March 2010




Starting with the basics

by Matt Young EyeWorld Contributing Editor

Central blindness that can be caused by age-related macular degeneration Source: Acucela

As major drug companies continue to vie for turf in the wet age-related macular degeneration market, one small biotech company has taken a step back from the fray, focusing on a treatment for dry AMD, which currently has no cure, but in every instance predates the wet form. Bothell, Wash.-based Acucela got its corporate start back in 2002 when Ryo Kubota, M.D., Ph.D., then an assistant professor at the University of Washington School of Medicine, Seattle, realized that visual cycle modulation deserved a place in society well outside of the ivory tower. As founder, chairman, president, and CEO of Acucela, Dr. Kubota has spearheaded the push of ACU-4429—a visual cycle modulator for dry AMD—far through the pipeline of pharmaceutical development. The drug, which comes in pill form, aims to slow down the activity of the eye’s rods. Most people remember from science class that light receptor cells known as rods are responsible for night vision, while cones are responsible for daytime vision. However, as rods are much more numerous and active, it has been shown that their over-activity can be toxic. “We get most of our visual information from the cone system,” Dr. Kubota said. “But we have 90% rods, which are not being utilized properly, and generate a lot of toxic byproducts.” Rod cell deterioration is common as eyes age, according to Acucela, and this is a cause of AMD. If ACU-4429 indeed comes to market, along with Acucela’s other experimental drugs, the company could be a major ophthalmic pharmaceutical contender.

Vast market for a new treatment

ACU-4429 is currently in Phase II clinical trials for the Food and Drug Administration. The drug is targeting a massive patient audience, which currently has no other treatment choice. AMD afflicts about 30 million people worldwide and is the leading cause of blindness in people more than 50 years old. The “wet” form, which is treatable and is a current cash cow for major multinationals, affects only 10% of all AMD patients. That leaves the other 90% of the world’s AMD patients with the dry form, which Acucela calculates to be 26 million people and a $4 billion market. So far, the best science has been able to offer these patients has been nutritional supplements “which may or may not work,” Dr. Kubota said. They’re certainly not put through rigorous clinical trials testing safety and efficacy. The other choice is to wait to get full-blown wet AMD, for which there is treatment, but why wait for end-stage disease to get treated if you don’t have to? The symptoms of dry AMD include blurred vision, which eventually progresses to create a “blind spot” and gradual loss of central vision. By comparison, the wet form causes sudden, severe loss of central vision. “We want to go upstream and protect patient vision before it’s too late,” Dr. Kubota said. “The later stage it is, the less chance the patient has of regaining vision.”

The goal of ACU-4429 is to target the earlier stages of AMD and in pill form, which nonetheless focuses on molecules specific to the eye. A Phase I clinical trial for the FDA, enrolling 58 patients, demonstrated the pill is very mild and well tolerated, resulting in non-serious adverse events, Dr. Kubota said. Acucela’s mission in terms of AMD, therefore, is twofold. “We would like to stop wet AMD from happening with ACU-4429,” Dr. Kubota said. “We would also like to change the AMD treatment paradigm from invasive therapy to non-invasive therapy.”

Other company advantages

Dr. Kubota believes ACU-4429 could have other applications as well. “Another important aspect of ACU-4429 is not only to reduce this toxic byproduct [of rods] but also to reduce major oxygen demand in the eye. We think we can use it for diabetic retinopathy where one has less blood supply to match the needs of oxygen consumption,” he said. Acucela is also championing rebamipide, an ophthalmic suspension for dry eye developed by Otsuka Pharmaceutical (Tokyo), a company partner. Rebamipide, in late stage clinical trials, stimulates production of mucin, which the company says is an important component of tear film. OcuScreen, another Acucela product, is a screening platform used to clarify molecular targets and identify lead compounds. Dr. Kubota is building his company “to last,” not to be bought out, he said. “Our intention for Acucela is to be a fully independent ophthalmology company that has a sales force as well,” Dr. Kubota said. “We’re a built-to-last model, not a built-to-sell model. The reason we can do that is because of the long-term support of Japanese investors who prefer us to be an existing company, as well as our partner Otsuka funding us, so we don’t have to rely on capital markets for the fundraising to develop our drug. We are very financially stable.”

Acucela has 34 employees. The company has raised more than $40 million from investors and has a strategic partnership with Otsuka to co-develop ACU-4429 and rebamipide.

Editors’ note: Dr. Kubota is founder, chairman, president, and CEO of Acucela (Bothell, Wash.).

Contact information

Kubota: 425-527-3260,

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