study in people aged 12 to under 18 and adults, an open-label safety and pharmacokinetic study from 6 months to under 18, and modelling to support paediatric dosing. Birth to under 6 months is waived. The plan completion date is 31 July 2029.

A paediatric investigation plan sets the studies and age-appropriate formulation work a developer must complete or defer as part of regulatory development. It shows that UK paediatric development remains active and now has a verified endpoint date.

MHRA decision on a paediatric investigation plan modification

Paediatric cohort compares three conditioning intensities before matched-sibling transplant

Researchers compared 50 busulfan-based myeloablative, 10 reduced-intensity and 31 nonmyeloablative HLA-identical transplants in children and adolescents. The nonmyeloablative group used less pain-control support, parenteral nutrition, transfusion and hospital care, and none met the combined acute grade 2 to 4 or chronic graft-versus-host disease endpoint, compared with 20% after myeloablative and 30% after reduced-intensity conditioning. Four deaths occurred in the myeloablative group. Eight patients in the reduced or nonmyeloablative groups needed a second transplant for declining donor chimerism.

Conditioning toxicity is a major part of transplant burden. These results support further study of a lower-intensity approach that may reduce immediate toxicity and preserve ovarian reserve while still controlling sickle cell disease.

Peer-reviewed single-centre mixed retrospective and prospective cohort

Large US study finds recent opioid dispensing widened without broad dose escalation

Researchers analysed 48,760 people with sickle cell disease in US commercial and Medicaid claims. From 2021 to 2023, total dispensing increased for all six studied opioids in Medicaid and for oxycodone and morphine in commercial insurance. Mean days supplied and mean daily morphine-equivalent dose did not significantly increase for any opioid and insurance combination.

The pattern is more consistent with prescriptions reaching a wider share of people than with broadly more intense regimens among existing recipients. That matters after years of concern that general opioid restrictions can unintentionally reduce access to sickle-cell pain treatment.

Peer-reviewed retrospective insurance-claims cohort

Long-read study reveals overlooked beta-globin variation in African participants

Researchers analysed the beta-globin region in 40 people with sickle cell disease, predominantly recruited from three African countries. Using the more complete T2T-CHM13 reference reduced structural-variant calls by 70% compared with hg38 and identified 343 structural variants and 196 single-nucleotide variants not previously reported. A common insertion overlapping the HBB promoter appeared among people with high fetal haemoglobin.

Reference genomes and databases underrepresent African variation even though sickle cell burden is highest in Africa. Better mapping of the beta-globin region may improve future research into disease severity, fetal haemoglobin and gene-based therapies.

Peer-reviewed targeted long-read genomic study

Review links sickle cell disease with poorer school outcomes in lower-resource countries

A systematic review included 11 studies involving 1,630 participants in low- and middle-income countries. Seven studies reported poorer academic performance among children with sickle cell disease than comparison groups, and several reported more grade repetition. Older age and school absence were among the factors most often associated with poorer outcomes.

The review brings scattered education findings together and makes the effect of illness on school participation more visible. It supports further study of practical educational support alongside clinical care, particularly where children face both disease burden and limited resources.

Peer-reviewed systematic review with narrative synthesis

Review finds climate data is still rarely integrated into sickle-cell prediction models

Researchers reviewed 34 machine-learning studies published from 2005 to 2026 that addressed sickle-cell crises or mortality. Temperature, humidity, rainfall, wind, air quality and seasonal patterns appeared in some work, but most models relied mainly on clinical and demographic information and high-burden regions were underrepresented.

Combining personal health information with local weather and air-quality data could eventually support earlier warnings or service planning. The review identifies what would be needed next: longitudinal datasets, stronger climate integration, multicentre validation and more research in high-burden settings.

Peer-reviewed systematic review

Exploratory study tests MRI as a non-invasive marker of marrow recovery after transplant

Researchers measured MRI proton density fat fraction after organ-sparing total marrow irradiation and bone-marrow transplantation. The study included 10 control and eight treated sickle-cell mice, plus longitudinal scans in two adults with severe sickle cell disease. MRI values increased after transplant in both adults, and the study reports a one-year biopsy showing marrow recovery without fibrosis.

A repeatable scan could potentially monitor marrow recovery without relying only on invasive biopsy. This study establishes a technically plausible signal to test in a larger human cohort, not a clinically ready biomarker.

Peer-reviewed preclinical study with two-person human feasibility component

Baghdad study will compare video and game-based sickle-cell education

The University of Baghdad registered a planned 120-person randomised study with three groups: a short AI-generated educational video, an educational game and no intervention. The outcome assessor is masked. Self-care agency and self-efficacy will be measured before, immediately after and one month after the intervention.

The study could help distinguish whether short digital education formats improve confidence and reported self-management in adolescents. Including an active format comparison may be more informative than evaluating one educational resource alone.

New randomised supportive-care trial registry record

Kinshasa study finds frequent proximal kidney-tubule dysfunction in adults

Researchers measured urinary alpha-1 microglobulin in 246 adults with stable sickle cell disease in Kinshasa. Using the study's threshold, 48% had evidence of proximal tubular dysfunction. Recent vaso-occlusive crises, leg ulcers and albuminuria were independently associated with elevated levels, while hydroxyurea use was associated with lower odds.

Kidney damage in sickle cell disease is often discussed through albumin leakage and filtration. This study adds evidence that injury to the kidney's proximal tubules may also be common and that urinary alpha-1 microglobulin deserves prospective study as a marker.

Peer-reviewed multicentre cross-sectional study

Phase 1 study will test buccal buprenorphine during acute sickle-cell pain care

Boston Children's Hospital registered a 25-person, open-label dose-escalation safety study for people aged 12 to 22 admitted with acute sickle-cell pain. Participants will receive one buccal dose of buprenorphine while transitioning from hydromorphone patient-controlled analgesia. The registry estimates an October 2026 start and October 2031 primary completion.

The study asks whether a partial opioid agonist can be introduced safely during an acute admission and reduce reliance on full opioid agonists. Its primary outcome is a 48-hour safety measure, with pain, opioid consumption and satisfaction as secondary outcomes.

New Phase 1 clinical-trial registry record

Ain Shams University registers an ongoing sickle-cell cohort in Cairo

Ain Shams University newly posted a ClinicalTrials.gov record for an institutional cohort that began on 17 March 2024. It aims to assemble clinical, complication, treatment and quality-of-life data for 400 children and young adults with sickle cell disease. Primary completion is estimated for 1 January 2027.

A structured local registry can make disease patterns and care gaps more visible in Egypt and support later service planning or research. Its value will depend on completeness, consistent definitions and whether findings are published.

New observational registry record

Acute-chest ultrasound feasibility study marked complete

NCT06880679 changed from recruiting to completed with 27 actual participants. The single-group study assessed the feasibility and acceptability of point-of-care lung ultrasound during admission for suspected acute chest syndrome. The registry now gives 6 May 2026 as the actual primary and final completion date.

Lung ultrasound could offer a bedside, radiation-free complement to chest X-ray if later results establish reliable detection and useful clinical decisions.

ClinicalTrials.gov registry status change

Small MitoQ supplement study marked complete without posted results

NCT04109820 changed from recruiting to completed with 18 actual participants. The non-randomised study compared short-term MitoQ exposure in people with sickle cell anaemia and controls, measuring platelet activation and reactive oxygen species. The record retrospectively lists primary completion on 27 September 2022 and final completion on 30 June 2025.

The completed study may eventually add human evidence about a mitochondria-targeted antioxidant mechanism. At present, the update only confirms that data collection ended.

ClinicalTrials.gov registry status change

Plerixafor stem-cell mobilisation pilot completion estimate moves to July 2027

NCT03664830 remains active, not recruiting, with five actual participants. Its estimated primary and final completion dates moved from 3 August 2026 to 6 July 2027.

Plerixafor is used to move blood-forming stem cells into the bloodstream for collection. Safe, adequate collection is a practical part of autologous gene-therapy pathways, so a substantial follow-up delay matters even without a new efficacy result.

ClinicalTrials.gov registry milestone change

Randomised ketamine pain trial moves its estimated start to 10 September

The planned start of NCT07369024 moved from 1 April to 10 September 2026. The Phase 2 study plans to randomise 120 people aged 5 to 20 to standard opioid care plus low-dose intravenous ketamine or standard care plus placebo, with opioid requirement as the primary outcome.

The triple-masked design could produce more useful evidence about whether low-dose ketamine reduces opioid need during acute vaso-occlusive pain than uncontrolled treatment reports.

ClinicalTrials.gov registry milestone change

Proof-of-concept urine assay detects existing proteinuria in adults with sickle cell disease

Researchers compared a proprietary non-albumin urinary-protein immunoassay with albumin-to-creatinine ratio testing in 147 adults: 50 controls, 48 people with sickle cell disease without proteinuria and 49 with proteinuria. Both measures separated the existing proteinuric group from the other groups, while their values were only moderately correlated.

The assay may be detecting a different mixture of urinary proteins from standard albumin testing. That creates a testable route toward finding kidney injury that albumin-only tests could miss, but this study did not establish that advantage.

Peer-reviewed case-control proof-of-concept study

Reduced-intensity transplant trial moves from suspended to active follow-up

ClinicalTrials.gov changed NCT04362293 from suspended to active, not recruiting. The record now reports 46 actual participants, actual primary completion on 16 June 2026 and estimated final completion in August 2029. The previous version said enrolment was held because of recent serious adverse events.

The study is again recorded as continuing follow-up after a long suspension. It tests lower-intensity matched-sibling and haploidentical transplantation in children and young adults, where reducing conditioning toxicity could widen curative options if safety and disease-free survival are acceptable.

ClinicalTrials.gov registry status change

Randomised stress and pain self-management app trial marked complete

NCT04484272 is now marked completed with 239 actual participants. The randomised study compared outcome self-monitoring with the same monitoring plus relaxation, distraction and support delivered through the You Cope, We Support mobile intervention. The registry gives an actual primary completion date of 2 March 2026 and study completion date of 13 March 2026.

This is a relatively large completed behavioural trial focused on pain, stress and opioid use in adults with sickle cell disease. Its eventual results could show whether a supported mobile intervention adds benefit beyond symptom tracking alone.

ClinicalTrials.gov registry status change

Randomised smartphone mindfulness study registered for pain and sleep

The REMedy_RCT study plans to randomise 48 adolescents and young adults to an eight-week smartphone mindfulness programme or usual care. The primary outcome is pain interference at eight weeks, with secondary measures including pain intensity, sleep disturbance, fatigue, anxiety and depression.

It will test a low-burden supportive-care approach for two linked problems that can reinforce each other: pain and disrupted sleep. Randomisation should provide more useful evidence than an uncontrolled app evaluation.

New ClinicalTrials.gov registry record

Review questions routine macrolide use for paediatric acute chest syndrome

The review says vaccination has reduced bacterial infection risk, while recent respiratory-panel studies found most paediatric acute chest syndrome cases were associated with viruses and atypical bacteria were uncommon. The authors propose ceftriaxone alone as empiric antibiotic treatment, adding azithromycin only when a panel detects Mycoplasma pneumoniae or Chlamydia pneumoniae.

If confirmed and adopted, a test-guided approach could reduce unnecessary macrolide exposure while preserving initial bacterial cover. It challenges pathways that routinely combine a cephalosporin with a macrolide.

Peer-reviewed narrative review / expert opinion

Casgevy final and long-term evidence enters EMA regulatory procedure

The EMA PRAC agenda confirms that Vertex Pharmaceuticals (Ireland) Limited submitted final results from CTX001-121 in severe sickle cell disease, final CTX001-111 results in transfusion-dependent beta thalassaemia and interim CTX001-131 long-term follow-up results. The submission supports proposed updates to Casgevy safety and efficacy sections, the patient leaflet and risk-management plan. The procedure, EMA/VR/0000356719, was listed for adoption at the 31 August to 3 September PRAC meeting.

This closes the earlier uncertainty about whether the required evidence was submitted. It moves the evidence from a due-date watch into formal regulatory consideration, but it does not reveal the detailed results or create a new treatment decision by itself.

Regulatory obligation

Small Indian trial reports an early haemoglobin signal for desidustat

Twenty-four adults were studied for eight weeks. A haemoglobin response of at least 1 g/dL occurred in 50% of the six people assigned to the highest-dose cohort, compared with 16.7% of six placebo recipients.

It is a human randomized signal for an oral mechanism that increases the body's own erythropoietin response. It is not evidence of a cure or proof that crises are prevented.

Phase IIa randomized trial

Vertex reports a UK Casgevy submission for children aged 5 to 11

Vertex said it had completed a UK regulatory submission seeking Casgevy use in children aged 5 to 11.

If accepted and approved, the eligible age range could widen. A company filing is not an approval and does not create NHS access.

Company announcement

US Casgevy indication expands to children aged 2 years and older

The FDA expanded Casgevy's US indication to people aged 2 years and older with sickle cell disease and recurrent vaso-occlusive crises.

This is the first Casgevy approval covering very young children, but eligibility still involves intensive stem-cell collection and conditioning treatment.

Regulatory decision

Tessera reports in vivo HBB editing in long-term stem cells of non-human primates

At ASGCT 2026, Tessera reported that a single intravenous dose of an RNA Gene Writer in targeted lipid nanoparticles reached long-term blood-forming stem cells in non-human primates. Single-cell analysis found that an average of 85% of the analysed cells contained at least one edited HBB allele. The programme uses target-primed reverse transcription and is designed to correct the sickle-causing HBB mutation directly without a DNA double-strand break.

This combines two ambitious changes to the current gene-editing process: correcting HBB rather than reactivating fetal haemoglobin, and performing the edit inside the body rather than collecting and modifying stem cells in a laboratory. If it translates safely to people, it could avoid stem-cell mobilisation, myeloablative conditioning and transplantation and make treatment easier to deliver globally.

Company-sponsored non-human-primate data presented in a conference abstract

WHO issues its first global sickle-cell guideline for children and adolescents

WHO issued 15 recommendations covering diagnosis, infection prevention, hydroxyurea, pain, acute chest syndrome, stroke prevention and complication screening for people aged 0 to 19.

It closes a major global guidance gap and is designed for implementation in resource-limited settings as well as specialist care.

WHO normative guideline / GRADE

Base-edited risto-cel produces a strong early fetal-haemoglobin signal

Thirty-one people received risto-cel, an ex-vivo base-edited autologous stem-cell therapy. At six months, mean fetal haemoglobin exceeded 60% among 13 people with data; no investigator-reported severe crises occurred after the post-transfusion window.

It is the clearest published human signal yet for base editing in sickle cell, a different platform from Casgevy's CRISPR-Cas9 nuclease editing.

Phase 1/2 single-group interim analysis

Cas12a-edited reni-cel normalises mean haemoglobin in a small early study

Twenty-eight people received reni-cel. At six months, 18 people with available data had mean total haemoglobin of 13.8 g/dL and mean fetal haemoglobin of 48.1%; 27 of 28 had no severe post-infusion vaso-occlusive event.

This is human evidence for Cas12a editing of the HBG1/HBG2 promoters, distinct from both Casgevy and base-edited risto-cel.

Phase 1/2 single-group unplanned analysis

UK Parliament maps treatment progress against persistent access barriers

The Parliamentary Office of Science and Technology published a synthesis of established care, gene editing, service pressures and adoption barriers for sickle cell and beta thalassaemia.

It gives policymakers a shared evidence baseline and places scientific advances beside workforce, affordability and delivery constraints.

Parliamentary evidence briefing

National Haemoglobinopathy Panel reports on England's specialist network

The 2024/25 report brought together panel activity, novel-therapy pathway work, newborn outcomes, registry activity and coordinating-centre updates.

It makes the delivery infrastructure around specialist sickle-cell care and advanced therapies more visible nationally.

National service report

Traditional-medicine review finds signals, but not evidence ready for clinical claims

A review found 27 studies: 11 laboratory, four animal, six clinical and six qualitative. Some formulations showed preliminary signals, but products, methods and endpoints varied substantially.

It provides a structured map of traditional-medicine research while showing why laboratory anti-sickling activity should not be presented as proven patient benefit.

Peer-reviewed scoping review

WHO publishes its first global guidance for sickle cell in pregnancy

WHO issued recommendations covering pregnancy, childbirth and the interpregnancy period for women living with sickle cell disease.

It creates a global evidence framework for a population facing substantially higher maternal and pregnancy risk.

WHO normative guideline

England commits £9 million to expand automated red-cell exchange

The funding was allocated to expand Spectra Optia capacity, specialist centres, out-of-hours provision and the workforce supporting automated red-cell exchange.

This targets a treatment already important to many people with sickle cell and may reduce travel and uneven access between regions.

Government and NHS funding announcement

Small gene-therapy study tests reduced-intensity conditioning

Seven people received lentiviral gene therapy after reduced-intensity melphalan rather than conventional myeloablative busulfan; all showed sustained modified fetal haemoglobin and more than 80% fewer severe crises over reported follow-up.

Reducing conditioning toxicity is one of the most important routes to making gene therapy safer and accessible to more people.

Phase 1/2 single-group trial

Phase 3 STAND trial does not confirm crizanlizumab efficacy

Among 252 participants, neither tested dose significantly reduced the annualised rate of crises leading to healthcare visits compared with placebo.

It formally documents the confirmatory failure that had already driven European revocation of Adakveo and cautions against relying on the earlier positive study alone.

Phase 3 randomised placebo-controlled trial

Seven English sites pilot emergency-department bypass for uncomplicated crises

The Rare Diseases Action Plan reported seven mobilised pilots intended to route uncomplicated vaso-occlusive crises toward faster pain relief and specialist care, alongside work on accessible digital care plans.

It directly targets delays and poor acute-care experiences rather than introducing another medicine.

Government policy and implementation report

Casgevy enters managed NHS access for eligible people in England

NICE recommended exagamglogene autotemcel through managed access for some people aged 12 and over with severe sickle cell disease, recurrent crises and no matched related stem-cell donor.

Eligible patients can be considered while further evidence is collected. Treatment includes stem-cell collection, laboratory gene editing, conditioning chemotherapy and reinfusion.

NICE guidance / managed access

NHS England standardises stem-cell mobilisation for Casgevy candidates

NHS England defined clinical criteria for using plerixafor to mobilise blood stem cells in eligible people proceeding toward exagamglogene autotemcel treatment.

It turns a technically important preparation step into a standardised commissioned pathway, helping centres collect enough stem cells for manufacture and backup.

NHS specialised commissioning policy

UK sickle-cell BioResource opens recruitment to children

The Improving Black Health Outcomes BioResource opened sickle-cell recruitment to children aged 0 to 15 at seven NHS trusts.

Including children expands the genomic and health-data resource available for research into disease mechanisms, variation and future treatments.

NIHR research recruitment update

PIVOT provides rare randomised evidence for hydroxyurea in HbSC

Among 212 children and adults with HbSC, dose-limiting toxicities occurred in 33% on hydroxyurea and 11% on placebo, so the primary safety non-inferiority endpoint was missed. Pain and hospitalisation rates nevertheless favoured hydroxyurea.

HbSC has been underrepresented in trials. The clinical signals justify a larger confirmatory study, but the missed primary endpoint prevents a simple positive verdict.

Phase 2 randomised trial

Oral mitapivat raises haemoglobin in a phase 2 sickle-cell trial

RISE UP randomised 79 people to mitapivat 50 mg, 100 mg or placebo for 12 weeks and reported a haemoglobin-response signal for the oral red-cell pyruvate-kinase activator.

It supports a non-gene-therapy route aimed at improving red-cell energy and haemolytic anaemia, but patient-important benefits require larger and longer testing.

Phase 2 randomised placebo-controlled trial

All UK Oxbryta batches recalled after new safety findings

The MHRA instructed pharmacies and wholesalers to stop supplying and quarantine all Oxbryta 500 mg tablets after emerging trial data suggested an unfavourable balance of vaso-occlusive crises and fatal events.

This was an urgent reversal in the availability of voxelotor and a reminder that improving a laboratory marker does not guarantee better clinical outcomes.

MHRA medicines recall

Genomics England launches a Black-health research resource centred on sickle cell

The Improving Black Health Outcomes BioResource began recruiting adults with and without sickle cell disease, combining health information, samples and an optional National Genomic Research Library contribution.

It addresses chronic underrepresentation in genomic research and creates infrastructure for studying why disease and treatment responses vary.

National research-platform announcement

Cochrane finds antioxidant supplement evidence too uncertain for firm conclusions

Cochrane assessed trials of vitamins C and E, zinc, N-acetylcysteine, L-arginine and omega-3. Most outcomes were supported by low- or very-low-certainty evidence, with no firm overall benefit established.

It is a useful corrective to confident supplement claims: biologic plausibility and small studies are not enough to establish meaningful benefit.

Cochrane systematic review

Pivotal exa-cel study reports sustained freedom from severe crises

Of 44 treated participants, 30 had enough follow-up for the primary endpoint: 29 of 30 had no severe vaso-occlusive crisis for at least 12 consecutive months, and all 30 had no hospitalisation for a severe crisis over that interval.

These were the central clinical data behind Casgevy's breakthrough, showing durable crisis control in the evaluable group rather than relying only on haemoglobin markers.

Peer-reviewed phase 3 single-group trial

European Commission grants Casgevy conditional authorisation

Casgevy received EU conditional authorisation for eligible people aged 12 and over with severe sickle cell disease where stem-cell transplantation is appropriate but no matched related donor is available.

This moved the first CRISPR-based treatment from trial evidence into European regulation, with continuing evidence obligations attached.

European regulatory record

NHS launches expanded blood-group genotyping for inherited anaemias

A new NHS test began offering detailed blood-group genotyping to nearly 18,000 eligible people with sickle cell, thalassaemia and other inherited anaemias.

More precise matching can help transfusion services find compatible blood and reduce the risk of immune reactions in people who may need repeated transfusions.

NHS service implementation

FDA approves the first two gene therapies for sickle cell disease

The FDA approved Casgevy, which uses CRISPR/Cas9 editing, and Lyfgenia, which uses a lentiviral vector. Lyfgenia's label carried a boxed warning for haematological malignancy.

The decisions established two distinct one-time genetic treatment routes and made their different mechanisms and risk profiles clinically important.

FDA regulatory decision

UK authorises the world's first CRISPR-based medicine

The MHRA authorised Casgevy for eligible people aged 12 and over with severe sickle cell disease and recurrent vaso-occlusive crises where transplantation was appropriate but no matched related donor was available.

It was the first regulatory authorisation anywhere for a medicine using CRISPR gene editing and the starting point for later UK access decisions.

MHRA regulatory decision