Eyeworld

EW NEWS & OPINION 22 June 2015 by Vanessa Caceres EyeWorld Contributing Writer Envisioning the future of ocular drug delivery Ophthalmology lagged behind initially but now has many potential opportunities T he ophthalmologists of the future will likely have more drug delivery systems avail- able to them than just the old stand-by of eye drops. A sneak peek at upcoming drug delivery technologies Here is some more information on companies with innovative ophthalmic drug delivery approaches provided by sources for this article. This is just a sample and not a complete list of companies testing new drug delivery approaches. Envisia The company Liquidia spun out the company Envisia Therapeutics in 2013 to focus on a proprietary technology called PRINT that designs and manufactures micro- and nanoparticle systems. The technology enables designers to use precise particles of all sizes, shapes, and chemistry, including extended release formulations. Dr. Bloch, whose background as a physician is in radiology, likened the process to the printing of a newspaper. "They create these templates at a nanoscale and fill the tins with drugs and decorate them with different chemistries. It's a very flexible platform," he said. Envisia focuses this delivery approach within ophthalmology, and Liquidia uses this approach within pulmonary and for vaccines. GrayBug GrayBug, which was spun off from Wilmer Eye Institute at Johns Hopkins School of Medicine, focuses on micro- and nanoparticle extended release products for wet AMD and glaucoma. "The fast track is to establish business relations with companies that make the drugs but don't have the basis to deliver the drugs," Mr. O'Rourke said. Another goal is to take ophthalmic drugs that are off-patent and deliver them via the GrayBug platform, he added. Kala Pharmaceuticals Kala has developed a technology called mucous penetrating particles (MPPs) that can penetrate the body's mucosal barriers and reach the necessary therapeutic areas, providing a sustained, local concentration. Drugs delivered via MMPs can access areas that were previously only accessible via injections or implants. Clinical testing is underway with this approach to treat post-cataract surgery inflammation (phase 3), dry eye and blepharitis (phase 2), and retinal conditions like diabetic macular edema (phase 2), Dr. Pfefer said. The cataract surgery and dry eye/blepharitis deliveries involve the use of the steroid loteprednol etabonate. Kala is also seeking collaborations to use this same approach within disease treatment related to the lungs, female reproductive system, and the gastrointestinal tract. pSivida Already available in the clinical market is pSivida's Durasert, which is a miniature and injectable sustained-release drug delivery system, Dr. Ashton said. A Durasert product is in phase 3 clinical trials for uveitis; it has been licensed to Pfizer (New York) for a development-stage latanoprost product and to Alimera Sciences (Alpharetta, Ga.) for Iluvien (fluocinolone acetonide intravitreal implant), which is FDA approved for diabetic eye disease. pSivida has also designed a system called Tethadur Technology, which relies on nano-structuring. It can accommodate different molecule sizes and provide long-term delivery of antibodies and other proteins, according to the company website. Data on the use of Tethadur to release Avastin (bevacizumab, Genentech, South San Francisco) was presented at the 2014 Association for Research in Vision and Ophthalmology (ARVO) meeting in Orlando. However, it has taken a long time for the ophthalmic drug field to reach the point of drug delivery innovations. One major reason is the chal- lenge of engineering a delivery sys- tem that can penetrate the eye and reach exactly where it should, said Robert J. Noecker, MD, assistant clinical professor, Yale University School of Medicine, New Haven, Conn., and in private practice, Oph- thalmic Consultants of Connecticut, Fairfield. "The eye is very complex, and it's not a trivial exercise to dose properly in the eye," said Dr. Noecker, who also has a back- ground as a material scientist. "For some molecules, delivery via the eye or cornea is efficient. For other complex molecules, it can be very difficult to deliver them to the right place on the eye." Yet ophthalmologists and drug delivery innovators think the need for drug delivery methods beyond drops or injections like those used for wet age-related macular degener- ation (AMD) are sorely needed. First, there are the compliance problems with drops, which may be held by older patients who cannot steady their hands to accurately administer the drops—that is, if patients remember to use the drops in the first place. Second, there is a true need for sustained drug delivery, said Paul Ashton, PhD, president and CEO of pSivida, Watertown, Mass. For instance, the current antivascular endothelial growth factor injections used to treat wet AMD require pa- tients to return to the eye doctor ev- ery 4–6 weeks. "No one wants to get injected in the eye frequently," he said. His company is in pre-clinical stages of testing a 6-month sustained release of antibodies in the eye (see Eye drop installation Source: Robert Noecker, MD, MBA

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