Europe gives Macugen thumbs up

March 1, 2006

The month of February witnessed the first approval of an anti-angiogenesis therapy for the treatment of age-related macular degeneration (AMD) in Europe. The European Commission granted marketing authorisation for Macugen (pegaptanib sodium injection) for the treatment of neovascular AMD.

Macugen targets the protein, and potent angiogenic factor, VEGF 165, a known mediator of choroidal neovascularization and thus all subtypes of AMD.

The approval was based on the achievement of the primary efficacy endpoint, defined as the proportion of patients protected from a three-line loss of visual acuity by week 54, in two clinical trials involving 1186 patients with all subtypes of neovascular AMD. Trials demonstrated a loss of less than three lines of vision in 70% of patients who had received 0.3 mg Macugen every six weeks compared with 55% of patients who received sham therapy after one year, thus cementing the agent's reputation as a successful foundation monotherapy. The agent demonstrated continued benefit in those patients who continued treatment for a second year.

Macugen is also showing promise as combination therapy. In a separate presentation, given by Lawrence J. Singerman, MD, president of Retina Associates of Cleveland, clinical professor of ophthalmology, Case Western Reserve University School of Medicine Cleveland and voluntary professor of clinical ophthalmology at the Bascom Palmer Eye Institute, Miami, USA, at the AAO annual meeting in Chicago last year. In a small group of patients who received photodynamic therapy (PDT) and pegaptanib sodium in a Phase Ib study, 60% gained three or more lines of vision, compared with 25% of patients who received pegaptanib sodium alone.

"Combination therapy may be the way to go," said Singerman. Various trials of combination therapies are ongoing. One such study, being conducted by Eyetech (OSI Pharmaceuticals), is of pegaptanib sodium plus sham PDT compared with pegaptanib sodium plus PDT. A second study is comparing PDT plus two different doses of intravitreal triamcinolone acetonide with PDT plus pegaptanib sodium.

"It is logical that attacking the disease process at multiple steps in its pathway should improve the results if the right drugs are being used," he said. "These drugs may be those that work best together and not necessarily the most effective monotherapies. Combination therapies will be studied extensively and we hope ranibizumab (Lucentis, Novartis), anecortave acetate (Retaane, Alcon) and other drugs will be approved soon so that we can study the enhanced benefit that they might offer to our patients in various combinations," Singerman said.

"Anti-VEGF therapy has been validated as the foundation therapy for AMD. Evidence-based medicine should drive practice patterns. Combination therapy should improve results. Early treatment of earlier disease is better and anti-VEGF therapy will have a wider role to play than just in AMD," he concluded.

Macugen is marketed for the treatment of all types of neovascular AMD in the US, Canada, Brazil, Argentina, Peru, Pakistan and the Philippines, with marketing authorizations pending in 15 other countries. Pfizer and OSI Pharmaceuticals jointly market Macugen in the US whilst Pfizer has exclusive development and marketing rights outside of the US.

FDA approves Xibrom expanded indication

The FDA has approved ISTA Pharmaceuticals' supplemental New Drug Application (sNDA) for Xibrom (0.09% bromfenac ophthalmic solution), expanding its indications to include the treatment of pain following cataract surgery.

Originally approved by the FDA in March 2005 for the treatment of ocular inflammation following cataract surgery, Xibrom is a topical, twice-daily, non-steroidal anti-inflammatory drug (NSAID) solution.