Latanoprostene bunod ophthalmic solution 0.024% in the treatment of open-angle glaucoma: design, development, and place in therapy

Figures & data

Table 1 Clinical trials involving LBN

Study	Study phase	Study design	Study subjects	Number of subjects	Treatment	Length of treatment	Main outcome measure	Efficacy results
KRONUS^Citation16	I	Single-center, open-label	Healthy Japanese Males ≥20 years	24	LBN 0.024%	14 days	IOP reduction	– IOP was reduced from 13.6 (1.3) mm Hg at baseline to 10.0 (1.0) mm Hg
VOYAGER^Citation17	II	Randomized, controlled, multicenter, investigator- masked, dose-ranging	Subjects ≥18 years with OAG or OHT with baseline IOP ≥24 mm Hg	413	LBN 0.006%, LBN 0.012%, LBN 0.024%, LBN 0.040% or latanoprost 0.005%	28 days	Diurnal IOP reduction	– LBN’s IOP lowering was dose dependent with the maximum seen with LBN 0.024% – IOP lowering with LBN 0.024% was greater than with latanoprost 0.005% on day 28 (−9.00 mm Hg with LBN vs −7.77 mm Hg with latanoprost)
CONSTELLATION^Citation18	II	Randomized, single-center, controlled, open-label, crossover	Subjects 40–90 years old with OAG or OHT in one or both eyes	25	LBN 0.024%, timolol 0.5%	8 weeks total (crossover at 4 weeks)	Diurnal and nocturnal IOP reduction; ocular perfusion pressure	– LBN reduced IOP by 3.5 (0.24) mm Hg – Timolol reduced IOP by 1.7 (0.25) mm Hg – No significant different in diurnal IOP reduction between the two treatments, but LBN had greater nocturnal IOP reduction as compared to timolol (P=0.004) – LBN had improved diurnal ocular perfusion pressure vs baseline (P≤0.006) and improved nocturnal ocular perfusion pressure vs timolol (P=0.010)
APOLLO^Citation10	III	Randomized, multicenter, double-masked, parallel group	Subjects ≥18 years with OAG or OHT in one or both eyes	420	LBN 0.024%, Timolol 0.5%	3 months (with 9-month open-label safety extension phase)	IOP reduction	– LBN was noninferior to timolol – LBN 0.024% had significantly greater IOP reduction at all 9 time points assessed as compared to timolol (P≤0.002) (range 17.8–18.7 mm Hg with LBN vs 19.1–19.8 mm Hg with timolol)
LUNAR^Citation19	III	Randomized, multicenter, double-masked, parallel group	Subjects ≥18 years with OAG or OHT in one or both eyes	414	LBN 0.024%, timolol 0.5%	3 months (with 3-month open- label safety extension phase)	IOP reduction	– LBN 0.024% showed greater IOP reduction than timolol at all time points in the study except for at 8 am on week 2 (range 17.7–18.7 mm Hg with LBN vs 18.8–19.6 mm Hg with timolol)
JUPITER^Citation20	III	Multicenter, single-arm, open-label	Japanese subjects aged ≥20 years with OAG or OHT in one or both eyes	130	LBN 0.024%	52 weeks	IOP reduction	– 22% reduction in IOP (from 19.6 [2.9] at baseline to 15.3 [3.0]) was achieved by week 4 – IOP reductions maintained through week 52 (P<0.001 vs baseline at all visits)

Abbreviations: LBN, Latanoprostene bunod; OAG, open-angle glaucoma; OHT, ocular hypertension.

Table 2 Safety and tolerability of LBN 0.024%

Study (number of subjects treated with LBN 0.024%)	Ocular TEAEs	Number of subjects (%)	Nonocular TEAEs potentially related to treatment (number of subjects)	Study discontinuations (number of subjects)
KRONUS^Citation16 (24)	Conjunctival hyperemia Punctate keratitis Unspecified conjunctival disorder Eye pain Reduced visual acuity	12 (50) 13 (54) 1 (4) 1 (4) 1 (4)	None of the nonocular TEAEs were considered related to the study drug	None
VOYAGER^Citation17 (83) **Data included from LBN 0.024% group only	Instillation site pain Conjunctival hyperemia Punctate keratitis Ocular hyperemia Eye irritation Dry eye Photophobia	10 (12) 4 (4.8) 2 (2.4) 2 (2.4) 3 (3.6) 2 (2.4) 2 (2.4)	Headache (1)	1
CONSTELLATION^Citation18 (25)	Punctate keratitis Instillation site erythema	1 (4) 1 (4)	Nausea (1) Hyperhidrosis (1)	4
APOLLO^Citation10 (283)	Eye irritation Conjunctival hyperemia Eye pain Dry eye Foreign body sensation in eyes Instillation site pain	31 (11) 11 (3.9) 8 (2.8) 3 (1.1) 3 (1.1) 3 (1.1)	Headache (2) Fatigue (1) Sinus congestion (1) Hair disorder (1)	2
LUNAR^Citation19 (277)	Conjunctival hyperemia Eye irritation Eye pain Ocular hyperemia Vision blurred Eye pruritus Dry eye Punctate keratitis Foreign body sensation in eyes Instillation site pain	25 (9) 20 (7.2) 16 (5.8) 7 (2.5) 5 (1.8) 4 (1.4) 3 (1.1) 3 (1.1) 3 (1.1) 4 (1.4)	Madarosis (1) Chest discomfort (1) Dysgeusia (1) Headache (1) Insomnia (1) Dyspnea (1)	4
JUPITER^Citation20 (130)	Conjunctival hyperemia Growth of eyelashes Eye irritation Eye pain Iris hyperpigmentation Blepharal pigmentation Blepharitis Eye pruritus Asthenopia Conjunctival hemorrhage Punctate keratitis Trichiasis Cataract Hordeolum Foreign body sensation in eyes Visual impairment Vitreous floaters	23 (17.7) 21 (16.2) 15 (11.5) 13 (10) 5 (3.8) 4 (3.1) 3 (2.3) 3 (2.3) 3 (2.3) 2 (1.5) 3 (2.3) 3 (2.3) 1 (0.8) 1 (0.8) 2 (1.5) 1 (0.8) 1 (0.8)	None of the nonocular TEAEs were considered related to the study drug	4

Note: Data has only been included from the LBN 0.024% group since the table is discussing the safety and tolerability of LBN 0.024%.

Abbreviations: LBN, Latanoprostene bunod; TEAE, treatment-emergent adverse events.

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