at press time

Xalatan Marks 10th Anniversary
Prostaglandin Glaucoma Medication Overcame Obstacles.

Though Xalatan (latanoprost) was approved by the FDA in 1996 and became the first worldwide prostaglandin analogue for the medical treatment of glaucoma, the roots of this pioneering therapy go back to the mid-1970s and the experiments of a Yale undergraduate.

That was when Carl B. Camras and his mentors decided to test a theory that the IOP-lowering effectiveness of epinephrine, then a commonly used glaucoma medication, could be improved by binding it to glass beads. Young Camras began implanting the epinephrine-coated beads in the eyes of rabbits.

Camras' experiments led him to an interesting discovery.

Though the rabbits' eyes became red and inflamed, their IOP was dramatically reduced and the improvement was sustained for long periods regardless of whether the beads were coated with epinephrine.

"At that time, the thinking was that prostaglandins were a bad thing because they were associated with inflammation," says Camras, now an ophthalmologist who serves as professor, chairman and director of the glaucoma service in the Department of Ophthalmology and Visual Sciences at the University of Nebraska Medical Center in Omaha. "But if the prostaglandins were responsible for the inflammation, they might also be responsible for the sustained IOP reduction we observed."

As a medical student at Columbia University, Camras found a kindred spirit and mentor in Laszlo Bito, Ph.D., who came to share similar ideas concerning the potential therapeutic value of prostaglandins. They started to think that it might be possible to separate the IOP-lowering properties of prostaglandins from the inflammatory properties and were eventually able to find a formulation that produced significantly lowered IOP with a minimum of inflammation in animals.

Pharmacia was intrigued enough to acquire an existing patent. Pharmacia researchers began to test hundreds of compounds in an effort to find a prostaglandin formulation that did not produce negative side effects. The compound that Pharmacia eventually selected for further study was latanoprost.

After a trio of pivotal phase 3 clinical trials were conducted in the early to mid-1990s, the FDA approved Xalatan in 1996. Dr. Camras served as the lead investigator for the U.S. phase 3 trial.

"When Xalatan was approved, beta-blockers were the most commonly used medical treatment for glaucoma," says Dr. Camras. "Though Xalatan was quickly adopted as first-line therapy by many glaucoma specialists because it is more effective and doesn't cause systemic side effects, it took several years for the drug to become the market leader."

According to Pfizer, which acquired Pharmacia in 2003, more than 19 million new prescriptions have been written for Xalatan in the 10 years since its approval.

Today, several other prostaglandin analogues are also available for the treatment of glaucoma.

STOCK WATCH
A LOOK AT THE PERFORMANCE OF OPHTHALMIC COMPANIES

IN THE NEWS

►Lucentis wins approval. Following a 6-month Priority Review, the FDA has approved Genentech's Lucentis for the treatment of wet AMD. The FDA attached no major restrictions on Lucentis use.

Lucentis is an intravitreally injected antiangiogenic that inhibits Vascular Endothelial Growth Factor (VEGF), which is believed to be largely responsible for the formation of unwanted new blood vessels in the eye.

Lucentis joins Macugen and Visudyne as FDA-approved therapies for the treatment of wet AMD, though a number of other potential treatments are currently being investigated and a Genentech cancer drug, Avastin, has increasingly been used "off-label" to treat wet AMD. (see "Sorting out the Wet AMD Treatments on page 55).

Approximately 95% of patients treated monthly with Lucentis maintained their vision in two pivotal phase 3 clinical studies. Vision improved by at least 15 letters on the study eye chart in up to 40% of these patients at 1 year.

"Lucentis provides new hope for patients with wet AMD because it is the first therapy to provide a benefit in vision for a significant number of patients," said Arthur D. Levinson, Ph.D., Genentech's chairman and CEO.

"In my opinion, the Lucentis approval stands out as one of the most important medical developments in ophthalmology during my 25 years in the field because it has the potential to reverse vision loss associated with wet AMD," said Eugene de Juan, M.D., president of the American Society of Retina Specialists. "We are pleased that Lucentis has been approved by the FDA and look forward to working with Genentech to provide retina specialists in the United States with access to Lucentis for patients as quickly and smoothly as possible."

The Lucentis 0.5 mg dose is recommended for intravitreal injection once a month. If monthly injections are not feasible, treatments can be reduced to one injection every 3 months after the first four monthly injections. However, recently released results of Genentech's PIER study indicate that dosing every 3 months will lead to an approximate five-letter loss of visual acuity benefit, on average, over the following 9 months. Some retina specialists are now using OCT measurements to determine when retreatment is needed. In the investigator-sponsored PrONTO study using OCT measurements to determine the need for retreatment, patients required an average of 5-6 injections a year to maintain the maximum benefit of Lucentis.

"Now that Lucentis is approved, we will continue to work with the retina community to evaluate how patients may be able to benefit from less frequent dosing, as emerging clinical data indicate that dosing may need to be tailored to individual patient needs," said Levinson.

►First-line for Lumigan. Allergan said the FDA has approved its once-daily prescription eye drop Lumigan as a first-line treatment for elevated IOP associated with open-angle glaucoma or ocular hypertension. The first-line indication is in addition to Lumigan's widely established use as a second-line treatment.

►ISTA files for T-Pred. ISTA Pharmaceuticals, Inc. said the company has filed a New Drug Application (NDA) with the FDA for its investigational ophthalmic product, T-Pred, containing tobramycin and prednisolone acetate in a fixed combination. T-Pred is a treatment for inflammatory ocular conditions for which a corticosteroid is indicated and where bacterial ocular infections or a risk of bacterial infections exists.

According to 2005 IMS Health data, prednisolone acetate is the most prescribed ophthalmic steroid and tobramycin is the most prescribed aminoglycocide antibiotic solution by ophthalmologists in the United States.

"If approved, we believe T-Pred will offer patients a powerful new treatment combining fast anti-inflammatory relief with excellent anti-bacterial coverage," said Vicente Anido, Ph.D., president and CEO of ISTA Pharmaceuticals. "Pending acceptance and timely approval of our T-Pred NDA submission, we anticipate a potential launch of this product in mid-2007."

►NDA files for anti-infective. InSite Vision Inc.,an ophthalmic products company currently developing therapies that treat ocular infection, glaucoma and retinal diseases, announced it has submitted an NDA for AzaSite for the treatment of bacterial conjunctivitis. AzaSite combines a topical 1% azithromycin formulation with InSite's patented DuraSite ophthalmic drug-delivery system that increases ocular retention of the drug.

►ISTA adds to pipeline. ISTA Pharmaceuticals said it has exclusively licensed from Senju Pharmaceuticals, Co., Ltd. the North American rights to two new product candidates, iganidipine, a calcium channel blocker, and a new formulation of latanoprost, a prostaglandin analogue. Both are under investigation for the treatment of glaucoma and other ophthalmic applications, and, if approved, will be complementary to Istalol, ISTA's once-daily beta blocker, currently marketed for the treatment of glaucoma.

►Sirion to develop anti-inflammatory. Sirion Therapeutics, Inc., an ophthalmic-focused pharmaceutical company, said it has reached an exclusive licensing agreement with Senju Pharmaceutical Co., Ltd. of Japan for the U.S. rights to develop and market a topical ophthalmic emulsion containing the steroid compound difluprednate for the treatment of inflammatory eye diseases.

Sirion Chairman and CEO, Barry Butler, said the company expects to file an Investigational New Drug application by the end of 2006, and plans to begin phase 3 trials in the United States during the first half of next year.

GIVING BACK:Advancing Iraq's Medical Community
Dr. Michael Brennan: Envoy for Progress.
By John Parkinson, Associate Editor

In the summer of 2003, ophthalmologist Michael W. Brennan, M.D., received a call from an old West Point friend who was the army surgeon general. His friend asked Dr. Brennan, who was then retired from the army, to work with the American military on a mission called Iraqi Military Medical Specialty Forum.

Dr. Brennan, along with a military physician and an Iraqi orthopedic surgeon, were to facilitate reconstitution of 16 to 20 specialty organizations and convene a leadership conference with physician leaders from all over Iraq within 2 months. Six months later they were to hold a formal forum for physicians in general.

Dr. Michael Brennan (far right) with Iraq's medical specialty task force at a meeting in Kurdistan.

With the support of his family and practice partners in Burlington N.C., Dr. Brennan departed on his first mission to Iraq. Baghdad was the starting point because much of the country's medical education centers and specialty hospitals were there. Dr. Brennan spoke to physicians and educators about standardizing education, establishing practice patterns, modernizing infrastructure and conducting outreach to the international medical community. He also traveled to other regions of Iraq to speak with specialists in an attempt to gauge their interest in developing national societies within their subspecialties.

"What we were attempting to do was form trustful, personal relationships with Iraqi physicians and see if we could find some common objectives," he says. Dr. Brennan tried to initiate dialogue within the physician community without giving the appearance he was forcing an American agenda. He also stressed the importance of establishing non-governmental medical leadership.

After his first trip, which lasted more than 2 months, Dr. Brennan came home and reached out to the American Medical Association and the Council of Medical Societies, asking for volunteers from every subspecialty. He went back to Iraq in the spring of 2004 with approximately 25 American physicians from various subspecialties and conducted a successful 5-day forum with approximately 500 Iraqi physicians in Baghdad. Military medicine leaders supplied extensive organizational and communications support for the volunteer physicians known as the Medical Alliance for Iraq (MAI).

Out of that forum, Dr. Brennan thought progress was being made toward the formation of an Iraqi medical association. However, since that last trip, some of the new programs that had been established, such as accreditation of medical colleges, standardization of residency training and a system of board certification, have encountered delays. In addition, plans for another meeting scheduled for earlier this year fell apart. Dr. Brennan says the country's destabilization, along with mistrust between ethnic groups, has made progress difficult.

"We are waiting for the environment [in Iraq] to cool off a bit, but we are still in touch with our [Iraqi] colleagues," he notes.

He remains optimistic and points to rescheduled meetings with the Iraqis to be held in northern and southern Iraq in December. Dr. Brennan is also getting acquainted with the newly appointed Ministers of Health and Education to establish regional educational medical centers in Iraq.

"We would be responsive to the Minister of Health's priorities — primary care, nursing, emergency medicine," says Dr. Brennan. "We would be sensitive to the Minister of Education's standards for accreditation, assessment and certification, so that these centers could run under a systematic basis. We would pledge to provide international faculty."

Dr. Brennan, members of the MAI and United Kingdom volunteers are also hoping to meet cadres of general practitioners to teach them skills such as primary eye care and primary ear, nose and throat medicine.

Dr. Brennan has enjoyed his work in Iraq, and suggests other physicians get involved with diplomacy roles. "There are volunteer opportunities in medicine that aren't just clinical," he notes.

WORTH NOTING

►Eyemaginations names COO. Eyemaginations, Inc. has appointed Joseph Boorady, O.D., as chief operating officer. Dr. Boorady joins Eyemaginations from his position as vice president for clinical affairs and executive director of the University Optometric Center at the SUNY College of Optometry.

Dr. Boorady will be responsible for key business development initiatives as well as day-to-day operations, with his primary focus on developing and enhancing the infrastructure of a company experiencing dramatic expansion.

Eyemaginations is the leading creator of interactive patient education and practice management communications for ophthalmologists and optometrists.

►Settlement in patent case. Advanced Medical Optics (AMO) and Alcon have reached a comprehensive settlement resolving all pending patent infringement lawsuits between the companies on technologies used in ophthalmic procedures.

Under the agreement, Alcon will pay AMO a lump sum of $121 million. The parties agree to dismiss all existing patent litigation and not to sue on the patents at issue, including the use of multiple viscoelastics in one surgical procedure. In addition, each company is granted a license to the patents covering its existing phacoemulsification equipment features, which allows them to market their current products without the threat of litigation.

►Sykora named. Robert "Bob" Sykora, R.Ph., was recently named president of StoneBridge Pharma, LLC, a newly created position in which he will be responsible for all daily operations, strategy and business development activities for the Georgia-based specialty pharmaceutical company. StoneBridge develops products and medical devices for use in ophthalmology, gastroenterology and women's health.