Sickle Cell Disease — Global Competitive Landscape Report 2026 | EHA 2026

Sickle Cell Disease is included as an EHA 2026 disease-area keyword under non-malignant hematology, with relevant subtypes including Sickle Cell Pain Crises, Vaso-Occlusive Crises. This row helps turn conference abstracts into disease-focused SEO article clusters and makes it easier to connect drugs, targets, and trials to marketable content angles.

This competitive landscape analysis was generated using AI-powered research workflows in Eureka LS, which integrates patent data, literature, and molecular insights into a structured report in minutes.

Executive Summary

Sickle cell disease (SCD) is the most prevalent inherited hemoglobinopathy worldwide. The single point mutation in HBB (Glu6Val) produces hemoglobin S, which polymerizes under deoxygenated conditions and rigidifies erythrocytes. People living with SCD experience recurrent vaso-occlusive crises, chronic hemolytic anemia, and organ damage. The disease burden falls disproportionately on populations of African ancestry and on under-resourced health systems globally.

Notably, the Patsnap Eureka pharma-intelligence stack returns 276 drug records tagged to sickle cell disease, 781 sickle cell-related patent families filed since January 2023, and 360 active Phase 2 or Phase 3 trials. Within that pool, two FDA-approved one-time gene therapies anchor the curative arm: exagamglogene autotemcel (Casgevy, Vertex / CRISPR Therapeutics, 2023-12-08, the first approved CRISPR/Cas9 therapy in any disease) and lovotibeglogene autotemcel (Lyfgenia, bluebird bio, 2023-12-08, lentiviral gene addition). Disease-modifying small molecules and biologics include hydroxyurea (legacy), L-glutamine (Endari, 2017), voxelotor (Oxbryta, 2019, withdrawn 2024), crizanlizumab-tmca (Adakveo, 2019, EU withdrawn 2023), and mitapivat (Pyrukynd, 2022, expanded Phase 3 in SCD).

As a result, EHA 2026 frames SCD across three converging strategic axes. The gene therapy arm cements one-time curative intent for severe disease. The pyruvate kinase activator class (mitapivat, etavopivat) tests whether a small-molecule daily oral can deepen hemoglobin and reduce vaso-occlusive crisis frequency. Voxelotor’s 2024 voluntary withdrawal and Adakveo’s EU pullback reframe what counts as durable benefit in this population. The strategic question is which architecture serves which patient subset as access economics, payer scrutiny, and post-approval real-world data converge.

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Traditionally, compiling this level of analysis would require weeks of manual research across platforms like Google Patents and PubMed. With Eureka LS, the same process can be automated — from extracting molecules to mapping competitive pipelines — into a structured output like the report below.

Arena Overview

Sickle cell disease biology snapshot — Hemoglobin S (HbS) results from a Glu6Val substitution in the β-globin chain. Under low oxygen tension HbS polymerizes, distorts erythrocytes into the rigid sickle shape, and triggers vaso-occlusion plus hemolysis. As a result, therapy spans four mechanism families: HbS polymerization inhibitors (voxelotor), red cell metabolism enhancers (mitapivat, etavopivat — pyruvate kinase activators), anti-adhesion/anti-inflammatory agents (crizanlizumab P-selectin mAb, hydroxyurea, L-glutamine), and one-time curative gene therapies (CRISPR-edited HSC, lentiviral β-globin addition).

SCD pipeline (276 records) — Among SCD-tagged drug records, six architectural classes compete: gene therapies (exagamglogene autotemcel CRISPR/Cas9, lovotibeglogene autotemcel lentiviral, betibeglogene autotemcel earlier-generation), pyruvate kinase activators (mitapivat, etavopivat), HbS polymerization inhibitors (voxelotor — withdrawn), anti-adhesion biologics (crizanlizumab-tmca, inclacumab), small molecules (hydroxyurea, L-glutamine, IMR-687, GBT021601), and supportive care including iron chelators (deferasirox), HSC mobilization agents (motixafortide, plerixafor), and hematopoietic stem cell therapies (omidubicel, dorcobeligene autotemcel).

SCD patent activity (since 2023) — In addition, assignees have filed 781 sickle cell-related patent families since January 2023. The filings span next-generation gene-editing approaches (base editing, prime editing, in vivo lipid-nanoparticle delivery), pyruvate kinase activators with deeper PKM2 selectivity, fetal hemoglobin (HbF) inducers, P-selectin and E-selectin biologics, and pediatric formulations of approved disease-modifying agents.

Player Summary Table

Player	Region	Tier	Primary Route	Key Evidence
Vertex Pharmaceuticals / CRISPR Therapeutics	US/CH	T1 (Curative leader)	CRISPR/Cas9 gene editing (BCL11A enhancer)	Exagamglogene autotemcel (Casgevy, 2023-12-08); first FDA-approved CRISPR therapy in any disease
bluebird bio	US	T1 (Curative)	Lentiviral β-globin gene addition	Lovotibeglogene autotemcel (Lyfgenia, 2023-12-08); BB305 vector with βA-T87Q
Agios Pharmaceuticals	US	T1 (PK activator)	Pyruvate kinase activator (small molecule)	Mitapivat (Pyrukynd, 2022 PK deficiency); RISE UP Phase 3 in SCD; ENERGIZE in thalassemia
Novo Nordisk (Forma Therapeutics)	DK/US	T1 (PK activator challenger)	PKR activator	Etavopivat — Phase 3 HIBISCUS in SCD; oral once-daily
Pfizer (Global Blood Therapeutics legacy)	US	T2 (HbS inhibitor)	HbS polymerization inhibitor	Voxelotor (Oxbryta, 2019); voluntary 2024 withdrawal due to vaso-occlusive crisis and mortality imbalance signal
Novartis (Adakveo)	CH	T2 (Anti-adhesion)	P-selectin monoclonal antibody	Crizanlizumab-tmca (2019-11-15); EU marketing authorization withdrawn 2023; US label retained
Bristol Myers Squibb (Endari, with Emmaus)	US	T2 (Small molecule)	L-glutamine	L-glutamine oral powder (2017); reduces VOC frequency; pediatric ≥5

Next-generation Gene Editing, Anti-adhesion, and Standard of Care

Player	Region	Tier	Primary Route	Key Evidence
Editas Medicine	US	T2 (Gene editing challenger)	CRISPR/Cas12a HBG1/2 promoter editing	Reni-cel (EDIT-301) — Phase 1/2 RUBY trial; HbF reactivation alternative to BCL11A approach
Beam Therapeutics	US	T2 (Base editor)	Adenine base editor (HBG1/2 promoter)	BEAM-101 — Phase 1/2 BEACON trial; precise base-editing without double-strand breaks
Sangamo Therapeutics / Sanofi (legacy)	US/FR	T3 (Zinc finger)	Zinc-finger nuclease BCL11A editing	BIVV003 — discontinued; early ZFN approach to sickle cell gene editing
Pfizer (Inclacumab)	US	T3 (P-selectin mAb)	Long-acting P-selectin mAb	Inclacumab — Phase 3 in vaso-occlusive crisis prevention; quarterly dosing
Imara / Cyclerion (legacy)	US	Watchlist (PDE9)	PDE9 inhibitor	IMR-687 — Phase 2 stalled; tovinontrine PDE9 program in SCD
Tetraphase / Bristol Myers Squibb (legacy hydroxyurea)	Global	T1 (Standard of care)	Ribonucleotide reductase inhibitor	Hydroxyurea (Hydrea / Droxia / Siklos); foundational disease-modifying therapy
BioMarin / Endari licensee network	Global	T3 (Generics)	Generic L-glutamine, hydroxyurea	Pediatric formulations; global access programs
Multiple academic CRISPR / base editing programs	US/EU	Watchlist	In vivo gene editing	Lipid nanoparticle in vivo HBG1/2 base editing programs in preclinical-Phase 1; bypasses HSC harvest and conditioning

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Route Differentiation Analysis

In particular, six therapeutic routes define the modern SCD competitive landscape. Each strength level draws from MCP pipeline records and the published trial evidence.

Route × Player Matrix

Player	One-time Gene Therapy	Pyruvate Kinase Activator	Anti-adhesion Biologic	HbS Polymerization Inhibitor	HbF Inducer / Standard of Care
Vertex / CRISPR Therapeutics	Strong — Casgevy (CRISPR/Cas9 BCL11A)	Absent	Absent	Absent	Absent
bluebird bio	Strong — Lyfgenia (lentiviral βA-T87Q)	Absent	Absent	Absent	Absent
Editas Medicine	Strong — Reni-cel (Cas12a HBG1/2)	Absent	Absent	Absent	Absent
Beam Therapeutics	Moderate — BEAM-101 (base editor)	Absent	Absent	Absent	Absent
Agios Pharmaceuticals	Absent	Strong — Mitapivat (RISE UP Phase 3)	Absent	Absent	Absent
Novo Nordisk (Forma)	Absent	Strong — Etavopivat (HIBISCUS Phase 3)	Absent	Absent	Absent
Novartis	Absent	Absent	Strong — Crizanlizumab (Adakveo, EU withdrawn 2023)	Absent	Absent
Pfizer (GBT legacy)	Absent	Absent	Emerging — Inclacumab Phase 3	Voxelotor — withdrawn 2024	Absent
BMS / Emmaus (Endari)	Absent	Absent	Absent	Absent	Strong — L-glutamine (2017)
Generic / SoC manufacturers	Absent	Absent	Absent	Absent	Strong — Hydroxyurea global standard
Sangamo / Sanofi (legacy)	Discontinued — BIVV003 ZFN	Absent	Absent	Absent	Absent
Imara / Cyclerion (legacy)	Absent	Absent	Absent	Absent	Watchlist — IMR-687 PDE9 inhibitor stalled
Academic in vivo gene editing	Emerging — LNP HBG1/2 base editing	Absent	Absent	Absent	Absent

Route Concentration Observations

• One-time gene therapy — Additionally, two FDA-approved gene therapies sit at the top of the curative-intent pyramid. Casgevy and Lyfgenia approved on the same day in 2023-12. Editas’s reni-cel and Beam’s BEAM-101 take the next-generation HbF reactivation through base editing.
• Pyruvate kinase activator — Meanwhile, Agios’s mitapivat and Novo Nordisk’s etavopivat compete head-on through Phase 3 trials (RISE UP, HIBISCUS) for the daily-oral SCD market. The mechanism enhances red cell ATP generation and reduces sickling indirectly.
• Anti-adhesion biologic — In contrast, crizanlizumab (Novartis Adakveo) lost EU marketing authorization in 2023 after STAND Phase 3 failed. Pfizer’s inclacumab moves into the same category with quarterly dosing but faces uphill scientific scrutiny.
• HbS polymerization inhibitor — Similarly, voxelotor (Pfizer’s Oxbryta from the GBT acquisition) was voluntarily withdrawn in 2024 after post-marketing data showed vaso-occlusive crisis and mortality imbalance. The category lost its only approved asset.
• HbF inducer / standard of care — Furthermore, hydroxyurea remains the global foundational therapy and now anchors combinations with mitapivat or pyruvate kinase activators. L-glutamine adds an oxidative-stress-reduction layer with pediatric utility.

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Top Player Deep Dives

1. Vertex Pharmaceuticals / CRISPR Therapeutics — Casgevy (Tier 1 — Curative leader)

Primary route: CRISPR/Cas9 ex vivo gene-edited autologous hematopoietic stem cell therapy targeting the BCL11A erythroid enhancer to reactivate fetal hemoglobin (HbF).

Key product: Exagamglogene autotemcel (Casgevy, exa-cel) — FDA approval 2023-12-08 for severe SCD; same-day MHRA UK approval. EMA approval followed in 2024-02. The first CRISPR/Cas9-edited therapy approved in any disease.

Pivotal trials: CLIMB-121 (sickle cell disease) and CLIMB-111 (transfusion-dependent β-thalassemia). Long-term follow-up in CLIMB-131 demonstrates durable VOC freedom in most treated participants.

Differentiation: Notably, Casgevy edits the BCL11A erythroid enhancer to derepress γ-globin, raising HbF and out-competing HbS polymerization. As a result, the curative effect comes from a single conditioning + infusion procedure rather than chronic dosing.

Trajectory: Moreover, Vertex/CRISPR Therapeutics now focus on access economics — list price $2.2M and the 4-6 month vein-to-vein conditioning timeline limit broad community use. Pediatric expansion and ex-US payer agreements drive 2026 volume.

Key risk: However, busulfan myeloablative conditioning carries fertility, secondary malignancy, and procedural mortality risk. Editas, Beam, and academic in vivo LNP base-editing programs aim to remove HSC harvest and conditioning entirely.

SCD Approved + Late-stage Asset Snapshot

Asset	Architecture	Sponsor	FDA Approval	Setting
Hydroxyurea	Ribonucleotide reductase inhibitor	Multiple generic	1998 (SCD label)	Standard of care; HbF inducer
L-glutamine (Endari)	Amino acid; redox modulator	BMS / Emmaus	2017-07-07	VOC reduction; pediatric ≥5
Voxelotor (Oxbryta)	HbS polymerization inhibitor	Pfizer (ex-GBT)	2019; withdrawn 2024-09	Voluntary withdrawal — VOC and mortality imbalance
Crizanlizumab (Adakveo)	P-selectin mAb	Novartis	2019-11-15; EU withdrawn 2023	VOC frequency reduction; US label retained
Casgevy (exa-cel)	CRISPR/Cas9 BCL11A enhancer edit	Vertex / CRISPR Therapeutics	2023-12-08	Severe SCD; one-time curative
Lyfgenia (lovo-cel)	Lentiviral βA-T87Q gene addition	bluebird bio	2023-12-08	Severe SCD; one-time curative

2. bluebird bio — Lyfgenia (Tier 1 — Lentiviral curative)

Primary route: Lentiviral β-globin gene addition through autologous hematopoietic stem cell modification.

Key product: Lovotibeglogene autotemcel (Lyfgenia) — FDA approval 2023-12-08 for severe SCD with history of vaso-occlusive events. Uses the BB305 lentiviral vector encoding βA-T87Q, an anti-sickling β-globin variant.

Differentiation: Specifically, lovo-cel adds an anti-sickling β-globin allele directly rather than relying on HbF reactivation. As a result, durable HbS reduction and VOC freedom occur within months of infusion.

Trajectory: In addition, bluebird now navigates the post-approval commercial pivot — list price $3.1M and a hematologic malignancy black box warning constrain uptake. The company’s restructuring places SCD revenue under intense scrutiny.

Key risk: However, AML cases observed in earlier lentiviral SCD trials drove the FDA black box warning. Long-term safety data versus Casgevy will determine eventual market share split.

3. Agios Pharmaceuticals — Mitapivat (Tier 1 — PK activator leader)

Primary route: Allosteric activator of pyruvate kinase R (PKR) in red blood cells.

Key product: Mitapivat (Pyrukynd) — FDA approval 2022-02-17 for adults with pyruvate kinase deficiency; Phase 3 RISE UP in SCD; ENERGIZE Phase 3 in non-transfusion-dependent β-thalassemia.

Differentiation: Notably, mitapivat enhances red cell ATP and 2,3-DPG metabolism, which reduces HbS polymerization indirectly. As a result, an oral once-daily small molecule could deepen hemoglobin and reduce VOC frequency without conditioning.

Trajectory: Furthermore, Agios positions mitapivat as the daily-oral disease-modifying therapy for the broader SCD population that gene therapy cannot reach economically. Pediatric expansion (ACTIVATE-Kids in PK deficiency) supports cross-indication evidence base.

Key risk: However, etavopivat (Novo Nordisk / Forma) competes head-on with the same mechanism. Hormonal and reproductive safety signals from PKR class effects need long-term real-world confirmation.

4. Novo Nordisk — Etavopivat (Tier 1 — PK activator challenger)

Primary route: Allosteric activator of pyruvate kinase R, acquired via the 2022 Forma Therapeutics acquisition.

Key product: Etavopivat — Phase 3 HIBISCUS in SCD. Once-daily oral.

Differentiation: Specifically, Novo Nordisk brings global commercial reach in chronic-disease markets and a PKR activator with potentially differentiated PK and tolerability versus mitapivat.

Trajectory: Moreover, HIBISCUS Phase 3 readout will define whether SCD becomes a multi-asset pyruvate kinase activator class or stays a single-vendor category.

Key risk: However, Novo Nordisk’s strategic pivot toward obesity and cardiometabolic indications may compress commercial focus on hematology launches. Etavopivat reads out into a market already shaped by mitapivat.

5. Pfizer — Voxelotor Withdrawal & Inclacumab (Tier 2 — Restructuring portfolio)

Primary route: HbS polymerization inhibitor (voxelotor) and long-acting P-selectin monoclonal antibody (inclacumab).

Key products: Voxelotor (Oxbryta, 2019) — voluntarily withdrawn 2024-09 after post-marketing data showed VOC and mortality imbalance. Inclacumab — Phase 3 quarterly-dosed P-selectin mAb in development.

Differentiation: In particular, Pfizer acquired Global Blood Therapeutics in 2022 for $5.4B to enter SCD. Voxelotor’s withdrawal forces Pfizer to pivot the SCD franchise to inclacumab and to next-generation HbS modifiers (GBT021601).

Trajectory: Furthermore, Pfizer keeps the Pittsburgh GBT site running and continues investing in non-malignant hematology. Inclacumab’s quarterly dosing differentiates it from monthly crizanlizumab.

Key risk: However, the voxelotor withdrawal damaged credibility in the hemoglobinopathy class. Real-world evidence and post-marketing diligence around any successor will face heightened scrutiny.

6. Editas + Beam — Next-generation Gene Editing (Tier 2 — Curative challengers)

Primary route: CRISPR/Cas12a (Editas) and adenine base editor (Beam) targeting the HBG1/2 promoter to reactivate fetal hemoglobin without double-strand breaks.

Key products: Reni-cel (EDIT-301, Editas Medicine) — Phase 1/2 RUBY trial. BEAM-101 (Beam Therapeutics) — Phase 1/2 BEACON trial.

Differentiation: Notably, both editors avoid the BCL11A enhancer edit used by Casgevy and instead reactivate γ-globin through HBG1/2 promoter modification. As a result, the editing footprint is smaller and arguably more precise.

Trajectory: Specifically, the next-generation race targets in vivo lipid-nanoparticle delivery that bypasses HSC harvest and busulfan conditioning. If successful, this could expand gene-editing therapy beyond academic cell-therapy centers.

Key risk: However, both reni-cel and BEAM-101 trail Casgevy by years. Long-term editing fidelity and off-target effects in HBG1/2 still require Phase 3-scale safety data.

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BD Deals & Strategic Moves

Key business development activity shaping the sickle cell disease competitive landscape:

Date	Deal	Parties	Type	Significance
2017-07	L-glutamine (Endari) FDA approval	BMS / Emmaus Life Sciences	Regulatory	First new SCD therapy in 20 years; pediatric ≥5 utility
2019-11	Crizanlizumab (Adakveo) + Voxelotor (Oxbryta) FDA approvals	Novartis + Global Blood Therapeutics	Regulatory	Two new disease-modifying mechanisms approved within weeks
2022-02	Mitapivat (Pyrukynd) FDA approval (PK deficiency)	Agios Pharmaceuticals	Regulatory	Pyruvate kinase activator class established; SCD development pathway opened
2022-08	Pfizer acquires Global Blood Therapeutics	Pfizer + GBT	M&A ($5.4B)	Brought voxelotor into Pfizer hematology; SCD franchise entry
2022-09	Novo Nordisk acquires Forma Therapeutics	Novo Nordisk + Forma	M&A ($1.1B)	Brought etavopivat (PKR activator) into Novo Nordisk SCD pipeline
2023-12	Casgevy + Lyfgenia FDA approvals (same day)	Vertex / CRISPR Therapeutics + bluebird bio	Regulatory	First two gene therapies approved for SCD; first CRISPR therapy in any disease
2023-09	Crizanlizumab EU marketing authorization withdrawn	Novartis	Regulatory pullback	STAND Phase 3 confirmed lack of VOC reduction; reframes anti-adhesion mechanism
2024-09	Voxelotor (Oxbryta) voluntary withdrawal	Pfizer	Regulatory	Post-marketing VOC and mortality imbalance signal; HbS polymerization inhibitor class loses anchor
2024-2026	RISE UP (mitapivat) + HIBISCUS (etavopivat) Phase 3 readouts	Agios + Novo Nordisk	Pivotal trials	Define whether daily-oral PKR activators reach SCD label
2024-2026	RUBY (reni-cel) + BEACON (BEAM-101) Phase 1/2	Editas Medicine + Beam Therapeutics	Clinical milestones	Next-generation HbF reactivation strategies challenge Casgevy and Lyfgenia

Strategic Pattern

Strategic pattern: Overall, the SCD BD theme is the simultaneous emergence of curative one-time gene therapies and a robust daily-oral disease-modifying class. Vertex and bluebird now own the curative arm; Agios and Novo Nordisk fight for the chronic oral market. Pfizer’s Oxbryta withdrawal and Novartis’s Adakveo EU pullback reframe what counts as benefit. Generic hydroxyurea remains the global access foundation, while gene therapy access economics constrain commercial scale. The next two years decide patient sequencing and reimbursement architecture for each population segment.

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Unmet Needs & White Spaces

Notably, three white spaces meet all three criteria — sparse coverage, clear technical value, and a realistic entry path:

White Space	Current Coverage	Technical Value	Entry Path
In vivo gene editing without conditioning (LNP-delivered base editor or prime editor that bypasses HSC harvest and busulfan)	Sparse — preclinical-stage academic and biotech programs; Casgevy and Lyfgenia both require ex vivo manipulation + myeloablative conditioning	High — removes fertility, secondary malignancy, and procedural mortality risks; expands curative therapy beyond academic centers	Phase 1 of LNP-HBG1/2 base editor candidates; partnerships with Casgevy/Lyfgenia infrastructure for manufacturing transition
Pediatric SCD disease-modifying combinations (mitapivat + hydroxyurea or etavopivat + hydroxyurea pediatric protocols)	Sparse — current pediatric data limited to hydroxyurea, L-glutamine; PKR activators studied largely in adults	High — preventing organ damage in childhood is the highest-impact intervention window in SCD	Pediatric Phase 3 of mitapivat or etavopivat + hydroxyurea; cooperative-group trials with HMOs and Medicaid populations
Affordable global access for gene therapy (sub-$500K curative regimens through manufacturing or financing innovation)	Sparse — Casgevy and Lyfgenia priced $2-3M; SCD prevalence concentrated in low- and middle-income countries that cannot afford current price	High — solves the disease-burden distribution mismatch where the most affected populations cannot access curative therapy	Outcome-based payment models, manufacturing localization to Africa/India, philanthropic and ex-US payer partnerships, in vivo platforms

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Risks and Strategic Outlook for 2026 and Beyond

Key Risks

1. Voxelotor and crizanlizumab post-approval risk: However, two recent withdrawals or pullbacks (voxelotor 2024, Adakveo EU 2023) raise the bar for any new SCD therapy. Phase 3 efficacy on hard endpoints (VOC frequency, transfusion need, mortality) is now mandatory, not surrogate hemoglobin gain.
2. Gene therapy access economics: Moreover, $2-3M list prices and 4-6 month vein-to-vein timelines limit Casgevy and Lyfgenia uptake even in well-resourced markets. The disease-burden mismatch with low- and middle-income geography compounds the access problem.
3. PKR activator hormonal signal: Notably, mitapivat and etavopivat both carry potential hormonal and reproductive concerns from PKR activation in non-erythroid tissues. Long-term real-world data will determine pediatric and reproductive-age use.
4. Lyfgenia AML black box warning: Furthermore, hematologic malignancy cases observed in earlier lentiviral SCD trials drove the FDA black box warning. Long-term safety follow-up will determine market share split versus Casgevy.

Strategic Outlook

For strategic planning, the safest near-term bet around SCD is combination expansion of hydroxyurea + PKR activator — pairing the foundational standard of care with mitapivat or etavopivat to capture the broad daily-oral disease-modifying market. However, the highest-upside, highest-risk bets are in in vivo gene editing that removes the conditioning barrier and in affordable global access models that solve the disease-burden distribution mismatch. White-space opportunities exist in pediatric disease-modifying combinations, in next-generation HbF inducers (HBG1/2 base editing), and in cooperative-group post-approval real-world data programs that establish durable benefit beyond the trial setting. The next two years of SCD economics will depend less on which gene therapy wins and more on whether the chronic oral and the curative one-time arms can together cover the global burden in a sustainable way.

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