Regeneron Pharmaceuticals Inc. stormed onto the wet age-related macular degeneration (AMD) market with second quarter sales of Eylea (aflibercept injection) increasing 57 percent compared to their first quarter. The drug competes with Roche AG's Lucentis (ranibizumab) and off-label use from Avastin (bevacizumab). (See BioWorld Today, July 26, 2012.)

Ophthotech Corp. is also looking to move into the market with its wet AMD drug, Fovista, although the anti-platelet-derived growth factor will likely be tested in combination with Eylea or Lucentis rather than compete directly. (See BioWorld Today, June 14, 2012.)

Rather than entering the competitive wet AMD foray, some biotechs are focusing on the dry form of the disease. This early form of AMD converts into the wet form when abnormal blood vessels behind the retina start to grow under the macula.

Preventing or delaying the progression from dry to wet AMD is beneficial because the wet form of the disease leads to vision loss, but to date there are no treatments for dry AMD.

Phil Ralston Jr., CEO of MacuClear Inc., hopes to change that with his company's drug candidate MC-1101 that can be delivered via an eye drop.

"Wet AMD is like having a heart attack and then treating it with a stent or bypass surgery. Let's treat the disease – like with Lipitor – and prevent it from ever getting to the wet stage," Ralston told BioWorld Insight.

Other companies have tried to treat dry AMD with antioxidants – Othera Pharmaceuticals Inc.'s OT-551 for example – but Ralston said the oxidative stress is just a symptom of larger problem: a lack of ocular blood flow in the choroidal vessels.

"We know that blood brings nutrients to tissue and takes waste away. When that is compromised, you get waste product buildup and in our coronaries and peripheral arteries that's plaque that precludes vessels. We think the same thing happens in the eye," Ralston explained.

MacuClear identified 13 compounds to restore blood flow, but chose to start with MC-1101 because it has been previously approved as an oral anti-hypertensive compound and therefore can gain approval under the FDA's 505(b)(2) pathway.

In a Phase Ib trial, MC-1101 reached the back of the eye and modulated the blood flow in the choroid, tiny blood vessels in the back of the macula portion of the eye.

The firm plans to begin a Phase III trial to test its hypothesis. Unlike wet AMD drugs, whose efficacy can be measured by vision improvement on an eye chart, the changes in dry AMD are more subtle and would take years to measure meaningful changes using visual acuity. Instead MacuClear plans to use improvements in visual function, the ability to see in the dark for example, to measure MC-1101's ability to delay progression of dry AMD.

Given the unmet need, MacuClear isn't the only company trying to move into the untapped market. Ophthotech Corp., ReVision Therapeutics Inc., RetroSense Therapeutics LLC and PanOptica Inc. all have dry AMD treatments in various stages of development. (See BioWorld Today, Dec. 15, 2009, Sept. 1, 2010, Jan. 4, 2011, and Jan 23, 2012.)

With 90 percent of AMD patients who have the dry form there's plenty of market share to go around. Ralston estimates small-molecule drugs to treat dry AMD can be sold for a fraction of the cost of biologics that treat wet AMD and still create a $5 billion market.