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Implant could reduce risk of corneal graft rejection
A sustained-release drug implant could be the first therapy to receive FDA approval to treat patients at high risk of corneal graft failure.
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A novel sustained-release drug implant may create a new paradigm to reduce graft failure in patients receiving corneal transplants, according to a cornea specialist involved in its evaluation.
Francis W. Price Jr., MD, spoke with Ocular Surgery News about his participation in a clinical trial that is enrolling patients who are at high risk of graft failure. The trial seeks to test the efficacy of the implant, LX201, a silicone matrix ocular implant that steadily releases cyclosporine A locally for 1 year.
Currently, there is no treatment approved by the U.S. Food and Drug Administration for preventing corneal graft failure, according to Dr. Price, an OSN Cornea/External Disease Section Member. Historically, surgeons have used corticosteroids, but steroids have been shown to slow wound healing, he said. In addition, steroids have been associated with an increased risk of cataracts and elevated IOP, which can lead to glaucoma.
“Because they are not typically vascularized, corneal transplants are the most successful solid tissue [grafts], so we are expected to have good results. When we don’t, we really do not have anything else to offer these patients,” he said. “This is a tremendous opportunity to come up with something to help high-risk people so they also get good results with this surgery.”
Preventing graft rejection
Marianne Price, PhD, who is married to Dr. Francis Price and is director of research and education at the Cornea Research Foundation of America, announced the foundation’s participation in the international clinical trial.
“We had done a study a year and a half ago using cyclosporine eye drops to try to prevent graft rejection because it had been used systemically to prevent rejection of liver and kidney transplants,” she said.
However, cyclosporine is a large molecule that does not dissolve easily, making it difficult to achieve a high concentration in eye drops, she explained.
Meanwhile, Lux Biosciences had obtained the rights to use the LX201 implant.
“What is nice about it is it releases high concentrations right at the site, so we don’t have high systemic concentrations,” she said.
The trial will focus only on patients who are at high risk of corneal graft rejection, she said.
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Image: Price FW |
High risk
One-third of graft failures are attributable to graft rejection, Dr. Francis Price said.
Some corneal transplant patients are at low risk and others are at a higher risk, he added.
“Most graft failures occur within the first 2 years of surgery. They are not all immunological, but there is a good number that occur in that period of time, so our hope is to do something to knock down our initial rejection rate,” he said. “We think if we can get the eye nicely immunosuppressed in the first few months, we can minimize the chance of rejection later.”
Currently enrolling
Lux Biosciences announced in April that it had started treating patients in the LUCIDA (Lux Corneal Transplant Implant Development and Advancement of Therapy) clinical trial using its LX201 implant.
The device has received orphan drug status in both the United States and Europe, according to Lux Biosciences.
The company announced that it expects to enroll more than 400 high-risk patients at approximately 35 sites in North America, Europe and India.
Study details
The trial will include two controlled studies. The first study will enroll patients who are having a transplant and are at high risk of graft failure due to immunologic reasons, such as previous failed grafts, significant neovascularization of the cornea or a graft that is close to the limbus, Dr. Francis Price said.
Dr. Marianne Price explained that four out of five patients will receive the implants containing cyclosporine and one out of five will receive a placebo.
The second study is for people who have had a rejection episode with a corneal transplant within the last 6 months who could benefit from the implant to help prevent a recurrence. In this study, two-thirds of the patients will receive the treatment and one-third will receive placebo.
The LX201 implant will be sutured within the subconjunctival space and will release a steady dose of cyclosporine A, which is commonly used systemically to prevent kidney rejection.
Patients will be evaluated every 4 to 6 weeks for the first year, a period for which the device has been shown to deliver high concentrations of cyclosporine. In both of the studies, patients will use topical steroids, which will be tapered, for several months after the implantation.
“This trial will help us determine whether the implant provides an effective adjunct to standard treatment for providing corneal graft rejection,” Dr. Francis Price said.
For more information:
- Francis W. Price Jr., MD, can be reached at Price Vision Group, 9002 N. Meridian St., Suite 100, Indianapolis, IN 46260; 317-844-5530; fax: 317-844-5590; e-mail: fprice@pricevisiongroup.net.
- Marianne Price, PhD, can be reached at Cornea Research Foundation of America, 9002 North Meridian St., Suite 212, Indianapolis, IN 46260; 317-814-2990; fax: 317-814-2806; e-mail: mprice@cornea.org. Drs. Francis and Marianne Price are consultants for Lux Biosciences.
- Lux Biosciences, maker of the LX201, can be reached at Harborside Financial Center Plaza 10, 3 Second St., 14th Floor, Jersey City, NJ 07302; 201-946-0551; fax: 866-331-2790; e-mail: bd@luxbio.com; Web site: www.luxbio.com.
- Daniele Cruz is an OSN Correspondent based in Collingswood, N.J.