International Approvals: Retaane, Avelox, Generic Zinnat

Yael Waknine

December 19, 2005

Dec. 19, 2005 —Australia's Therapeutic Goods Administration has approved anecortave acetate 15-mg suspension for depot injection in the treatment of subfoveal choroidal neovascularization due to exudative (wet) age-related macular degeneration where there is a classic component; Japan's Ministry of Health, Labor, and Welfare has approved moxifloxacin HCl 400-mg tablets for the treatment of indicated infections caused by susceptible microorganisms; and Denmark's Medicines Authority has approved first-time generic formulations of cefuroxime axetil 250- and 500-mg tablets for the treatment of indicated infections caused by susceptible microorganisms.


Anecortave Acetate Suspension (Retaane) for CNV Due to Wet AMD in Australia

On December 12, Australia's Therapeutic Goods Administration approved anecortave acetate 15-mg suspension (Retaane, made by Alcon, Inc) for the treatment of subfoveal choroidal neovascularization (CNV) due to exudative (wet) age-related macular degeneration (AMD) where there is a classic component.

Anecortave acetate is a novel steroid analog (cortisene) of cortisol acetate that has been modified by removal of the 11ß hydroxyl group and the addition of a 21-acetate group. As a result, it lacks the anti-inflammatory and immunosuppressive properties that can cause adverse events such as cataract development and elevated intraocular pressure leading to glaucoma.

The drug functions instead as an angiostatic agent, inhibiting blood vessel growth by decreasing extracellular protease expression and inhibiting endothelial cell migration. It is administered every 6 months as a depot delivered behind the eyeball using a blunt-tipped, curved cannula to decrease the risks of intraocular infection and retinal detachment.

The approval was based in part on data from a phase 2 study showing that 73% of patients treated with anecortave acetate had stable or improved vision at 24 months compared with 47% of patients who did not receive the drug (P = .035).

Treated patients exhibited no growth of the classic component of the subfoveal CNV between 1 and 2 years, and lesion size remained stable. Among a subset of patients with aggressive, predominantly classic CNV lesions, severe vision loss occurred in no patients at 2 years posttherapy compared with 23% of those in the placebo group (P = .023).

In addition, results of a phase 3 clinical study comparing anecortave acetate and photodynamic therapy using verteporfin (Visudyne, made by Novartis AG), showed that both treatment methods were similarly effective in maintaining vision at 1 year (45% vs 49%).

According to company information, drug reflux and extended treatment intervals may have decreased treatment efficacy. Vision maintenance rates were higher among patients who did not experience reflux at the second dose (50% vs 39%; P = .105), and among those who received the second depot within 182 days of the initial treatment (50% vs 33%; P = .021). A counterpressure device has since been developed to control drug reflux during administration.

According to a company news release, a multicenter, randomized, prospective US clinical trial of anecortave acetate suspension is being planned in conjunction with the National Eye Institute. The study will enroll patients with all forms of wet AMD who are being treated with intravitreal bevacizumab (Avastin, made by Genentech, Inc). The product was deemed "approvable" by the US Food and Drug Administration in May 2005.


Moxifloxacin 400-mg Tablets (Avelox) for Multiple Indications in Japan

On December 9, moxifloxacin HCl 400-mg tablets (Avelox, marketed by Shionogi and Company, Ltd, under license from Bayer Yakuhin, Ltd) were launched on the Japanese market.

The product was approved by Japan's Ministry of Health, Labor, and Welfare in October 2005 for the treatment of superficial and deep skin infections; burns and surgical wounds; pharyngitis; laryngitis; tonsillitis; acute bronchitis; pneumonia; secondary infections of chronic respiratory diseases; and sinusitis caused by susceptible strains of microorganisms.

The approval was based on an analysis of data from 3 Japanese and 15 non-Japanese clinical trials that confirmed the efficacy of moxifloxacin therapy in patients with respiratory tract infections, dermatologic infections, and acute sinusitis. Indications evaluated only in the Japanese trials included pharyngo-laryngitis, tonsillitis, and acute bronchitis.

Moxifloxacin tablets are approved by the US Food and Drug Administration for the treatment of adults with uncomplicated and complicated skin and skin structure infections; community-acquired pneumonia; acute bacterial exacerbation of chronic bronchitis; and acute bacterial sinusitis caused by susceptible strains of microorganisms.


First-Time Generic Cefuroxime Axetil 250- and 500-mg Tablets (Zinnat) in Denmark

On November 7, the Danish Medicines Authority approved first-time generic formulations of cefuroxime axetil 250- and 500-mg tablets (made by Orbus Pharma, Inc; brand name Zinnat/Ceftin, made by GlaxoSmithKline).

The approval will allow Denmark to initiate the mutual recognition procedure in pursuit of regulatory approvals from other European Union countries.

Cefuroxime tablets are approved by the European Commission and US Food and Drug Administration for the treatment of infections caused by susceptible microorganisms. Respiratory indications include pharyngitis/tonsillitis, acute bacterial otitis media, acute maxillary sinusitis, acute exacerbations of chronic bronchitis, and secondary bacterial infections of acute bronchitis.

Additional indications include uncomplicated skin/skin structure and urinary tract infections; uncomplicated gonorrhea; and early erythema migrans (Lyme disease).

Reviewed by Gary D. Vogin, MD

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