But just as glaucoma is one of the most common eye-related conditions patients encounter – second only to age-related macular degeneration – a new therapy to address it is also one of the most significant medical business ventures to spring from Duke University.
The company is Aerie Pharmaceuticals. It went public in October 2013 and raised roughly $60 million. Its contribution to glaucoma treatment: once-daily eye drops that impact multiple disease factors.
“This is the first new class of drugs for the treatment of glaucoma in the last 25 years,” said Eric Toone, Ph.D., director of the Duke Innovation & Entrepreneurship Initiative. “And it’s about to go to market.”
Patients with glaucoma slowly lose their eyesight from the peripheral vision inward – opposite the inward-out progression experienced with age-related macular degeneration. Gradually, the trabecular meshwork that regulates approximately 80 percent of fluid drainage from the eye clogs, increasing the eye’s internal pressure. As a result, the optic nerve is damaged beyond repair.
Current eye drop medications relieve the pressure through the use of prostaglandin analogues – a lipid that controls muscle contraction and relaxation. . Prostaglandin analogues lower pressures by activating an alternate outflow pathway, not by curing the diseased tissue. And prostaglandins are linked to hyperemia, a condition where the eye whites turn red due to increased blood volumeRather than merely decreasing the pressure, Aerie’s products – Rhopressa™ and Roclatan™ — give patients a three-fold strategy to address the problems behind their symptoms.
The Aerie Difference
According to Toone, Aerie’s novel medications actively attack the problem areas that cause glaucoma. In doing so, the products fulfill the vision of the late David Epstein, M.D., Duke’s former chair of ophthalmology who was part of the team that brought Aerie to fruition.
“That was [David’s] big thing. You have to treat the diseased tissue,” said Toone, Professor of Chemistry and Professor of Biochemistry. “You treat the piece that isn’t working. He wanted a drug that solves that problem.”
Epstein, a renowned glaucoma expert, also served as the Duke Eye Center director.
Unlike existing medications, Rhopressa™ lowers pressures in a unique way, by facilitating the outflow of fluid through the eye’s primary drain, the trabecular meshwork, and it also reduces the blood pressure of the eye’s episcleral veins that are involved in draining eye fluid into the blood stream. In addition, it reduces the overall eye fluid production. If approved by the Food & Drug Administration (FDA), Rhopressa™ would be the only once-daily medication available that addresses these three problem areas.
Roclatan™ adds in a fourth capability already present in other glaucoma treatments. It uses the existing eye drop latanoprost to increase fluid outflow through the eye’s secondary drain point, the uveoscleral pathway.
Pathway to Duke
Although the clinical research and technology behind Aerie didn’t start at Duke, its imminent introduction to the industry is about to put Duke on the map of glaucoma care, said Toone, who is also an Aerie Pharmaceuticals founder.
The original research behind Aerie began at Proctor & Gamble (P&G) under the direction of Dr. Mitch DeLong and was focused on eliminating hyperemia by creating a more specific prostaglandin analogue. But, the work stalled, and the decision was made in 2006 to gift the entire venture to Duke, allowing its faculty to take control. Later, Dr. DeLong joined the Aerie team, and today is Aerie’s Vice President of Chemistry R&D.
The early medical chemistry development occurred in Toone’s lab. Later, the team discovered the answer to alleviating eye pressure, he said, lay in the cytology of the trabecular meshwork. On microscope slides, they could determine that a new class of drugs – rho-kinase inhibitors – prompted the meshwork cells to shrink and allow for more fluid outflow. The lead compound was actually found in a chemical library belonging to another Duke start-up – and specifically affected the meshwork and not the secondary uveoscleral pathway.
Along the way, biotechnology consultant Casey Kopczynski joined the team and was Aerie’s third scientific founder. Kopczynski now serves as Aerie’s chief science officer. Together, Toone, Epstein and Kopczynski worked to secure a $25 million venture financing, an amount that funded the research and supported the company past the Phase I clinical trial and into Phase II. The company’s IPO provided the financing necessary to advance both drugs through Phase III trials.
Currently Phase III trials are underway in both the United States and Canada to test the efficacy and safety of Rhopressa™ in reducing inner-eye pressure when compared to timolol, the current glaucoma treatment on the market. These study results, along with the Phase I and II safety and efficacy trial results, will factor into whether the FDA will grant Aerie approval.
The next step, Toone said, is patient accessibility.
“If the trials go well,” he said. “The expectation is that the drug will be brought to market by the first half of 2016.”