Learn more about Fovista, and the future of treatments for this form of macular degeneration.

Patients with wet age-related macular degeneration (AMD) are helped by drugs that are injected into the back of the eye to block the growth and leakage of abnormal blood vessels. Current treatments include bevacizumab (Avastin™), ranibizumab (Lucentis™), and  aflibercept (Eylea™). 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.

Combining Treatments

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.  Avastin, Lucentis and Eylea are called “anti-VEGF agents” because they target vascular endothelial growth factorr (VEGF), a protein that binds to cells on the inner lining of blood vessels (vascular endothelial cells) and promotes their growth and leakage. Another potential target is platelet derived growth factor (PDGF), which binds to cells on the outer lining of blood vessels (pericytes).

Fovista™ blocks PDGF, and is now undergoing testing in clinical trials in combination with anti-VEGF drugs. In theory, combining it with an anti-VEGF drug could be even more effective than the anti-VEGF drug alone. When tested in a Phase 2 clinical trial with over 600 patients, where Fovista was combined with the anti-VEGF agent Lucentis, 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.

However, the Fovista phase III trial, which enrolled more than 1000 patients and is more definitive than the Fovista phase II trial, showed no benefit for visual acuity after 12 months of treatment compared to Lucentis alone. While these results are disappointing, it remains to be seen whether Fovista, in combination with Lucentis, might be able to reduce the number of required doctor visits and injections, or result in more stable vision in the long term. It also remains possible that ongoing clinical trials combining Fovista with Eylea or Avastin will show more benefit than Fovista plus Lucentis. The chance of benefit in combination with Eylea is diminished by results of a phase II trial showing no additional benefit when an anti-PDGF drug was added to Eylea.

There is still some hope for anti-PDGF drugs. 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. These effects might not become apparent in a one year clinical trial.

Clinical Trials

In the clinical trials, Fovista was 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. While the Fovista phase III trial demonstrated an increase in complications related to the additional injections, the Fovista drug itself showed no evidence of side effects.

The Future

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. 

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. Whether Fovista can decrease the number of required injections or improve vision in the long term is yet to be seen.

Whether or not anti-PDGF drugs prove useful, it is likely that drugs that target other disease-promoting proteins in both wet and dry AMD will benefit patients in a 5-10 year timeframe.