On the Forefront

Sirion Therapeutics Developing Promising Treatments for Retinal Diseases

Sirion Therapeutics, a biopharmaceutical company based in Tampa, Florida, has three promising drugs for the treatment of retinal degenerative diseases in its development pipeline. Two are oral medications that may provide treatment for retinal diseases that are caused by the accumulation of toxic deposits in the retina, such as dry agerelated macular degeneration (AMD), Stargardt disease, and Best disease.

A third drug is a topically applied medication that has anti-oxidative properties, and is currently being investigated for AMD. It may also be effective for treating a variety of other retinal degenerative diseases.
The three compounds are:

Fenretinide — In spring of 2009, Sirion is planning to release one-year results of a Phase II clinical trial of fenretinide for the treatment of dry AMD. A total of 245 patients were enrolled in the study (recruitment is complete). If the drug is shown to be effective, Sirion hopes to continue development into the next phase of clinical testing. Results from future trials will be used for submission to the FDA for drug approval. If the therapy proves to be effective and safe, FDA approval could be achieved within the next 2.5 to 3.5 years.

In preclinical studies, fenretinide reduced the accumulation of lipofuscin in a layer of the retina known as the retinal pigment epithelium. Lipofuscin is comprised of toxic compounds which are known to cause retinal damage and vision loss.

Fenretinide was also found to be effective in a Foundation-funded preclinical study employing an animal model of Stargardt disease.

Nathan Mata, Ph.D., Senior Vice President of Discovery Research and Chief Scientific Officer at Sirion, says that if fenretinide is effective for the treatment of dry AMD, it is likely to be beneficial in the treatment of other retinal diseases — such as Stargardt and Best diseases — which are characterized by excessive accumulation of lipofuscin.

Prior clinical studies have established fenretinide’s long-term safety and tolerability. The studies also determined that fenretinide is teratogenic (not appropriate for women of child-bearing age).

SIR-1047 — Currently in preclinical development, SIR-1047 is an oral medication which has greater potency than fenretinide. Also, SIR-1047 is not expected to be safe for women of child-bearing age. Depending on the results of preclinical safety studies, Sirion hopes to obtain FDA approval to begin a Phase I safety study of SIR-1047 in fall 2009. If the drug performs well in clinical studies, it could be approved for sale in the USA in about six years.

Dr. Mata says that this medication has shown remarkable efficacy in the Stargardt animal model. Like fenretinide, SIR-1047 is expected to be effective for the treatment of dry AMD, Stargardt disease and Best disease. He says, “Conceivably, patients would not have to take as much of SIR-1047 as fenretinide to get the same therapeutic benefit.” Furthermore, he notes that if SIR-1047 is shown to be free of teratogenicity, it might be more appropriate for younger patients with retinal diseases.

SIR-1076 — Also in preclinical development is SIR-1076, an eye drop that shows promise in reducing oxidative stress, which has been implicated in a wide range of retinal diseases including AMD and retinitis pigmentosa. Sirion will initially evaluate SIR-1076 for reducing the risk of progression of dry and wet AMD.

Dr. Mata says, “Animals treated with SIR-1076 eye drops had a dramatic reduction in biomarkers of oxidative stress within the retina. We are confident about the ability of this compound to do what we want it to do.”

Sirion hopes to begin clinical studies of SIR-1076 for AMD by 2010. Pending successful clinical outcomes, the drug could be FDA approved within six years.