Article title: Small molecules as therapy for uveitis: a selected perspective of new and developing agents
Authors: Pleyer, U., Algharably, E., A-H., Feist, E., & Kreutz, R.
Journal: EXPERT OPINION ON PHARMACOTHERAPY
Bibliometrics: Volume 18, Number 13, pages 1311–1323
DOI: https://doi.org/10.1080/14656566.2017.1361408
Since the publication of the article, a query was raised to the editor highlighting section 3.9.1 in the article where the reference included [Diedrichs-Mohring M, Leban J, Strobl S, et al. A new small molecule for treating inflammation and chorioretinal neovascularization in relapsing-remitting and chronic experimental autoimmune uveitis. Invest Ophthalmol Vis Sci. 2014;56:1147–1157] was considered insufficient to substantiate the information provided. After our investigation, this was confirmed and the section was subsequently removed from the article.
The removed text was:
“3.9.1. PP-001
PP-001 is a third-generation small-molecule inhibitor of DHODH with a half-maximal inhibitory concentration (IC50) below 4 nM (1.9 ng/ml). PP-001 has been proven as effective to ameliorate uveitis in an EAU rat model [88]. It is structurally different from earlier DHODH inhibitors such as leflunomide and does not inhibit tyrosine kinases and their respective pathways.
Proof of concept for PP-001 in the treatment of noninfectious uveitis was established in a rat EAU model following oral and intravitreal administration of PP-001 [88]. In these studies, PP-001 was shown to be effective in prevention and treatment of experimentally induced autoimmune uveitis. Treatment with PP-001 at an oral dose level of 25 mg/kg significantly reduced the number of relapses and their intensity when compared to control. The corresponding ocular exposures as estimated by pharmacokinetic analysis as area under the curve were 1.27 and 4.8 µg·h/g for vitreous and retina, respectively. Intravitreally dosed PP-001 (3 µg/eye) reduced the number of relapses per eye by 50% when compared to control. The 14-day i.v. repeated dose toxicity study in rats did not show evidence for adverse effects on safety pharmacology parameter even at the highest dose tested (1 mg/kg body weight).
Currently, a phase I study on the use of intravitreal PP-001 is conducted. The systemic exposure in humans is expected to be below the minimal biologically active concentration for T cells (IC50 958 ng/ml). Thus, no stand-alone in vivo safety pharmacology studies were conducted.”