DUBLIN – Shares in Nicox SA climbed more than 20 percent Thursday on news that its lead drug candidate, Vesneo (latanoprostene bunod; formerly BOL-303259-X), which is partnered with Bausch + Lomb, hit the primary endpoint in two phase III pivotal trials in glaucoma, paving the way for a new drug application (NDA) during the first half of 2015.

The two double-masked phase III studies, Apollo and Lunar, recruited 840 patients in total, who were randomized to receive either a daily dose of Vesneo, a nitric oxide-donating prostaglandin F2 alpha analogue, or a twice-daily dose of a comparator drug, timolol maleate, a nonselective beta-adrenergic receptor antagonist or beta blocker, which has a long history of use in the indication.

The primary endpoint of each study was the not particularly high hurdle of noninferiority to timolol in terms of reducing intraocular pressure (IOP) – which builds up due to improper draining of aqueous humor from the eye – at specified time points during the three-month study.

"Timolol was one of the early products and is frequently used as a comparator in efficacy studies," Nicox's vice president of corporate development, Gavin Spencer, told BioWorld Today. "This study was designed to be suitable for submission to the FDA."

Patients on Vesneo also achieved a reduction in mean IOP of 7.5 mmHg to 9.1 mmHg from baseline, between weeks two and 12 of the two studies. The two companies have not disclosed the reduction achieved by patients on timolol, but the effect of Vesneo was statistically superior to that of the comparator drug (p < 0.05).

Patients recruited in each study had a mean IOP between 24 mmHg and 36 mmHg in both eyes.

Vesneo has two modes of action, Spencer said. Like other prostaglandin F2a analogues, it lowers IOP by activating PGF2a receptors, which leads to an increase in the outflow of aqueous humor through the uveoscleral pathway, normally a secondary pathway for the removal of the fluid. The NO moiety offers an additional activity. It is thought to enhance conventional drainage of aqueous humor through the trabecular meshwork, by increasing levels of cGMP, which alters the contractility of the resident cells.

Bausch + Lomb in-licensed the program in 2010, when it paid $10 million up front, and it handed over another $10 million when the drug hit the mark in a phase IIb trial. Another $162.5 million in regulatory and sales-related milestones are still on the table. Pfizer Inc., of New York, is in line to receive some of that cash and a fraction of Nicox's royalty stream, having retained a residual interest in the program it originally in-licensed back in 2004 but terminated in 2009. (See BioWorld Asia, Aug. 12, 2009.)

Pfizer had sought a replacement for Xalatan (latanoprost), a prostaglandin F2 alpha analogue that attained sales of $1.75 billion in 2010 before coming off patent in the U.S. during 2011 and Europe in 2012. It exited the collaboration when Vesneo failed to demonstrate what it regarded as sufficient superiority to latanoprost.

Vesneo subsequently outperformed latanoprost in a phase IIb trial, but whether that will be sufficient to persuade payers to choose a new branded drug over a generic is an open question for now. In addition to prostaglandin analogues, beta blockers and carbonic anhydrase inhibitors are also widely used in managing glaucoma.

Also in development is Bedminster, N.J.-based Aerie Pharmaceuticals Inc.'s quadruple-acting combination drug Roclatan, which recently aced a phase IIb trial. Inotek Pharmaceuticals Corp., of Lexington, Mass., is developing an A1 subtype adenosine mimetic called trabodenoson, which protects against the loss of retinal ganglion cells. Ophthalix Inc., of Carson City, Nev., is developing CF101, an orally administered A3 adenosine receptor agonist with anti-inflammatory properties. (See BioWorld Today, June 26, 2014, and Sept. 30, 2013.)

Nicox, of Sophia Antipolis, France, and Bausch + Lomb, a subsidiary of Laval, Quebec-based Valeant Pharmaceuticals International Inc., hope to launch Vesneo in mid-2016, and they forecast peak annual sales in the U.S. of $500 million and global sales of $1 billion.

Nicox recently availed of an option to co-promote the product in the U.S., but the financial implications of that decision are not yet clear. "We need to negotiate the detail of that with Bausch + Lomb," Spencer said.

Plans for Europe and other regions are less advanced. "They are considering the best way forward in territories outside the U.S.," Spencer said.

Shares in Nicox (PARIS:COX) peaked at €2.80 (US$3.57) during trading Thursday, before closing at €2.62, a 21 percent gain. Notwithstanding the buying spree, investors are still cautious on the stock. Nicox is currently valued at just €196 million.