OR WAIT null SECS
By Fred Gebhart
Ophthalmologists have been waiting nearly 20 years for new molecules with novel mechanisms of action (MOA) to treat glaucoma. That long drought could be over by the end of 2016.
“As a clinician, I am hungry for another alternative to treat glaucoma,” said Eydie Miller-Ellis, MD, professor of clinical ophthalmology and director of glaucoma services at Scheie Eye Institute/University of Pennsylvania, Philadelphia. “Hardly a day goes by that a patient doesn’t ask me what’s new, what’s next, isn’t there anything else you can do for me? The day appears to be coming when I will be able to tell them ‘yes,’ there is something new.”
Watch as Gary Novack, PhD, of PharmaLogic Development outlines the state of glaucoma pharmaceuticals.
Dr. Miller-Ellis made that optimistic prediction as she introduced two companies moving toward their initial NDA submissions during the “New Horizons in Glaucoma Pharmaceuticals” session. Aerie Pharmaceuticals expects to file its first NDA in mid-2016. Valeant/Bausch + Lomb plans an NDA submission during the second quarter of 2015.
“With a plethora of generic therapeutics, the need for novel MOAs that can perform against the escalating co-pays and controls over access to show that these drugs mean something to patients in terms of their vision is very challenging place to be,” said Paul Chaney, president and CEO of PanOptica. “These two companies are getting closer.”
Chaney co-moderated the session with Dr. Miller-Ellis.
Listen as Aerie Pharmaceuticals and Valeant/Bausch + Lomb present their latest glaucoma drugs in development.
Latanoprost hit the U.S. market in 1996, the last new glaucoma agent with a novel MOA. The first novel MOA to reach market since latanoprost could be a related compound, latanoprostene bunod (LBN). The new agent is a nitric oxide-donating prostaglandin F2α receptor agonist that is rapidly metabolized in situ to latanoprost acid and BDMN, an NO-donating moiety.
Latanoprost acid uses the classic latanoprost pathway to enhance uveoscleral outflow, said Baldo Scassellati Sforzolini, MD, vice president of eye care at Valeant. BDMN donates NO, a key signaling molecule that enhances tissue relaxation and improves outflow through the trabecular meshwork. The NO pathway gives LBN a statistically and clinically significant advantage over latanoprost and other IOP-lowering agents.
Animal models showed LBN lowers IOP in animals that are non-responsive to prostaglandins via NO activity. A total of nine clinical trials in Europe, Japan, and the United States have shown uniformly positive results compared to both latanoprost and timolol over a 24-hour period with once-daily topical application.
In what Valeant hopes will be two pivotal phase III studies LBN, which met its primary endpoint, non-inferiority to timolol, and showed superior IOP lowering compared to timolol with no increase in hyperemia or other adverse events. The agent is subject to all the familiar adherence pitfalls associated with eye drops, but is more effective than other drops in lowering IOP.
“We have a drug that is very effective in reducing IOP without the increase in hyperemia that is seen with some of the competitors to latanoprost,” Dr. Sforzolini said. “We believe we have the most effective, IOP-lowering monotherapy to date and we are on track for an NDA submission during the second half of 2015.”
Aerie is developing two glaucoma drugs with multiple MOA in a single medication. The most advanced candidate, Rhopressa, hits IOP from three different angles. Look for release of phase III data by mid-2015 and an NDA by mid-2016. A follow-on product, Roclatan, adds latanoprost to Rhopressa for four distinct MOA.
Rhopressa inhibits rho kinase inhibitors (RKIs) to increase outflow through the trabecular meshwork, said President and CEO Thomas Mitro. The compound also inhibits norepinephrine transport (NET) to decrease aqueous production and lowers episcleral venous pressure.
Phase II trials showed an IOP-lowering effect similar to that of latanoprost. Mean IOP reductions were - 6.2 mm Hg on day 14 and - 5.7 mm Hg on day 28. A key distinction is that while latanoprost loses about 1 mm Hg in efficacy over 4 weeks, Rhopressa maintains a consistent effect, Mitro added.
The phase III trial program that Aerie hopes will move Rhopressa from candidate to approval is a 90-day, non-inferiority trial versus timolol. Multiple studies will include about 1,300 patients, including at least 100 patients with 12 months of safety data needed for the NDA filing. The trial design also calls for an additional 300 patients with six months safety data needed for an EMA filing.
Aerie’s development program for Roclatan is about 12 months behind Rhopressa. A phase IIb trial that pitted two concentrations of Roclatan against both Rhopressa and latanoprost showed superiority over both components at all time points over 30 days.
The most common adverse event was hyperemia. About 80% of hyperemia was rated as mild by biomicroscopy.
“Roclatan is a very good drug for the reduction of IOP compared to current standards of care,” Mitro said. “We are looking forward to launching phase III trials by the middle of this year.”