Latozinemab, a novel progranulin-elevating therapy for frontotemporal dementia

Kurnellas, Michael; Mitra, Ananya; Schwabe, Tina; Paul, Robert; Arrant, Andrew E.; Roberson, Erik D.; Ward, Michael; Yeh, Felix; Long, Hua; Rosenthal, Arnon

doi:10.1186/s12967-023-04251-y

Journal of Translational Medicine

Table 1 Summary of TEAEs (safety population)

From: Latozinemab, a novel progranulin-elevating therapy for frontotemporal dementia

	Double-blind, SAD HVs								Open-label
		Latozinemab dose level							aFTD-GRN 60 mg/kg (N = 6)
	Pooled placebo (n = 12)	2 mg/kg (n = 7)	6 mg/kg (n = 6)	15 mg/kg (n = 6)	30 mg/kg (n = 6)	60 mg/kg (n = 13)	Total AL001 (n = 38)	Total (N = 50)	aFTD-GRN 60 mg/kg (N = 6)
Any TEAE, n (%) [E]	8 (66.7)	2 (28.6)	5 (83.3)	4 (66.7)	5 (83.3)	8 (61.5)	24 (63.2)	32 (64.0) [70]	4 (66.7)
Any treatment-related TEAE, n (%) [E]	1 (8.3)^a	0 (0.0)	0 (0.0)	0 (0.0)	1 (16.7)^a	0 (0.0)	1 (2.6)	2 (4.0)	1 (16.7)^b
Severity of TEAEs, n (%) [E]
Mild	0 (0.0)	0 (0.0)	2 (33.3)	1 (16.7)	0 (0.0)	3 (23.1)	6 (15.8)	6 (12.0)	4 (66.7)
Moderate	7 (58.3)	2 (28.6)	3 (50.0)	3 (50.0)	5 (83.3)	4 (30.8)	17 (44.7)	24 (48.0)	0 (0.0)
Severe	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
Life-threatening	1 (8.3)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	1 (7.7)	1 (2.6)	2 (4.0)	0 (0.0)
Death	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
Severity of treatment-related TEAEs, n (%) [E]
Mild	1 (8.3)	0 (0.0)	0 (0.0)	0 (0.0)	1 (16.7)	0 (0.0)	1 (2.6)	2 (4.0)	1 (16.7)
Moderate	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
Severe	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
Life-threatening	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
Death	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
Any SAE, n (%) [E]	1 (8.3)^c	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	1 (7.7)^c	1 (2.6)	2 (4.0)	0 (0.0)
Any treatment-related SAE, n (%) [E]	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
Any TEAE leading to discontinuation, n (%) [E]	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
Any DLAE, n (%) [E]	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	NA

aFTD-GRN, asymptomatic carrier of GRN mutations causative of frontotemporal dementia; DLAE, dose-limiting adverse event; HV, healthy volunteer; SAD, single ascending dose; TEAE, treatment-emergent adverse event; SAE, serious adverse event
^a Post–lumbar puncture syndrome
^b Myalgia, lipase increased, and tachycardia
^c Rhabdomyolysis

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