Table 4.

Novel medications for β-thalassemia

Medication	Mechanism of action	Route and frequency of administration	Phase of development	Current target patient population	In development for sickle cell disease?	Comments
Luspatercept1,5	TGF-β inhibitor	Subcutaneous, every 3 weeks	EMA and FDA approved	NTDT, TDT	No	Full data for NTDT pending; in use for MDS
Sotatercept36,37	TGF-β inhibitor	Subcutaneous, every 3 weeks	Development halted	NTDT, TDT	No	In development for pulmonary hypertension
Sirolimus25-28	mTOR inhibitor; HbF induction	Oral, daily	Phase 2 trials	TDT	No	In use for other disorders
Benserazide31,32	HbF induction	Oral, daily	Phase 1 trial	NTDT	Yes	In use for Parkinson disease
IMR-68729,30	PDE-9 inhibitor; HbF induction	Oral, daily	Phase 2 trial	NTDT, TDT	Yes
Apotransferrin19-21	Hepcidin upregulation	Intravenous, every 2 weeks	Phase 2 trial	NTDT	No
VIT-276322	Ferroportin inhibitor	Oral, one or twice daily	Phase 2 trial	NTDT	Yes
PTG-30023	Hepcidin mimetic	Subcutaneous, once weekly	Phase 2 trials	NTDT, TDT	No	In development for hemochromatosis and polycythemia vera
Mitapivat33-35	Pyruvate kinase activator	Oral, twice daily	Phase 3 trials	NTDT, TDT	Yes	In development for pyruvate kinase deficiency
Ruxolitinib38	JAK 1/2 inhibitor	Oral, twice daily	Development halted	TDT	No	Spleen size reduction; no change in transfusion

EMA, European Medicines Agency; FDA, Food and Drug Administration; JAK, Janus-associated kinase; MDS, myelodysplastic syndrome; mTOR, mechanistic target of rapamycin.