Several companies developing new pharmaceutical treatments for glaucoma are aiming to be the first to bring a brand new drug class into the therapeutic armamentarium since the first prostaglandin analogue was introduced 15 years ago. Industry representatives reported on their pipelines in a session co-moderated by Anthony P. Adamis, MD, Genentech, and Paul Chaney, PanOptica.
San Francisco-Several companies developing new pharmaceutical treatments for glaucoma are aiming to be the first to bring a brand new drug class into the therapeutic armamentarium since the first prostaglandin analogue was introduced 15 years ago. Industry representatives reported on their pipelines in a session co-moderated by Anthony P. Adamis, MD, Genentech, and Paul Chaney, PanOptica.
Rho-kinase (ROCK) inhibitors that lower IOP by directly reducing resistance to conventional outflow are under development at a number of companies. At Aerie Pharmaceuticals, the lead compound in this class, AR-12286, has completed phase II testing and is being readied for phase III investigation. In addition, a phase II study is under way investigating a fixed combination of AR-12286 with a prostaglandin analogue, said Thomas J. van Haarlem, MD, president and chief executive officer (CEO).
Simultaneously, the company is working on developing a new class of IOP-lowering medications that it discovered. These are “dual-action” drugs that act through ROCK inhibition and as norepinephrine transport inhibitors.
The dual-action drugs have an interesting efficacy and tolerability profile. Peak IOP reduction occurs late compared with other ROCK inhibitors and is of long duration. In addition, treatment-related hyperemia occurs early but disappears within a few days.
Dr. van Haarlem said IND filing is imminent for the lead compound in the dual-action class, and the company hopes to have the initial clinical data by the middle of 2012.
“Based on what we’ve seen in our animal testing, we might be looking at a new future standard of care in glaucoma,” he said. “We are also dreaming big, of combining this drug in a fixed combination with a prostaglandin analogue that would provide three mechanisms of action for IOP-lowering in a single drop, and we are continuing to work on new versions of this new class.”
Altheos Inc. is hoping the ROCK inhibitor it licensed from Asahi-Kasei Pharma, ATS-907, will be the best in class, said Henry Hsu, MD, CEO, Altheos.
ATS-907 has excellent and rapid cell penetration after administration, but after anterior chamber penetration, the parent prodrug is converted to a more active ROCK inhibitor that is less “cell penetrating” and so remains in the anterior chamber.
“It is hoped this profile will separate the site of action from the site of toxicity,” Dr. Hsu said.
So far, there are encouraging data from animal studies, and the company recently initiated a phase IIa clinical trial after receiving IND clearance.
Jack Elands, CEO, Amakem Therapeutics, said his company is also aiming to bring to market a ROCK inhibitor with a better therapeutic window, and it is approaching this goal based on the concept of localized drug action compounds that are rapidly inactivated.
The lead candidate, AMA0076, has been shown to cause no hyperemia when tested in a number of different animal models, and it has also demonstrated better efficacy than several other ROCK inhibitors and prostaglandin analogues in preclinical studies. It is now undergoing topical ocular and systemic toxicity studies, and IND filing is planned for the summer of 2012.
“We feel it is the first and only ROCK inhibitor that can be dosed to elicit maximal IOP lowering without causing hyperemia,” Elands said.
Isis Pharmaceuticals is focusing on the development of antisense therapeutics, and Scott Henry, PhD, vice president of non-clinical development, said this is a relatively unexplored area in glaucoma research, but one with a lot of opportunities.
One compelling aspect about using antisense technology for ocular therapeutics is the ability to apply the drug directly to the target site. In addition, studies to date show very favorable ocular kinetics with material administered by intravitreal injection having a very long residence time in the eye that would allow infrequent dosing.
Potential targets in glaucoma include improving glaucoma filtration surgery success, decreasing IOP, and neuroprotection, Dr. Henry said.
“Glaucoma is an important disease area for which antisense inhibitors can have an important role, adding both to mechanistic understanding and therapeutic interventions,” he concluded.
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