Novel Drug Delivery Systems
A host of novel drug delivery systems that could stretch out intervals between injections are in human trials. In 2021, the FDA approved one such system, the refillable port delivery system (PDS) implant with ranibizumab (Susvimo). PDS is a small cylinder implanted into the eye and filled with 100 mg/mL of ranibizumab, to be released for 6 months or so, then refilled in the physician’s office when it’s empty.
But new implants of PDS were halted in 2022 after the manufacturer, Genentech, received reports the device leaked. Genentech said it has fixed those problems and confirmed the device should again become available for implants this year.
The most advanced novel drug delivery system in clinical trials is EYP-1901, a depot that contains the tyrosine kinase inhibitor (TKI) vorolanib. The depot is inserted under the ocular surface, where it biodegrades over 6 months as it releases the drug. A phase 3 trial is due to start enrollment at midyear.
An intravitreal implant with the TKI axitinib (Axpaxli) is in a phase 3 trial in nAMD and is due to start a phase 3 trial in diabetic retinopathy this year. At least four other implants, some of which biodegrade as they release the active ingredient, are in phase 1 or 2 trials.
TKIs themselves are a drug class worth watching in retina, said Jennifer I. Lim, MD, director of the retina service at the University of Illinois Chicago and president of the Retina Society.
“With TKIs, which activate intracellularly, in combination with anti-VEGFs will result in enhanced durability and possibly more efficacy for AMD,” Dr. Lim said. “TKIs in the phase 2 studies showed a marked reduction in the need for anti-VEGF injections in previously difficult-to-treat, high-need patient.”
Potential for Orals and Topicals
Topical eye drops are commonly used for anti-glaucoma drugs and antibiotics and corticosteroids for eye infections and inflammation, but using them for retinal disease has been a challenge. By the time the drug reaches the back of the eye, it has lost much of its pharmacokinetic activity. Three drops are in clinical trials for diabetic eye disease, with one, OCS-01, a preservative-free formulation of the corticosteroid dexamethasone, scheduled this year to enter a phase 3 trial.
At least four oral tablets are in early-stage human trials for diabetic eye disease. Four others are in clinical trials to treat geographic atrophy or early-stage dry AMD. They include tinlarebant, which is in phase 3 trials for geographic atrophy and Stargardt disease, an inherited retinal disorder.
Two other oral tablets are in human trials for inherited retinal disease. Like tinlarebant, emixustat has been in a phase 3 trial for Stargardt disease but showed no clinically significant improvement in macular atrophy. An early readout of an ongoing phase 2 trial of glideuretinol, a modified form of vitamin A, demonstrated slowed growth of macular atrophy in Stargardt.
These new and emerging treatments may potentially enable retina specialists to manage a rapidly growing aging population more efficiently, Dr. Sanders said.
“We have to figure out, on one hand, how do we catch the disease earlier? Like in other fields of medicine, the earlier you treat someone, the better,” Dr. Sanders said. “And also, how do we efficiently see these patients earlier to get therapy? Using implants or more durable drugs may be able to help us to treat more people more efficiently.”
Dr. Lim disclosed financial relationships with AbbVie/Allergan, Adverum Biotechnologies, Alimera Sciences, Bausch + Lomb, Chengdu Kanghong Biotechnology, Eyepoint Pharmaceuticals, Genentech/ Roche, Graybug Vision, Iveric Bio, Janssen Pharmaceuticals, Novartis, Regeneron Pharmaceuticals, RegenxBio, Santen, SparingVision, Stealth BioTherapeutics, Unity Biotechnology, and Viridian.
Dr. Boyer disclosed financial relationships with 4D Molecular Therapeutics, AbbVie/Allergan, Adverum Biotechnologies, Aldeyra Therapeutics, Alimera Sciences, Alkahest, Allegro, Amgen, Annexon Biosciences, Apellis Pharmaceuticals, AsclepiX Therapeutics, Aviceda Therapeutics, Bausch + Lomb, Bayer, Belite Bio, Clearside Biomedical, Eyepoint Pharmaceuticals, Genentech/ Roche, Graybug Vision, Iveric Bio, Janssen Pharmaceuticals, Nano scope Therapeutics, Novartis, Ocugen, Oculist, Ocuphire Pharma, Opthea, Pfizer, Regeneron Pharmaceuticals, RegenxBio, Sanofi, Stilbite Zhuhai, Stealth BioTherapeutics, Thea Laboratories, and Unity Biotechnology. Dr. Sanders had no relevant disclosures.
A version of this article appeared on Medscape.com.