INNOVATION IN RETINA

Dr. Vernon G. Wong: A Pioneer in Sustained-Release Therapy

After Ozurdex success, he seeks new challenges to tackle.

EDITED BY Emmett T. Cunningham, MD, PhD, MPH, AND Pravin U. Dugel, MD

Jerry Helzner, Senior Editor

The Ozurdex implant, developed by Dr. Wong, treats macula edema secondary to RVO for 4 to 6 months and biodegrades in the eye.

Soft-spoken and down-to-earth, Vernon G. Wong, MD, FACS, is willing to acknowledge the truly prodigious series of accomplishments that led to him almost single-handedly developing the successful sustained-release implant Ozurdex, now used regularly by retina specialists for the treatment of macular edema associated with RVO and noninfectious uveitis.

However, he tempers the pride in his achievements with quiet, self-deprecating humor that is both endearing and disarming.

For example, asked about how he felt after Allergan paid $245 million to buy Oculex, the company he helped found and that developed Ozurdex, Dr. Wong says simply: “My investors made most of the money. I felt like I was out of a job and had to find something else to do.”

In the same vein, Dr. Wong ascribes a great deal of his success to “an understanding wife” who put up with workdays that went long into the night, and mentors such as Irving Leopold of Wills Eye, who Dr. Wong calls “the father of ocular pharmacology.”

In a wide-ranging, 90-minute interview for this column, Dr. Wong described a career marked by tremendous dedication to his work, great curiosity, several brilliant insights and a dogged determination to see his ideas through to fruition. Even now, at age, 80, Dr. Wong believes the best in sustained-release drug-delivery is yet to come. His most recent venture, Icon Bioscience, is working to create a sustained-release platform through which drugs can be delivered in solid, liquid, semi-liquid or gel formulations for almost any length of time. In other words, a tailor-made drug delivery system for each individual patient.

HARD WORK AND INITIAL SUCCESSES

Raised in Philadelphia in humble circumstances by parents who always encouraged him to excel, young Vernon Wong went to the best high school in the city and then on to Penn State University, where he majored in chemistry and physics. While back in Philadelphia for medical school at Thomas Jefferson, he at the same time worked on a doctorate in biochemistry at Johns Hopkins. A project at Johns Hopkins led him to find that vitamin B-12 and folic acid had an affinity for almost every tissue in the body except the eye and the brain. “A study of prisoners of war had shown that lack of B-12 in the diet led to blindness,” Dr. Wong recalls. “It was this research on B-12 that led me to become an ophthalmologist.”

After completing a broad-based ophthalmology residency at Penn, it was time for Dr. Wong, then in the Naval Reserve, to fulfill his military obligation in the Navy. However, the National Institutes of Health (NIH) was impressed with Dr. Wong's research and allowed him to work at the NIH as a clinical associate as an alternative to active duty.

“We had a wonderful situation at NIH,” he recalls. “We had 12 to 15 beds and could observe and treat patients with difficult eye diseases over long periods of time.”

Dr. Wong was especially interested in one group of patients who had chronic uveitis and could not be cured.

“I knew that some cancer drugs could treat inflammation, so I took it upon myself to treat these patients systemically with methotrexate and they all got better. The uveitis cleared up.”

A BIG LEAP BRINGS DETRACTORS

In the early 1960s, all eye diseases were treated topically and/or systemically (either with intra-muscular injections or intravenously). Dr. Wong had a flash of insight. He began to believe that local injections into the eye might be more effective.

Going against traditional thinking, he began to inject rabbit eyes with various dyes, and then drugs, to determine how long the dyes and drugs would stay in the eye.

“Some disappeared in three hours but other took 11 hours to clear,” he says. “I realized that each drug has a fundamental relationship to the eye. But no drug stayed in the eye for very long. This was the initial insight led me to first start thinking of a sustained-release format that could deliver a drug continuously over a period of time.”

After more than a decade at NIH, Dr. Wong was receiving offers from prestigious academic institutions around the country.

“My wife was comfortable in the Washington, DC area and our two sons were in school at the time, so the family pretty much decided that we should stay in the area,” he notes. “I received a nice offer from Georgetown and wound up staying the next 20 years.”

At Georgetown, in addition to his other work, Dr. Wong held the post of Director of Ocular Oncology at the Vincent T. Lombardi Cancer Center.

While at Georgetown, Dr. Wong got involved in his first business venture, a company called Visionex that was working to improve the basic Schirmer test for dry eye.

“I never got involved in the business side of it but we were able to improve the test by impregnating the paper strip with a dye and markings so that it would be easier to measure the results. It was a very simple innovation that's still in use today.”

A MOVE TO SILICON VALLEY

After many years at Georgetown and now a widower with his sons grown, Dr. Wong realized that he would not be able to pursue some of his more innovative ideas for sustained-release drug delivery at Georgetown. He moved to Silicon Valley in California, initially staying with an aunt in a small apartment.

By this time, he had decided that a polymer implant impregnated with a drug would be the best method for delivering eye drugs in a sustained-release format.

When no one in the research community would sell him basic polymers, he made a deal with a corn company in Clinton, Iowa, and made his own polymer, polylactic acid (PLA), out of corn fibers.

Verisome-based triamcinolone, developed by Icon BioScience, after injection into the vitreous of a patient.

“I had to use explosive ether to do it, so I turned on a big fan in the lab and hoped that it wouldn't explode,” he says. “When I came back in the morning, I had the most beautiful crystallized polymer.”

Dr. Wong had made some important contacts in California, including Bertram Rowland, a patent attorney who helped found Genenetch.

“We played a lot of tennis. One day he asked me how my work was going and I explained that I had made some progress with an implant for sustained-release drug delivery to the eye using a polymer. He told me to send him all the research about this concept, which I did.”

A few months later, Mr. Rowland called with the news that he had gotten a patent for Dr. Wong on the drug delivery system.

“He got me the patent and told me that I had to do something with it,” Dr. Wong chuckles. “I knew very little about business but I knew I had to start one.”

OCULEX: FROM STARTUP TO SUCCESS

Dr. Wong and Dr. Jerry Gin started Oculex in the early 1990s with funds from family and friends who liked the concept.

He had another friend in California who gave him access to a lab 24 hours a day. “I pretty much developed the drug that became Ozurdex on my own,” he says. “I had help from a wonderful woman chemist who said she would come in at 5 pm after her day job and work for free until we could get some more funding.”

Later, Dr. Wong hired several chemists from Roche who also believed in his concept. Additional funding came later from private individuals, venture capital and the government of Singapore.

“Oculex started out with two sustained-release drugs, Posurdex (a dexamethasone implant that is today called Ozurdex) and Surodex, a steroid implant following cataract surgery to reduce inflammation,” Dr. Wong recalls. “Surodex has been approved in China, Singapore and several other countries but Allergan never pursued approval in the United States after they bought Oculex.” Dr. Wong says Posurdex was a clinically proven drug by the time Allergan bought Oculex in 2002.

“We knew it worked,” he says. “I don't think Allergan would have paid that price if they hadn't known that it would be a success.”

ICON BIOSCIENCE: MOVING FORWARD

After the sale of Oculex, Dr. Wong was still looking for new worlds to conquer. Several years ago, he founded Icon Bioscience, his most ambitious effort yet in the area of sustained-release drug delivery.

He obtained initial funding for Icon from a number of private individuals who had done well with their investment in Oculex and believed that Dr. Wong could repeat that success at an even more complex level.

Using its patented Verisome technology as a basic platform, Icon has already developed more than 20 specific proprietary compounds that, in various combinations, can be formulated into drug-delivering solids, gels, semi-liquids and liquids. These vehicles, injected into the eye, can be tailored to deliver a drug for almost any length of time up to a year or more.

“At this point we still don't know the full potential of the Verisome platform,” says Dr. Wong. “It is the result of totally new research.”

Icon has two clinical trials currently underway. IBI-10090, which is injected into the anterior segment of the eye, is currently in a phase 1/2 trial. It is designed to deliver dexamethasone immediately following cataract surgery for the treatment of postop inflammation. The dose can be tailored to deliver the drug for a few days up to a month.

Another therapy, IBI-20089, is formulated to treat intermediate uveitis, delivering therapy over a six-month or one-year period. It is injected in the posterior segment as a gel and then forms a sphere, which degrades and eventually disappears as the drug is released.

FROM ACADEMIA TO INNOVATOR

Though he has successfully navigated the entrepreneurial culture of Silicon Valley for the past 20 years, Dr. Wong says that he is still “first, a doctor.” He concedes that the transition from academia to chairman and CEO has not always been an easy one.

“The way I look at it, it's like you are moving from one school to another,” he says. “To survive out here, you are going to have to embrace the Silicon Valley culture, but always first in my mind is how can I help people get better.” RP