A review of IOP-lowering treatments under evaluation

When managing patients who have any sight-threatening disease, educating them about ongoing efforts in research and development for new treatments and a cure provides much needed hope. Further, when you provide this information, it builds confidence in your expertise regarding their treatment. With all this in mind, this month’s column is dedicated to glaucoma-related treatments in the pipeline.

TOPICAL DRUG

Netarsudil 0.02% latanoprost 0.005% (Roclatan, Aerie Pharmaceuticals) is dosed once daily. It is believed to lower IOP through enhanced trabecular meshwork outflow, decrease in aqueous production, increase in uveoscleral outflow and the reduction of episcleral venous pressure.

Roclatan demonstrated statistical superiority over both its components in MERCURY 1 (a 12-month Phase 3 trial) and MERCURY 2 (a 90-day Phase 3 trial) at all nine time points measured, producing incremental IOP-reduction of 1 mmHg to 3 mmHg over latanoprost and netarsudil alone. In MERCURY 1, 60% of patients achieved a mean diurnal IOP of 16 mmHg or lower at month 12, compared to 35% for latanoprost and 37% for netarsudil. The most common side effect, in approximately 60% of patients, was conjunctival hyperemia, which the majority scored as mild and sporadic.

The combination drug is un- dergoing FDA review with the PDUFA goal date for completion March 14.

DRUG DELIVERY

Three drug-delivery systems aim to overcome the side effect of glaucoma-drop-caused ocular surface disease and can aid in increasing patient adherence.

1. Bimatoprost ocular ring insert (Allergan). Flexible and available in various sizes from 24 mm to 29 mm in diameter, the Ring, composed of a polymer-bimatoprost matrix, rests on the ocular surface under the eye lids. It releases clinically effective concentrations of preservative-free bimatoprost over several months.
   In a Phase 2 study, published in Ophthalmology, the ocular insert demonstrated IOP lowering of 4 mmHg to 6 mmHg, 93% and 89% retention of the Ring after 12 weeks or six months of wear across all treatment groups, and the most common adverse events in patients treated with the Bimatoprost Ring were eye discharge (16%) and conjunctival hyperemia (14% of patients)1. In a 13-month extension to the Phase 2 study, Rings were maintained in place in 95% of patients, and the most common adverse events were, again, eye discharge and conjunctival hyperemia (21% of patients each), with the majority of those patients scoring mild.
   Allergan’s Phase 3 clinical trial development with the Bimatoprost Ring is in progress.
2. Travoprost intracanalicular insert (OTX-TP, Ocular Therapeutix). This may reduce IOP connected to glaucoma and ocular hypertension for up to 90 days with a single preservative-free administration.
   Proprietary hydrogel technology is engineered for OTX-TP to deliver a sustained release dose of travoprost, which will then resorb through bulk hydrolysis and exit through the nasolacrimal system.
   In a Phase 2 trial, mean IOP reduction from baseline in the OTX-TP group was clinically relevant at all 13 time points, with reductions ranging from 2.30 mmHg to 5.68 mmHg. There were no notable observations of clinical relevance among the slit-lamp biomicroscopy assessments, including differences in ocular hyperemia scores.
   OTX-TP is currently in Phase 3 clinical trials.
3. Silicone punctal plug-based system (Evolute, Mati Therapeutics). This is comprised of a non-biodegradable punctal plug delivery system with a drug-eluting core that delivers medication to the tear film. It is sealed along the sides and at the distal end, to minimize potential systemic absorption in non-targeted tissues.
   A total of 3.9% of patients who have used it reported conjunctival hyperemia.
   In Phase 2 clinical trials, the system demonstrated IOP lowering of 5 mmHg to 6 mmHg and a plug retention of 92% to 96%.
   No information was available on the insert’s status.

HOPE

We have already seen many drugs come to fruition, most recently netarsudil 0.02% (Rhopressa, Aerie Pharmaceuticals) and latanoprostene bunod 0.024% (Vyzulta, Bausch + Lomb). We will, no doubt, have another glaucoma drug to add to our treatment armamentarium, with the recent FDA approval of the NDA for latanoprost ophthalmic emulsion 0.005% (Xelpros, Sun Pharma). Hope springs eternal. OM

Special thanks to Leslie E. O’Dell, O.D., F.A.A.O., for reviewing this column.

DR. SCHWEITZER specializes in advanced glaucoma, refractive surgical clinical care and anterior segment pathology at Vance Thompson Vision. He has had multiple articles published and has delivered lectures on glaucoma, anterior segment pathology, refractive surgical clinical care and surgical management. Email him at justin.schweitzer@vancethompsonvision.com.