Monday, June 20, 2011

A Potential Breakthrough in the Treatment of Glaucoma

Three related news items caught my attention last week. They had to do with the medical treatment of glaucoma.

The first item noted that patients don’t properly use their prescription eyedrops in treating elevated intraocular pressure (IOP). Dr. Ari Weitzer, writing in his Eye Doc News Blog, noted that a retrospective hospital study in a recent issue of the Archives of Ophthalmology said that after 1 year, only 22% of patients were adhering to their glaucoma treatment regimen and putting drops in their eyes – and this dropped to 11% after 3 years. It turned out that this was a study done in Singapore on an Asian population, but similar studies done in the U.S. show similar patterns.

So, compliance with putting drops in the eye is a major ongoing concern. In an editorial, also in the Archives of Ophthalmology, Drs. Kelly Muir and Paul Lee noted that many patients (only 31%) were able to correctly install a single eyedrop. Approximately 20% of patients depend on another person to install their eyedrops.

The second item that caught my attention was that the cost of glaucoma treatment drugs has gone up strongly over the past six years, with spending on glaucoma medications increasing 25% over the period 2001 to 2006. Part of this is due to a change to newer, more expensive medications such as the prostaglandin analogs, which are now the most prescribed and popular drugs in use, compared to older types like the beta blockers. Also, the prevalence of glaucoma is rising as the U.S. population ages (and people live longer). By 2020, it is estimated that 3.4 million people are expected to be affected. Currently, some 2.2 million Americans aged 40 or older have primary open angle glaucoma and the annual direct medical cost is estimated to be $2.8 billion.

But, the third item that caught my eye may be the saving grace. In a news release on June 14th, pSivida announced the commencement of a Phase I/II clinical trial to study a new bioerodible drug delivery implant for the treatment of glaucoma and hypertension. The implant is designed to provide long-term sustained release of latanoprost, one of the new class of prostaglandin analogs. The drug delivery implant, based on the company’s Durasert technology system, will be injected into the subconjunctival space in the eye (between the sclera and the lower lid), be bioerodible and is expected to deliver its drug for a period of months.

If successful, this implant would solve the problems of non-compliance, the inability to administer the drops and, depending on its price, perhaps address the increasing cost issues.

The new dose-escalating study is designed to assess the safety and efficacy of the implant in patients with elevated intraocular pressure and with hypertension. If successful, pSivida plans to advance the product into a multicenter Phase II study.

A Little Background Information

The Treatment of Glaucoma

I first wrote about glaucoma in the fall of 2001. At that time I prepared a comprehensive overview of what glaucoma is, how it is diagnosed/detected, and both the medical and surgical treatment options available or under development at that time. I even included some information on the U.S. market sizes for both treatment and equipment. To read this report, Advances in the Treatment of Glaucoma, published by OptiStock, please follow this link.

Sustained Release Drug Delivery Systems

I have also, more recently, written an extensive overview of ophthalmic drug delivery systems in my article titled, Iluvien and the Future of Ophthalmic Drug Delivery Systems. This report describes the development of Alimera Science’s Iluvien which delivers a corticosteroid (fluocinolone acetonide – FA) to the retina for treating macular edema for up to three years. It is based on a drug delivery system developed by pSivida and licensed to Alimera for this application.

The report also discusses both FDA-approved sustained delivery drug systems as well as those still in development. One of the systems mentioned as under development was a latanoprost coated punctal plug to treat open-angle glaucoma, that was being developed by QLT Therapeutics. It was supposed to stay implanted and deliver its drug for up to three months. Apparently, the plug did not stay in place well and did not demonstrate efficacy and, to my knowledge, is no longer being evaluated.

The pSivida Latanoprost Implant

Some Background Information

In their press release, pSivida stated that this was a joint development with Pfizer Inc. Pfizer and pSivida have been working together on drug delivery technology since 2007, with Pfizer investing in the company and helping to fund research and development.

According to the press release, the insert is being developed under the recently amended Research and Collaboration Agreement with Pfizer Inc. Under the revised agreement, Pfizer will make an initial payment of $2.3 million. pSivida will, with technical assistance from Pfizer, have the right to develop the glaucoma product candidate through Phase II clinical trials. At that point, Pfizer may exercise its option for an exclusive, worldwide license to develop and commercialize the product candidate in return for a $20 million payment, double-digit royalty payments on any sales of the product and additional development, regulatory and sales performance milestone payments of up to $146.5 million. If Pfizer does not exercise its option, pSivida will retain the right to develop and commercialize the glaucoma product on its own or with a partner. As part of the amended agreement, pSivida regains all rights to its intellectual property in ophthalmic applications previously included in the original Research and Collaboration Agreement other than that required for the latanoprost implant.

Latanoprost, which was approved for use in the eye in 1996,  is now off-patent and low-cost generic forms of the drug are available.

Officials from both companies commented on both the new agreement and on the proposed new application of the implant to treat glaucoma and hypertension:

"Pfizer is an excellent partner, and we are pleased to be entering into this new stage of our relationship involving development of a potentially enhanced glaucoma product," said Dr. Paul Ashton, President and CEO of pSivida. "The $2.3 million payment from Pfizer comes on top of the approximately $7.0 million in R&D support we have already received from Pfizer since we first started our partnership in 2007. We believe that regaining rights to intellectual property in the ophthalmic arena outside the scope of the amended agreement is a key step for our company."

Yvonne Greenstreet, Senior Vice President and Head of the Medicines Development Group for Pfizer's Specialty Care Business Unit, added, "Latanoprost is the most commonly prescribed drug for reduction of intraocular pressure in the treatment of ocular hypertension and glaucoma. If successfully developed and approved by regulatory authorities, using pSivida's unique drug-delivery technology to deliver latanoprost could play a significant role in addressing compliance issues associated with a daily eye drop regimen for the treatment of glaucoma."

The Technology: How the Implant Will Work

The Durasert latanoprost implant (see Figure 1), is a tiny translucent cylindrical polymer tube, between 3 to 4 mm in length and about 0.4 mm in diameter, that contains a small amount of latanoprost (supplied by Pfizer). It is about the size of a grain of rice, and is designed to provide a low daily dose of latanoprost, which has a good history of treating open-angle glaucoma and hypertension.

Figure 1. The pSivida Durasert latanaprost implant.      

The implant will be injected into the subconjunctival space of a patient's eye (between the sclera and the lower lid – see Figure 2) using a proprietary insertion device. The implant is bioerodible and is expected to deliver an appropriate dosage of latanoprost for about three months and, depending on the results of the Phase I/II dosing study, might last as long as six months. Since the implant is bioerodible, it will be absorbed by the eye and will not have to be surgically removed.

Figure 2. Illustration showing conjunctival space where implant will be placed.

Latanoprost, now off-patent and available in generic form, is one of the class of prostaglandin analogs which  reduce pressure in the eye by increasing the outward flow of fluid from the eye. They generally work by relaxing muscles in the eye’s interior structure to allow better outflow of fluids, thus reducing buildup of eye pressure. According to glaucoma specialists, the prostaglandins have taken the lead in recent years as a first-line therapy for treating open-angle glaucoma.

Side effects may include eye redness or irritation, a change in eye color (mostly in hazel or green eyes), increase in thickness and number or eyelashes, and joint aches or flu-like symptoms.

The Phase I/II dose-escalating study is currently underway at the University of Kentucky.


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