Fovista® Treatment for wet Age-Related Macular Degeneration (AMD).

Fovista is a promising new treatment for wet AMD is currently in Phase 3 clinical trials. It is designed to target platelet derived growth factor (PDGF) in combination with anti-VEGF drugs to disrupt the formation of abnormal new blood vessels in wet AMD.

Patients with wet AMD are helped by drugs that block the growth and leakage of abnormal blood vessels. Currently, the most frequently used drugs that are injected into the eye are Eylea®, Lucentis®, or Avastin®. On average, patients who receive one of these drugs gain vision for the first two years after initiating treatment, but some patients do not gain vision, and some who initially improved will still lose vision over time. This has motivated the development of additional drugs to block abnormal blood vessels. As with cancer chemotherapy, a combination of drugs with different molecular targets is often more effective than a single drug.  Lucentis, Eylea, and Avastin all target vascular endothelial growth factor (VEGF), a protein that binds to cells on the inner lining of blood vessels (vascular endothelial cells) and promotes their growth and leakage. Another promising target is platelet derived growth factor (PDGF), which binds to cells on the outer lining of blood vessels (pericytes).

Fovista blocks PDGF. So, in theory, combining it with an anti-VEGF drug could be even more effective than the anti-VEGF drug alone. This was tested in a Phase 2 clinical trial with over 600 patients. The result was a significantly higher average visual acuity gain at the 24-week time point in patients who received a combination of Fovista plus Lucentis than Lucentis alone. This is very encouraging. Anti-VEGF drugs are typically very effective at stopping leakage from abnormal blood vessels, but these vessels often survive the treatment and begin leaking again later, or even evolve into damaging scar tissue. Anti-PDGF drugs have the potential to promote blood vessel regression and reduce scarring. However, more testing is needed before we know whether Fovista is safe and effective over a longer period. Only then could it be approved by the FDA and available to patients outside clinical trials.

Currently, Fovista is injected through a separate needle from the anti-VEGF drugs, requiring two separate injections. The injections can be performed during the same office visit, but not necessarily one right after the other, as eye pressure can increase if too much fluid is injected into the eye at one time. Although complications from intraocular injections are rare, performing two separate injections may double the risk.  Risks of anti-VEGF injections include infection in the eye (endophthalmitis), retinal detachment, or cataract in patients who have not had cataract surgery to remove their natural lens. The risk of each of these complications is about 0.1 percent per injection. In an effort to reduce the risk of additional injections, it may be possible in the future to combine drugs so that only one injection is needed to deliver both of them in a small amount of fluid that would be unlikely to increase eye pressure to dangerous levels.

In clinical trials, the combination of Fovista® 1.5mg and an anti-VEGF therapy demonstrated statistically significant superiority compared to anti-VEGF monotherapy in terms of improvements in visual acuity, providing a 62% comparative benefit from baseline. Fovista® binds to and inhibits PDGF expression, causing the loss or stripping of pericytes, leaving the endothelial cells unprotected and highly vulnerable to the effects of anti-VEGF therapy. Clinical data have shown that administration of Fovista® 1.5mg in combination with anti-VEGF drugs is likely to inhibit new blood vessel growth in patients with wet AMD more effectively than anti-VEGF monotherapy and may also enhance neovascular regression.

Because of the success of anti-VEGF drugs, many patients with wet AMD are reading this article. Prior to these drugs, they would have lost their reading vision. Within a few years, drugs with recently discovered targets are likely to further improve vision in a larger percentage of treated patients, while decreasing injection frequency.

 

For more information please visit: www.brightfocus.org

eye_exam_of_senior_man