The principal eye drug for Age-Related Macular Degeneration [AMD] is Lucentis from Roche (RHHBY).
Alternatives are Avastin, also from Roche and Eylea from Regeneron Pharmaceuticals (REGN). A newly promising drug, not approved yet, is Fovista from Ophthotech, a private US biotech, based in Princeton, New Jersey. All these drugs have to be injected directly into the eye by a doctor.
Age-related macular degeneration is a nasty disease of the eye. It characteristically affects people over 50 and is the leading cause of blindness in developed countries around the world.
AMD is very common, currently affecting about 8 million Americans and an additional 8 million Europeans. It is estimated that approximately 6% of individuals 65-74 years of age, and 20% of those older than 75 years of age are affected with AMD in the U.S. Because of the increasing life expectancy worldwide, in the absence of treatment measures, the number of cases of AMD with visual loss will grow dramatically.
The "dry" form of AMD is characterized by a slow degeneration of the macula resulting in atrophy of the central retina, with gradual loss of vision over a period of years. There is currently no approved therapy for dry AMD.
By contrast, "wet" AMD typically causes sudden, often substantial, loss of central vision. Wet AMD accounts for 10 percent of all AMD, and is responsible for 80 percent of the associated vision loss. Each year in the US alone, 155,000 new patients are diagnosed with wet AMD.
The vision loss in wet AMD is caused by the growth of abnormal leaky blood vessels that eventually damage the area of the eye responsible for central vision. AMD drugs are designed to block new blood vessel growth and leakiness. In 2011, Lucentis brought in sales at 1,523 billion Swiss francs (approx. $1.689 billion) . It is a genuine blockbuster, although lately its sales growth seems to be leveling off. In the first quarter of 2012, Lucentis sold $427 million worth of drugs.
In the same period Regeneron's Eylea sold $124 million. FDA approved Eylea in November, 2011, so this is a pretty strong launch. Many doctors prescribe a third drug, off-label Avastin, made also by Roche. It seems to work just as well, and it is substantially cheaper than either of the other two. Avastin costs approximately $50 per injection, while Lucentis is priced about $2,000 per injection. The reason for the difference is that Avastin is a cancer drug, and for the injection into the eye, they use only a fraction of the dose given cancer patients.
All three of these drugs, Lucentis, Eylea and Avastin work by blocking a protein called VEGF that stimulates the growth of new blood vessels, a hallmark of the wet macular degeneration. When VEGF is overexpressed, it can contribute to disease. In May 2012, two studies, carried out for the US National Eye Institute in the US and the National Health Service in the UK, found that Avastin and Lucentis, are equally effective treating wet age-related macular degeneration.
Roche has however stated that it does not promote Avastin's use as a treatment for wet AMD, and that it is not going to seek a license for that illness. Since Avastin is packaged in vials that exceed the 1.25-milligram dose commonly used for treating wet AMD, physicians often use compounding pharmacies to repackage it into single-use syringes that contain the smaller intravitreal dose. Consequently, there is some infection risk using Avastin.
Eylea's main benefit over Lucentis is that it can be dosed every other month, while Lucentis has to be dosed monthly. Less frequent dosing is always a benefit, especially when it comes to injections into the eye.
Fovista from Ophthotech:
In a recent phase 2b trial, 449 patients with wet AMD received the combination of Fovista and Lucentis. The patients have gained a mean vision improvement of 10.6 letters on the standard eye chart in 24 weeks, compared to 6.5 letters for those receiving Lucentis. This represents a 62% additional benefit.
It is considered extraordinary to achieve a 62% relative visual benefit over anti-VEGF monotherapy. This was the first-ever clinical trial to show better results than Regeneron's Eylea. The venture capitalists backing Ophthotech include SV Life Sciences, Clarus Ventures, HBM Partners and Novo A/S owned by the Novo Nordisk Foundation. Fovista uses anti-PDGF therapy.
Growth factor PDGF-B regulates cells associated with the walls of newly formed small blood vessels. Fovista binds to PDGF-B with high specificity and inhibits the functions of PDGF-B both in the lab and in the clinic. Fovista is an aptamer. Aptamers are DNA or RNA molecules that represent a new technology. While aptamers are analogous to antibodies in their ability of target recognition and variety of applications, they possess several key advantages. They are easier and more economical to produce on large scale. In contrast to peptides, proteins and to some small chemicals, DNA aptamers are made by chemical synthesis, a process that is well-defined, highly reproducible and can be readily scaled up. Their production does not depend on bacteria, cell cultures or animals.
Fovista may make a great add-on to existing AMD eye drugs. In the meantime, the search goes on for new drugs, combinations of existing ones and new devices to cure AMD. The US government clinical trial database lists 184 phase 3 studies under "macular degeneration".
Ohr Pharmacutical (OHRP.OB), a New York based company, has a great idea: Squalamine Eye Drops. They came up with an eye drop that is as effective as the currently applied injections, that can be self administered by the patient, with a convenience and great savings that this arrangement brings. If it works, this idea is a winner.
Using the intravenous formulation in over 250 patients in Phase 1 and Phase 2 trials for the treatment of wet-AMD, Squalamine demonstrated favorable biologic effect and maintained and improved visual acuity (sharpness of vision) outcomes, with both early and advanced lesions responding.
Squalamine is an anti-angiogenic small molecule with a novel mechanism of action, that targets not only VEGF but also other angiogenic growth factors such as PDGF with high potency concentrations. Recent clinical evidence (see Fovista) has shown that PDGF is a valid additional target for the treatment of wet-AMD. The company is planning to start phase 2 trials later in 2012. Also, Ohr has been awarded a fast tract designation by the FDA.
Disclosure: I have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.