Aflibercept, ipilimumab, and vemurafenib

Agent for macular degeneration Acute central vision is necessary for recognizing faces and for activities such as reading and driving. Age-related macular degeneration (AMD) is a chronic, progressive disease of the macula that can result in the loss of central vision, and it is a common cause of blindness in older adults. More than 200,000 Americans are diagnosed each year with AMD. There are two general types of AMD: neovascular (wet) and nonneovascular (dry). In neovascular AMD, abnormal blood vessels leak blood and fluid into the retina, resulting in damage to the macula and impairment of central vision but not peripheral vision. It accounts for only 10% of the cases of AMD but is more severe and rapidly progressive than the dry type. Vascular endothelial growth factor (VEGF)-A and placental growth factor (PlGF) are members of the VEGF family of angiogenic factors, the overexpression of which can result in vascular leakage and progressive vision loss. VEGF acts via two receptor tyrosine kinases, VEGFR-1 and VEGFR-2, that are present on the surface of endothelial cells, whereas PlGF binds only to VEGFR-1. Activation of these receptors by VEGF-A can result in neovascularization and vascular permeability. Aflibercept (Eylea—Regeneron) is the fourth drug to be approved for the treatment of neovascular AMD, joining verteporfin (Visudyne), which is used in a two-stage photodynamic treatment; pegaptanib (Macugen); and ranibizumab (Lucentis). The latter two agents are VEGF antagonists that are administered via intravitreal injection, as is bevacizumab (Avastin), an agent that has been used in the treatment of several types of cancer but has also been used off-label for the treatment of AMD. Aflibercept is a recombinant fusion protein consisting of portions of human VEGFR-1 and VEGFR-2 extracellular domains fused to the Fc portion of human IgG1. It acts as a decoy receptor that binds VEGF-A and PlGF, thereby inhibiting the binding and activation of VEGF receptors. It is administered by ophthalmic intravitreal injection and is indicated for the treatment of patients with neovascular (wet) AMD. The effectiveness of aflibercept was demonstrated in two studies in which it was compared with ranibizumab. The primary efficacy endpoint was the proportion of patients who maintained vision at week 52 compared with baseline. Approximately 95% of patients maintained visual acuity, and the patients in the groups treated with aflibercept 2 mg every 4 weeks and 2 mg every 8 weeks experienced efficacy that was clinically equivalent to the patients treated with ranibizumab 0.5 mg every 4 weeks. Additional efficacy was not demonstrated when aflibercept was administered every 4 weeks compared with every 8 weeks. Ranibizumab is also indicated for the treatment of macular edema following retinal vein occlusion. However, this is not a labeled indication for aflibercept at the present time. The use of aflibercept is contraindicated in patients with ocular or periocular infection or with active intraocular inflammation. Intravitreal injections have been associated with the occurrence of endophthalmitis (severe inflammation of the interior of the eye) and retinal detachments, and patients should be advised to promptly contact their physician if the eye becomes red, sensitive to light, or painful or if a change in vision develops. Acute increases in intraocular pressure (IOP) have been experienced within 60 minutes of intravitreal injection, and some patients may experience sustained increases in IOP. Arterial thromboembolic events (e.g., nonfatal stroke, vascular death) are possible following the intravitreal injection of VEGF inhibitors, and the incidence of such events in the clinical studies during the first year was 1.8%. The adverse events most commonly experienced in the clinical studies of aflibercept included conjunctival hemorrhage (25%), eye pain (9%), cataract (7%), vitreous detachment (6%), vitreous floaters (6%), and increased IOP (5%). The incidence of these events was similar to that experienced by the patients treated with ranibizumab, and many of these responses were probably attributable to the injection procedure rather than to the medication. Aflibercept is classified in Pregnancy Category C and should only be used during pregnancy if the anticipated benefit justifies the risk to the fetus. The recommended dosage of aflibercept is 2 mg (0.05 mL) by intravitreal injection every 4 weeks (monthly) for the first 12 weeks (3 months), followed by 2 mg once every 8 weeks (2 months). Administering the new drug every 8 weeks provides an important advantage over ranibizumab, which is usually administered once a month, although some patients are treated less often. Aflibercept injection is supplied in single-use vials designed to deliver 0.05 mL of a solution containing the drug in a concentration of 40 mg/mL. The vials should be stored in a refrigerator. Adequate anesthesia and a topical broadspectrum microbicide should be given before the injection. The needles and syringes supplied with the medication should be used in withdrawing the solution from the vial and for administration via intravitreal injection. Each vial should only be used for the treatment of a single eye