At Press Time

ISTA Pharmaceuticals Makes Steady Progress

Aiming for Profitability by 2009.

By Jerry Helzner, Senior Editor

■ The moral of the legendary fable of the tortoise and the hare is that "slow and steady wins the race." ISTA Pharmaceuticals appears to be successfully following that philosophy with a goal of bringing a new or improved ophthalmic drug to market every 12 to 18 months.

The company, based in Irvine, Calif., and relaunched in 2002, is led by an experienced management team, many of whom previously worked at Allergan. With total sales expected to approach $60 million in 2007, management believes ISTA can become profitable by 2009 and reach $200 million in sales by 2011. ISTA limits its marketing efforts to the United States, the world's largest market for ophthalmic drugs.

Focusing primarily thus far on eyedrop products for the anterior segment, ISTA has already commercialized Vitrase, a spreading agent for ophthalmic surgery; Istalol, a once-daily formulation of timolol for glaucoma, and Xibrom, the only NSAID with a twice-daily dosing schedule. Far along in clinical trials are T-Pred, a combination anti-inflammatory, anti-infective for ocular inflammation accompanied by the presence or threat of infection; Bepreve for ocular allergies and ecabet sodium for dry eye. Further back in the pipeline are a strong steroid for ocular inflammation, a new formulation for the glaucoma drug latanaprost, which comes off patent in 2011, and a calcium channel blocker, also for glaucoma.

Xibrom is currently ISTA's flagship product, accounting for approximately 70% of the company's sales in 2007. Xibrom has been a major success for the company, having increased its market share (in dollars) by 6.6 percentage points in the 12 months ending November 2007. Xibrom is now the second most widely prescribed NSAID among U.S. ophthalmologists with a market share of 28.8%.

Lauren Silvernail, ISTA CFO and director of corporate development, believes Xibrom's market share will move even higher when the company obtains FDA approval for a once-daily formulation of the drug. Competing NSAIDs currently require three or four doses daily.

"We anticipate approval of this formulation in 2008," says Silvernail. "We think going to once-a-day will really shift the paradigm."

Thus far, ISTA has been able to fund its own clinical trials with financing primarily provided by the public markets and venture capital firms, such as New Leaf Venture Partners and The Sprout Group. New Leaf has an approximately 20% ownership stake in ISTA. Having access to these deep pockets has allowed ISTA to move ahead without taking on major pharmaceutical companies as partners.

The well-measured pace of ISTA's progress encountered an obstacle in May 2007 when the FDA gave the firm a "non-approvable" letter for T-Pred, which, if approved, would compete with two other fixed-combination drugs, Zylet and Tobradex.

"The non-approvable letter is definitely a negative," says Silvernail, "but we are in discussions with the FDA regarding the future of T-Pred."

One possibility is that the FDA will require another clinical trial for T-Pred.

Silvernail says ISTA develops therapies that can enjoy a significant advantage over existing competition. She points out that Xibrom is a "potent molecule" that can be efficacious with fewer doses than competing drugs. Bepreve, which would compete with Alcon's Patanol and Pataday once approved, offers an early onset of action and has also been shown to alleviate nasal symptoms. Ecabet sodium (no brand name yet) is well-tolerated and could be an alternative for patients who do not react well to the dry eye drug Restasis.

"Ecabet sodium could also be used as a complement to Restasis because it has a different mechanism of action," notes Silvernail.

With a well-planned approach to its marketplace, ISTA's management leaves little to chance. In fact, the only puzzle to outsiders is the derivation of the company's own name: ISTA.

Puzzle solved: ISTA means "eye" in Lakota, the language of a native-American people of the plains. OM

Giving Back: Taking ORBIS to a New Level

Dr. Helveston Heads the Organization's Cyber-Sight Program.

By Jerry Helzner, Senior Editor

■ After 40 missions on the plane and on the ground to all corners of the globe as an ORBIS International volunteer, Eugene M. Helveston, M.D., is now heading an initiative that allows ophthalmologists to make an important contribution to the advancement of worldwide eye care without ever having to leave the comfort of their own homes.

Dr. Helveston, 73, the emeritus professor of ophthalmology at the Indiana University School of Medicine and a much-honored pioneer in the field of pediatric ophthalmology, got the idea of establishing Internet-based consultations in 1998 after a mission to Havana.

"On my first visit, the Cuban doctors had such poor instruments that I could not perform the procedures that had been planned," says Dr. Helveston. "I went back with a set of instruments, performed the operations, and then set up an informal e-mail system to share information and clinical photos with these doctors. It worked out very well and we were able to improve outcomes. Later, I was able to expand the program to Romania, Albania and the Dominican Republic."

Following those initial successes, a private donor gave Dr. Helveston $150,000 in seed money for a telemedicine initiative. ORBIS took over the program in 2002 with Dr. Helveston as the director. The initiative, now called Cyber-Sight, also received a $250,000 corporate donation to expand the initiative worldwide.

"To date, we have held more than 4,000 consultations and transferred approximately 35,000 photos through our Web site, www.cybersight.org," notes Dr. Helveston. "We have 140 volunteer ophthalmologists, with 40 to 50 doctors actively consulting via Cyber-Sight. Ophthalmologists from all over the world can receive advice from our mentor ophthalmologists, within hours if the consultation request is sent as 'urgent.'"

Dr. Helveston with a young patient during a mission to Libya.

Though Cyber-Sight now stands as one of the three primary ORBIS initiatives, along with airplane-based and hospital-based eye care, Dr. Helveston's association with the organization did not start on a high note. He missed out on a 1983 mission because of a mechanical problem that canceled his commercial flight to Uruguay.

In 1985, Dr. Helveston completed his first successful mission for ORBIS, this time to Jamaica.

"I went to Jamaica as a pediatric ophthalmologist," he says. Over the ensuing years, Dr. Helveston was instrumental in establishing pediatric ophthalmology as an essential activity of the ORBIS concept.

"Starting in 1985, I went on at least one mission a year, usually with my wife Barbara. I was 50. We were at a point in our lives when we had the freedom to do more of these missions."

Dr. Helveston says that several of his many missions stand out as being particularly challenging.

"We were in Russia in 1987 at the end of the Soviet regime," he recalls. "They had some facilities with the absolute latest technology but they were doing RK using the same knife on every patient. They had no apparent concern for sterile techniques. It was bizarre. And their research data was concocted to make their system look good."

In China, Dr. Helveston had planned on performing a trabeculotomy on a young glaucoma patient but the case proved to be difficult and in mid-procedure he quickly adjusted and performed a trabeculectomy.

"The host doctors did not approve because in their culture it seems that if you say you are doing X you cannot change your plan and do Y even if it is indicated by findings at the time."

He also found it difficult to elicit questions from some overseas ophthalmology students because they thought it disrespectful to question a teacher.

Dr. Helveston says the biggest challenge that ORBIS faces today is creating missions that move from helping the few to helping entire societies.

"We can train local doctors but there have to be government support programs in these countries that make it possible for the local doctors to stay and treat their people. Many ophthalmologists in developing countries are just not compensated properly for their skills and efforts."