Up-and-coming glaucoma therapeutics and devices showcased

The glaucoma treatment market looks to receive a boost from new IOP-lowering and monitoring mechanisms.

Representatives from several companies at the Ophthalmology Innovation Summit presented an array of glaucoma therapeutics and devices that may change disease management.

“The glaucoma treatment market is unsatisfied and remains an attractive and dynamic market with the leading product, the prostaglandin analogue latanoprost, now available in generic form. It is a market that is highly receptive to innovation and clearly in need of new mechanisms that effectively lower IOP either as monotherapy or in combination with other agents,” Paul Howes, MBA, president and CEO of Inotek Pharmaceuticals, said.

Mr. Howes focused on Inotek’s new trabecular outflow enhancer, INO-8875. The drug is a highly selective subtype A1 adenosine mimetic that binds to the A1 receptors on epithelial cells in the trabecular meshwork, upregulating matrix metalloproteinase-2. This process is said to clean out the extracellular matrix, restoring outflow and lowering IOP.

“INO-8875 is a potentially transformative treatment for glaucoma and elevated IOP, which works by clearing the trabecular meshwork. It is safe and well-tolerated, both in the eyes and systemically, and adds IOP-lowering activity to multiple existing mechanisms,” Mr. Howes said.

The drug underwent 14 days of twice-daily dosing in a randomized, double-masked, placebo-controlled, phase 1b safety study with 70 healthy elderly volunteers. At high enough doses, IOP significantly decreased in eyes with baseline IOPs of 10 mm Hg to 13 mm Hg, suggesting a response potential over a wide range of IOPs and disease severities, Mr. Howes noted. Of the 42 participants exposed to INO-8875, only one experienced ocular hyperemia, lasting about an hour.

A locally or systemically intolerable dose could not be achieved, suggesting that the potential for overdosing is minimal. Phase 2 efficacy outcomes with Inotek’s commercial formulation are pending.

Additional therapeutics in pipeline

According to Thomas van Haarlem, MD, president and CEO of Aerie Pharmaceuticals, the company is currently developing a selection of internally discovered drugs that are expected to increase the number of treatment options available to glaucoma patients by offering novel drugs aimed at new targets with new mechanisms to lower IOP.

“Within 6 to 12 months, we will make substantial progress with this portfolio, having multiple products either in phase 3 or phase 2 clinical trials,” Dr. van Haarlem said.

Therapeutics under evaluation include ROCK inhibitor AR-12286, which is advancing to phase 3 trials based on good safety, efficacy and tolerability profiles and is also being developed as a fixed-dose combination of AR-12286 with travoprost. Early studies have shown this prostaglandin to have excellent additive efficacy and cause no excess hyperemia. A phase 2 trial to assess this combination is under way.

Aerie is also investigating a new class of potent ROCK inhibitors that are simultaneously aimed at a second new glaucoma drug target, the norepinephrine transporter. This newly discovered class of drugs may have the dual-action benefit of increasing outflow and decreasing aqueous production with a single once-daily eye drop. The lead candidate at present is AR-13324, and Aerie aims to initiate the first clinical study in early 2012.

Featured devices

In addition to up-and-coming glaucoma therapeutics, disease management may be further enhanced by new products that continuously measure IOP.

According to Jean-Marc Wismer, MSc, MBA, CEO of Sensimed, pressure behavior is highly dynamic, changing throughout the 24-hour daily cycle and varying by individual. This idiosyncratic behavior requires personalized treatment, and the Sensimed Triggerfish, a soft, hydrophilic, single-use contact lens, may accommodate such a need, Mr. Wismer said.

The lens is noninvasive and follows the eye’s shape, recording circumferential changes, which are directly proportional to changes in IOP. It contains passive and active strain gauges embedded in its silicone to monitor fluctuations in corneoscleral junction diameter.

“As IOP increases, the eye inflates, which flattens the [Triggerfish] contact lens. And in the lens, on the limbus, there is a strain gauge, which in turn is going to be stretched, and this we can measure easily. … It provides a full, 24-hour fluctuation profile to the doctor, which enables the doctor to do personalized management of glaucoma for the patient,” Mr. Wismer said.

Implandata Ophthalmic Products offers a permanent 24-hour IOP monitor to aid risk assessment and improve therapy and remote patient management. Max G. Ostermeier, CEO of the company, said that the system consists of a micro-sensor module in the form of a flexible, permanent implant delivering direct IOP monitoring that is placed either in conjunction with cataract surgery or during a stand-alone procedure, as well as a hand-held unit for easy measuring. IOP data can be integrated within a telemedicine infrastructure for remote patient management by the ophthalmologist.

Originally used in automotive applications, this technology enables automatic or semi-automatic telemetric pressure checks at any chosen cycle, allowing the patient to regularly measure IOP in the comfort of his or her own home, Mr. Ostermeier said. – by Michelle Pagnani

• Paul Howes, MBA, can be reached at Inotek Pharmaceuticals, 33 Hayden Ave., 2nd Floor, Lexington, MA 02421; email: phowes@inotekcorp.com.
• Max G. Ostermeier, can be reached at Implandata Ophthalmic Products, Vahrenwalder Strasse 7, 30165 Hannover, Germany; email: mostermeier@implandata.com.
• Thomas van Haarlem, MD, can be reached at Aerie Pharmaceuticals, 135 Route 202/206, Suite 9, Bedminster, NJ 07921; email: tvanhaarlem@aeriepharma.com.
• Jean-Marc Wismer, MSc, MBA, can be reached at Sensimed, Route de Chavannes 37, 1007 Lausanne, Switzerland; email: jean-marc_wismer@sensimed.ch.
• Disclosures: Mr. Howes is president and CEO of Inotek Pharmaceuticals. Mr. Ostermeier is CEO of Implandata Ophthalmic Products. Dr. van Haarlem is president and CEO of Aerie Pharmaceuticals. Mr. Wismer is CEO of Sensimed.