Elinzanetant: a phase III therapy for postmenopausal patients with vasomotor symptoms

Figures & data

Figure 1. Schematic of the links between KNDy neurons, the regulation of GnRH secretion, and the vasomotor area in the hypothalamus.

Figure 2. Daily frequency of: moderate and severe hot flashes (a), severity of hot flashes (b), daily hot flash severity score (c), and waking at night due to night sweats (d), by day. Data shown are mean ± standard error (severity score = [number of mild hot flashes x 1] + [number of moderate hot flashes x 2] + [number of severe hot flashes x 3]). From [50] under CCBY-NC-ND.

Figure 3. Change from baseline in mean daily frequency (a, c) and weekly severity (b, d) of moderate and severe VMS by Treatment Group. Abbreviations: EZN, elinzanetant; LS, least square; SE, standard error. From [51] under CCBY-NC-ND.

Table 1. Most common adverse events (reported in ≥ 10% of subjects in any treatment group) in RELENT-1.

System Organ Class Preferred Term	Placebo N = 18 n (%)	Elinzanetant once-daily dose
		50 mg N = 15 n (%)	100 mg N = 15 n (%)	150 mg N = 15 n (%)	300 mg N = 13 n (%)
Any adverse event	13 (72.2)	7 (46.7)	11 (73.3)	10 (66.7)	11 (84.6)
Somnolence	3 (16.7)	5 (33.3)	2 (13.3)	5 (33.3)	9 (69.2)
Headache	3 (16.7)	0	5 (33.3)	1 (6.7)	6 (46.2)
Diarrhea	0	1 (6.7)	0	1 (6.7)	3 (23.1)
Pelvic pain	2 (11.1)	3 (20.0)	0	0	0
Dyspepsia	2 (11.1)	0	0	1 (6.7)	0
Alanine aminotransferase increased	0	0	2 (13.3)^a	0	0

^aAlanine aminotransferase (ALT) increased to 1.3 × upper limit of normal (ULN) on Day 8, decreasing to 1.1×ULN on Day 14 in one subject; and to 2.6 × ULN on Day 8, decreasing to 1.4 × ULN on Day 14 in the other subject. Four other subjects (2 receiving placebo and 2 receiving 300 mg NT-814) had similar changes in ALT that were not reported as adverse events.

From [50] under CCBY-NC-ND.

Table 2. Treatment-emergent adverse events by treatment group in SWITCH-1.

AE category	Placebo group, No. (%) (N = 47)	Elinzanetant group, No. (%)
		40 mg (n = 31)	80 mg (n = 17)	120 mg (n = 52)	160 mg (n = 52)	Total (N = 152)
Any TEAE	28 (60)	17 (55)	14 (82)	34 (65)	38 (73)	103 (67.8)
Serious TEAEs	2 (4)	0	1 (6)	1 (2)	1 (2)	3 (2.0)
TEAEs leading to discontinuation of study treatment	1 (2)	0	2 (12)	0	5 (10)	7 (4.6)
Most common TEAEs (occurring in ≥ 3 participants in any treatment group)
Headache	6 (13)	3 (10)	2 (12)	6 (12)	4 (8)	15 (9.9)
Somnolence	1 (2)	3 (10)	1 (6)	2 (4)	6 (12)	12 (7.9)
Dizziness	0	0	0	3 (6)	3 (6)	6 (3.9)
Nasopharyngitis	4 (9)	1 (3)	0	3 (6)	0	4 (2.6)
Diarrhea	3 (6)	2 (6)	2 (12)	3 (6)	3 (6)	10 (6.6)
Blood creatine phosphatase increased	1 (2)	1 (3)	1 (6)	3 (6)	1 (2)	6 (3.9)
Fatigue	0	3 (10)	1 (6)	1 (2)	4 (8)	9 (5.9)

Abbreviations: AE, adverse event; TEAE, treatment-emergent adverse event.

From [51] under CCBY-NC-ND.

Trower M, Anderson RA, Ballantyne E, et al. Effects of NT-814, a dual neurokinin 1 and 3 receptor antagonist, on vasomotor symptoms in postmenopausal women: a placebo-controlled, randomized trial. Menopause. 2020 Feb 17;27(5):498–505. doi: 10.1097/GME.0000000000001500

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Simon JA, Anderson RA, Ballantyne E, et al. Efficacy and safety of elinzanetant, a selective neurokinin-1,3 receptor antagonist for vasomotor symptoms: a dose-finding clinical trial (SWITCH-1). Menopause. 2023 Jan 31;30(3):239–46. doi: 10.1097/GME.0000000000002138

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