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Sickle Cell Disease Treatments Compared

Name: Sickle Cell Disease Treatments Compared
Creator: Jason Hunter
Published: 2026-10-01

5 FDA-approved drugs and 1 in development, side by side from the current prescribing labels. Newest label Jul 2026. Checked October 1, 2026.

One-time gene therapiesCasgevy · Lyfgenia

Daily oralDroxia (also Siklos) · Endari

Monthly infusionAdakveo

Five treatments are FDA-approved for sickle cell disease, and they are 2 different kinds of thing. Casgevy and Lyfgenia, both approved December 8, 2023, are one-time gene therapies given in a transplant hospital after high-dose chemotherapy; in their trials 29 of 31 Casgevy patients had no severe pain crises for at least 12 months in a row and 28 of 32 Lyfgenia patients had no vaso-occlusive events between months 6 and 18. Hydroxyurea, a daily capsule or tablet approved for sickle cell in 1998, cut painful crises from 4.6 to 2.5 a year against placebo. Adakveo is a monthly clinic infusion whose label now says its confirmatory trial did not establish benefit, and Endari is an oral powder twice a day that cut crises by about 25%. Mitapivat, a twice-daily pill, has an FDA decision date of November 1, 2026.

Side by side

5 approved sickle cell disease treatments at a glance

How each drug is given, how often, who it is approved for and when it was first approved, from the current FDA label.

Sickle Cell Disease treatments compared: route, schedule, approved use and approval date
Drug	How it is given	How often	Approved for	First approved
Casgevy exagamglogene autotemcel Vertex Pharmaceuticals / CRISPR Therapeutics	One-time IV infusion of your own CRISPR-edited stem cells, given in a transplant hospital after high-dose busulfan chemotherapy; stem cells are collected weeks earlier	one-time	People 2 and older with sickle cell disease and recurrent vaso-occlusive crises	December 8, 2023
Lyfgenia lovotibeglogene autotemcel Genetix Biotherapeutics (formerly bluebird bio)	One-time IV infusion of your own gene-modified stem cells, given in a transplant hospital after high-dose busulfan chemotherapy; stem cells are collected weeks earlierAbout 30 minutes per dose	one-time	People 12 and older with sickle cell disease and a history of vaso-occlusive events	December 8, 2023
Droxia (also Siklos) hydroxyurea Waylis Therapeutics (Droxia); Medunik (Siklos); generics also sold	Capsule (Droxia) or tablet (Siklos) by mouth once a day	Once daily; start 15 mg/kg (20 mg/kg for children on Siklos), raise by 5 mg/kg every 8 to 12 weeks to a max of 35 mg/kg/day; blood counts every 2 weeks	Sickle cell anemia with recurrent moderate to severe painful crises; Siklos covers ages 2 and older	February 25, 1998
Adakveo crizanlizumab-tmca Novartis	IV infusion at a clinic over 30 minutesAbout 30 minutes per dose	5 mg/kg at week 0 and week 2, then every 4 weeks; can be used with or without hydroxyurea	Adults and children 16 and older with sickle cell disease, to reduce vaso-occlusive crises	November 15, 2019
Endari L-glutamine oral powder Emmaus Medical	Powder mixed into a drink or soft food, by mouth twice a day	5 g, 10 g or 15 g twice daily by body weight (1 to 3 packets per dose)	Adults and children 5 and older with sickle cell disease, to reduce acute complications	July 7, 2017

The calendar

A year on each sickle cell disease treatment

Every dose in a year, drawn to the label schedule, so the difference between a daily pill and a twice-yearly infusion is the picture.

Casgevy

One-time gene therapy, at a clinic

Given once

Lyfgenia

One-time gene therapy, at a clinic

Given once

Droxia (also Siklos)

By mouth, at home

365 doses a year

Adakveo

Infusion, at a clinic

13 doses a year

Endari

Other, at home

730 doses a year

Counts follow the label schedule for a full year on the maintenance dose. Drugs given in cycles or adjusted to blood tests have no fixed count, so their schedule is written out instead.

The evidence

What the pivotal sickle cell disease trials showed

The primary result from the trial each FDA approval rests on, as reported on the label.

Sickle Cell Disease pivotal trial results by drug
Drug	Pivotal trial	Primary result
Casgevy exagamglogene autotemcel Vertex Pharmaceuticals / CRISPR Therapeutics	Trial 1 (NCT03745287), 44 treated aged 12 and older, 31 evaluable; plus Trial 4, 11 children aged 5 to 11 Trial record or paper	29 of 31 evaluable patients (93.5%) had no severe VOCs for at least 12 months in a row; all 8 evaluable children aged 5 to 11 did too
Lyfgenia lovotibeglogene autotemcel Genetix Biotherapeutics (formerly bluebird bio)	Study 1-C (NCT02140554), Phase 1/2, 36 treated, 32 evaluable for VOE outcomes Trial record or paper	28 of 32 (88%) had no vaso-occlusive events between months 6 and 18 after infusion; 30 of 32 (94%) had no severe VOEs
Droxia (also Siklos) hydroxyurea Waylis Therapeutics (Droxia); Medunik (Siklos); generics also sold	MSH (Multicenter Study of Hydroxyurea in Sickle Cell Anemia), 299 adults	Median 2.5 painful crises a year vs 4.6 on placebo (46% fewer); crises needing hospital care 1.0 vs 2.5 a year
Adakveo crizanlizumab-tmca Novartis	SUSTAIN (NCT01895361), 198 people; 67 on the approved dose vs 65 on placebo Trial record or paper	Median 1.63 VOCs a year vs 2.98 on placebo (p=0.010); 36% had no VOC vs 17%
Endari L-glutamine oral powder Emmaus Medical	Phase 3 (NCT01179217), 230 people aged 5 to 58 Trial record or paper	Median 3 sickle cell crises over 48 weeks vs 4 on placebo; hospital stays for pain 2 vs 3; about 25% fewer crises overall (rate ratio 0.75)

Safety

Sickle Cell Disease treatment side effects and warnings

Lyfgenia and Droxia (also Siklos) carry a boxed warning, the FDA's strongest. The rest list their main precautions.

Sickle Cell Disease treatments: most common side effects and key warnings from the FDA labels
Drug	Most common side effects	Key warning
Casgevy exagamglogene autotemcel Vertex Pharmaceuticals / CRISPR Therapeutics	mouth sores (mucositis) 86%, fever with low white cells 48% and decreased appetite 41%	No boxed warning. Engraftment failure, delayed platelet recovery with bleeding risk, allergic reactions, and possible off-target gene edits.
Lyfgenia lovotibeglogene autotemcel Genetix Biotherapeutics (formerly bluebird bio)	mouth sores (stomatitis) 71%, low platelets 69% and low neutrophils 60%	Boxed warning Boxed warning: blood cancer (hematologic malignancy) has occurred in treated patients; lifelong monitoring with blood counts at least every 6 months.
Droxia (also Siklos) hydroxyurea Waylis Therapeutics (Droxia); Medunik (Siklos); generics also sold	infections 43%, headache 20% and dry skin 12%	Boxed warning Boxed warning: severe bone marrow suppression (low blood counts) and cancer risk; hydroxyurea is carcinogenic.
Adakveo crizanlizumab-tmca Novartis	joint pain 18%, nausea 18% and back pain 15%	No boxed warning. Infusion-related reactions, some needing hospital care; interference with automated platelet counts.
Endari L-glutamine oral powder Emmaus Medical	constipation 21%, nausea 19% and headache 18%	No boxed warning. The label has no Warnings and Precautions section.

Not yet approved

Sickle cell disease treatments in Phase 3 or under FDA review

Investigational drugs with a Phase 3 trial, shown separately because their results are not from a label. Status as of the date in each row.

Sickle Cell Disease drugs in development
Drug	Status	How it works and is given	Pivotal trial	Result so far	What is next
mitapivat (Pyrukynd / Aqvesme) Agios Pharmaceuticals	Under FDA reviewas of October 1, 2026	Oral pyruvate kinase activator that boosts red blood cell energy and lowers hemolysisPill by mouth twice a day (100 mg)	RISE UP, Phase 2/3 (NCT05031780); 207 people aged 16 and older in the Phase 3 part, 2:1 to mitapivat or placeboPrimary endpoint: Two primary endpoints: hemoglobin response (rise of at least 1 g/dL, weeks 24 to 52) and annualized rate of sickle cell pain crises ClinicalTrials.gov	Met hemoglobin response: 40.6% vs 2.9% on placebo (p<0.0001). Did not meet pain crises: 2.62 vs 3.05 a year (p=0.12). Fatigue endpoint also not met (Agios press release, 2025-11-19)	FDA decision (PDUFA date) November 1, 2026; filed for accelerated approval with priority review (Agios, 2026-07-07) Agios press release, July 7, 2026 (PDUFA date); Agios press release, Nov 19, 2025 (RISE UP topline results)

Cost

Help paying for sickle cell disease treatment

Drugmaker copay and free-drug programs, plus charity funds for the condition, checked every week.

Questions

Sickle Cell Disease treatment questions people ask

What is the difference between Casgevy and Lyfgenia?

Both are one-time gene therapies made from your own stem cells and given after busulfan chemotherapy, approved the same day in December 2023. In their trials, 29 of 31 Casgevy patients (94%) had no severe crises for at least 12 consecutive months, and 28 of 32 Lyfgenia patients (88%) had no vaso-occlusive events between months 6 and 18. Lyfgenia carries a boxed warning for blood cancer; Casgevy does not. Casgevy is approved from age 2 and Lyfgenia from age 12.

Does hydroxyurea still work for sickle cell disease?

Yes. Hydroxyurea is the longest-used sickle cell drug, with placebo-controlled evidence on crisis rates: in the MSH trial, adults had a median 2.5 painful crises a year against 4.6 on placebo, and crises needing hospital care fell from 2.5 to 1.0 a year. It is sold as Droxia capsules, Siklos tablets for age 2 and up, and generics.

Is Adakveo still recommended?

Adakveo (crizanlizumab) remains FDA-approved, but its June 2026 label says the confirmatory STAND trial did not establish efficacy, with 2.49 crises a year on Adakveo against 2.30 on placebo, and tells doctors to reassess whether to continue it each year. Its original approval rested on SUSTAIN, where crises fell from 2.98 to 1.63 a year.

Is mitapivat approved for sickle cell disease?

Not as of October 2026. Mitapivat is approved for other anemias and has an FDA decision date of November 1, 2026 for sickle cell disease. In its Phase 3 trial, 40.6% had a hemoglobin response against 2.9% on placebo, but the pain crisis endpoint was not met, 2.62 against 3.05 crises a year.

Go deeper

More on Sickle Cell Disease at Trial Friend

Sources

Where every number on this page comes from

Approved-drug facts are from the current FDA prescribing information on DailyMed, with the label's effective date. Investigational-drug facts are from ClinicalTrials.gov and the sources named in each row.

Casgevy (exagamglogene autotemcel) prescribing information, Vertex Pharmaceuticals / CRISPR Therapeutics, label dated Jul 2026. DailyMed. Pivotal trial: ClinicalTrials.gov
Lyfgenia (lovotibeglogene autotemcel) prescribing information, Genetix Biotherapeutics (formerly bluebird bio), label dated Jul 2026. DailyMed. Pivotal trial: ClinicalTrials.gov
Droxia (also Siklos) (hydroxyurea) prescribing information, Waylis Therapeutics (Droxia); Medunik (Siklos); generics also sold, label dated Sep 2025. DailyMed
Adakveo (crizanlizumab-tmca) prescribing information, Novartis, label dated Jun 2026. DailyMed. Pivotal trial: ClinicalTrials.gov
Endari (L-glutamine oral powder) prescribing information, Emmaus Medical, label dated Jun 2025. DailyMed. Pivotal trial: ClinicalTrials.gov
mitapivat (Pyrukynd / Aqvesme), Agios Pharmaceuticals: ClinicalTrials.gov record; Agios press release, July 7, 2026 (PDUFA date); Agios press release, Nov 19, 2025 (RISE UP topline results). Checked October 1, 2026.

This page compares what the FDA labels and pivotal trials report. It is not medical advice, and no trial on this page compared these drugs with each other. Written and checked by Jason Hunter; the method is on the editorial standards page.