Table 1. Novel therapeutics for... | American Society of Hematology

Table 1.

Novel therapeutics for hemophilia

Product	Mechanism	Advantages			Limitations			Status
Product	Mechanism	Dosing frequency	Route	Relative ease of compliance	Immunogenicity	Monitoring	Study population	Status
EHL-rFVIII
Efmoroctocog alfa (BDD-rFVIII-Fc, Eloctate)⁷	IgG1-Fc fusion	Every 3-5 d	IV	Low	3% NNA	Standard	PTP	Approved
Rurioctacog alfa pegol (BAX 855, Adynovate)⁸	20-kDa pegylation	Twice weekly	IV	Low	4% NNA	Standard	PTP	Approved
Damoctocog alfa pegol (BAY 94-9027)⁴	60-kDa site-specific pegylation	Every 3-7 d	IV	Low	3% NNA0.6% anti-PEG	Chromogenic*	PTP	Phase 3
Turoctocog alfa pegol (N8-GP)⁵	40-kDa site-specific pegylation	Every 4 d	IV	Low	0.6% NNA	TBD	PTP	Phase 3
Turoctocog alfa pegol (N8-GP)⁵	40-kDa site-specific pegylation	Every 4 d	IV	Low	0.6% NAb†	TBD	PTP	Phase 3
EHL-rFIX
Eftrenonacog alfa (FIX-Fc, Alprolix)⁹	IgG1-Fc fusion	Every 7-10 d	IV	Medium	0.8% NNA	Standard*	PTP	Approved
Albutrepenonacog alfa (FIX-FP, Idelivion)¹⁰	Albumin fusion	Weekly to bimonthly	IV	Medium	0% NNA	Standard*	PTP	Approved
Nonacog β pegol (N9-GP, Rebinyn)¹³	40-kDa site-specific pegylation	Weekly	IV	Medium	4% NNA	Chromogenic*	On demand only in USA	Approved
NFTs
Emicizumab^30-32	Bispecific antibody FVIIIa-mimetic	Weekly	SQ	Medium	3% NNA	TBD	HA with inhibitor	Phase 3
Fitusiran^36,37	AT siRNA	Weekly to monthly	SQ	Medium	4% NNA	TBD	HA/HB without inhibitor	Phase 1/2
Concizumab³⁹	TFPI monoclonal antibody	TBD	IV/SQ	TBD	0%	TBD	HA/HB without inhibitor	Phase 1/2
Gene therapy
SPK-9001⁶⁰	Endogenous expression with AAV vectors	Vector dependent	IV	High	0%	Standard	HA/HB without inhibitor; no NAb to vector	Phase 1/2
AMT-060⁵⁷
BMN270⁵⁸

Product	Mechanism	Advantages			Limitations			Status
Product	Mechanism	Dosing frequency	Route	Relative ease of compliance	Immunogenicity	Monitoring	Study population	Status
EHL-rFVIII
Efmoroctocog alfa (BDD-rFVIII-Fc, Eloctate)⁷	IgG1-Fc fusion	Every 3-5 d	IV	Low	3% NNA	Standard	PTP	Approved
Rurioctacog alfa pegol (BAX 855, Adynovate)⁸	20-kDa pegylation	Twice weekly	IV	Low	4% NNA	Standard	PTP	Approved
Damoctocog alfa pegol (BAY 94-9027)⁴	60-kDa site-specific pegylation	Every 3-7 d	IV	Low	3% NNA0.6% anti-PEG	Chromogenic*	PTP	Phase 3
Turoctocog alfa pegol (N8-GP)⁵	40-kDa site-specific pegylation	Every 4 d	IV	Low	0.6% NNA	TBD	PTP	Phase 3
Turoctocog alfa pegol (N8-GP)⁵	40-kDa site-specific pegylation	Every 4 d	IV	Low	0.6% NAb†	TBD	PTP	Phase 3
EHL-rFIX
Eftrenonacog alfa (FIX-Fc, Alprolix)⁹	IgG1-Fc fusion	Every 7-10 d	IV	Medium	0.8% NNA	Standard*	PTP	Approved
Albutrepenonacog alfa (FIX-FP, Idelivion)¹⁰	Albumin fusion	Weekly to bimonthly	IV	Medium	0% NNA	Standard*	PTP	Approved
Nonacog β pegol (N9-GP, Rebinyn)¹³	40-kDa site-specific pegylation	Weekly	IV	Medium	4% NNA	Chromogenic*	On demand only in USA	Approved
NFTs
Emicizumab^30-32	Bispecific antibody FVIIIa-mimetic	Weekly	SQ	Medium	3% NNA	TBD	HA with inhibitor	Phase 3
Fitusiran^36,37	AT siRNA	Weekly to monthly	SQ	Medium	4% NNA	TBD	HA/HB without inhibitor	Phase 1/2
Concizumab³⁹	TFPI monoclonal antibody	TBD	IV/SQ	TBD	0%	TBD	HA/HB without inhibitor	Phase 1/2
Gene therapy
SPK-9001⁶⁰	Endogenous expression with AAV vectors	Vector dependent	IV	High	0%	Standard	HA/HB without inhibitor; no NAb to vector	Phase 1/2
AMT-060⁵⁷
BMN270⁵⁸

NAb, neutralizing antibodies; NNA, nonneutralizing antibodies; PTP, previously treated patients; SQ, subcutaneously; TBD, to be determined.

Differing results may be obtained with specific aPTT reagents; for detailed information on performance of standard vs chromogenic assays with these products, see Kitchen et al.⁷⁶

†

One patient developed inhibitor (initially low titer and then high at 13.5 BU) after 93 exposure days to N8-GP in phase 3 trial.

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