Topical ocular laquinimod in development for inflammatory eye disorders
Purpose
Laquinimod (LAQ) is a first-in-class immunomodulator that activates the aryl-hydrocarbon receptor. Based on the preventive and inhibitory effects of LAQ on ocular inflammation observed in animal models1,2, it has therapeutic potential in uveitis. A pharmaceutical formulation optimised for ocular absorption of LAQ has been developed and its ocular tolerability confirmed in rabbit at 5-fold higher daily doses than in man (unpublished data). The present studies aimed at evaluating overall safety and ocular tolerability of topical ocular LAQ in man, and intra-ocular distribution of LAQ in rabbit.
Methods
Healthy subjects (54M) were enrolled into a randomized, placebo-controlled, double-masked, subsequent-group study. Topical ocular LAQ (10 mg/mL) was administered as single-ascending doses of 0.23-1.2 mg LAQ, or as multiple-ascending doses of 0.3-0.6 mg LAQ once daily for up to 21 days. Adverse events (AEs), standard eye exams and ocular symptoms were assessed. Albino rabbits (5M) received 0.9 mg LAQ/eye daily over 6 days. On day 7, 0.3 mg was administered and, at five time-points post-dose animals were sacrificed, one each time. The eyes were enucleated and LAQ quantified in eye sections using MALDI imaging.
Results
AEs were mostly mild or moderate. Only one severe AE (unrelated to LAQ) was reported. No serious AEs were reported. None of the ocular assessments revealed any eye toxicity. LAQ was detected in cornea at +0.5 and +1 hr post-dose, and in retina/choroid from +4 hrs post-dose.
Conclusion
Topical ocular LAQ demonstrated to be safe and tolerable in healthy subjects. Intra-ocular LAQ distribution was demonstrated in rabbit. Collectively, these results warrant clinical studies in patients with inflammatory eye disorders.
Conflict of interest
Yes
Details of conflicting interests
Garhöfer G, Schmidl D: none; Bondesson E, Ekberg P, Tuvesson H, Törngren M, Vahtola E: Active Biotech employment and share-holding
Authors 1
Last name
GARHöFER
Initials of first name(s)
G
Department
Department of Clinical Pharmacology
City
Vienna
Country
Austria
Authors 2
Last name
Bondesson
Initials of first name(s)
E
Department
Active Biotech
City
Lund
Country
Sweden
Authors 3
Last name
Ekberg
Initials of first name(s)
P
Department
Active Biotech
City
Lund
Country
Sweden
Authors 4
Last name
Schmidl
Initials of first name(s)
D
Department
Department of Clinical Pharmacology
City
Vienna
Country
Austria
Authors 5
Last name
Tuvesson
Initials of first name(s)
H
Department
Active Biotech
City
Lund
Country
Sweden
Authors 6
Last name
Törngren
Initials of first name(s)
M
Department
Active Biotech
City
Lund
Country
Sweden
Authors 7
Last name
Vahtola
Initials of first name(s)
E
Department
Active Biotech
City
Lund
Country
Sweden
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