Phase 3, Randomized, 20-Month Study of the Efficacy and Safety of Bimatoprost Implant in Patients with Open-Angle Glaucoma and Ocular Hypertension (ARTEMIS 2)

Objective- To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of 10 and 15 µg bimatoprost implant in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). Methods- This randomized, 20-month, multicenter, masked, parallel-group, phase 3 trial enrolled 528 patients with OAG or OHT and an open iridocorneal angle inferiorly in the study eye. Study eyes were administered 10 or 15 µg bimatoprost implant on day 1, week 16, and week 32, or twice-daily topical timolol maleate 0.5%. Primary endpoints were IOP and IOP change from baseline through week 12. Safety measures included treatment-emergent adverse events (TEAEs) and corneal endothelial cell density (CECD). Results- Both 10 and 15 µg bimatoprost implant met the primary endpoint of noninferiority to timolol in IOP lowering through 12 weeks. Mean IOP reductions from baseline ranged from 6.2–7.4, 6.5–7.8, and 6.1–6.7 mmHg through week 12 in the 10 µg implant, 15 µg implant, and timolol groups, respectively. IOP lowering was similar after the second and third implant administrations. Probabilities of requiring no IOP-lowering treatment for 1 year after the third administration were 77.5% (10 µg implant) and 79.0% (15 µg implant). The most common TEAE was conjunctival hyperemia, typically temporally associated with the administration procedure. Corneal TEAEs of interest (primarily corneal endothelial cell loss, corneal edema, and corneal touch) were more frequent with the 15 than the 10 µg implant and generally were reported after repeated administrations. Loss in mean CECD from baseline to month 20 was ~ 5% in 10 µg implant-treated eyes and ~ 1% in topical timolol-treated eyes. Visual field progression (change in the mean deviation from baseline) was reduced in the 10 µg implant group compared with the timolol group. Conclusions- The results corroborated the previous phase 3 study of the bimatoprost implant. The bimatoprost implant met the primary endpoint and effectively lowered IOP. The majority of patients required no additional treatment for 12 months after the third administration. The benefit-risk assessment favored the 10 over the 15 µg implant. Studies evaluating other administration regimens with reduced risk of corneal events are ongoing. The bimatoprost implant has the potential to improve adherence and reduce treatment burden in glaucoma

Cooperación empresarial en la que intervienen firmas brasileñas y argentinas: primeras reflexiones que surgen del trabajo de campo

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Repeated, but not single, VEGF gene transfer affords protection against ischemic muscle lesions in rabbits with hindlimb ischemia

Vascular endothelial growth factor (VEGF) gene transfer-mediated angiogenesis has been proposed for peripheral artery disease. However, protocols using single administration have shown little benefit. Given that the transient nature of VEGF gene expression provokes instability of neovasculature, we hypothesized that repeated administration would provide efficient tissue protection. We thus compared single vs repeated transfection in a rabbit model of hindlimb ischemia by injecting a plasmid encoding human VEGF165 (pVEGF165) at 7 (GI, n=10) or 7 and 21 (GII, n=10) days after surgery. Placebo animals (GIII, n=10) received empty plasmid. Fifty days after surgery, single and repeated administration similarly increased saphenous peak flow velocity and quantity of angiographically visible collaterals. However, microvasculature increased only with repeated transfection: capillary density was 49.4±15.4 capillaries per 100 myocytes in GI, 84.6±14.7 in GII (P<0.01 vs GI and GIII) and 49.3±13.6 in GIII, and arteriolar density was 1.9±0.6 arterioles per mm2 in GI, 3.0±0.9 in GII (P<0.01 vs GI and GIII) and 1.5±0.6 in GIII. Muscle lesions were reduced only within repeated transfection. With single administration, gene expression peaked at 7 days and declined rapidly, but with repeated administration, it remained positive at 50 days. At 90 days of repeated transfection (additional animals), gene expression decreased significantly, but neovessel densities did not. Thus, repeated, but not single, VEGF gene transfection resulted in increased microvasculature, which, in turn, afforded effective protection against ischemic muscle damage.Fil: Olea, Fernanda Daniela. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Vera Janavel, G.. Universidad Favaloro. Área de Investigación y Desarrollo; ArgentinaFil: Cuniberti, Luis Alberto. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Yannarelli, Gustavo Gabriel. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cabeza Meckert, Patricia. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; ArgentinaFil: Cors, J.. Universidad Favaloro. Área de Investigación y Desarrollo; ArgentinaFil: Valdivieso, L.. Universidad Favaloro. Área de Investigación y Desarrollo; ArgentinaFil: Lev, G.. Universidad Favaloro. Área de Investigación y Desarrollo; ArgentinaFil: Mendiz, O.. Universidad Favaloro. Área de Investigación y Desarrollo; ArgentinaFil: Bercovich, A.. Universidad Favaloro. Área de Investigación y Desarrollo; ArgentinaFil: Criscuolo, M.. Biosidus S. A.; ArgentinaFil: Melo, C.. Biosidus S. A.; ArgentinaFil: Laguens, R.. Universidad Favaloro. Área de Investigación y Desarrollo; ArgentinaFil: Crottogini, Alberto José. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin