Nicox plans filings for glaucoma after phase 3 win

Nicox is on track to file for approval of its NCX 470 therapy for eyesight-robbing disease glaucoma after it showed efficacy in a second pivotal trial.

The positive data from the Phase 3 Denali trial showed that NCX 470, a nitric oxide-donating bimatoprost eyedrop formulation, was as effective as latanoprost 0.005%, the standard therapy, in lowering intraocular pressure (IOP) in patients with open-angle glaucoma.

That matches the outcome of the earlier Mont Blanc phase 3 trial, which was reported in 2022, although at the time there was some disappointment that Nicox's drug was unable to show superiority to the go-to therapy. Regardless, with two positive trials in hand, Nicox now plans to file NCX 470 for approval in the US and China.

Glaucoma is an eye condition which is usually caused by a build-up of pressure in the eye. It begins when the fluid in the eye cannot drain properly, resulting in IOP increases that can damage the optic nerve, as well as the nerve fibres from the retina, leading to progressive loss of vision and, in some cases, blindness.

In Denali, the IOP-lowering effect from baseline for NCX 470 was 7.9 to 10.0 mmHg, compared to 7.1 to 9.8 mmHg for latanoprost, fulfilling its primary objective.

The 696-subject trial also included a pre-specified secondary efficacy analysis of time-matched change from baseline IOP, with reductions that were numerically greater with NCX 470 than latanoprost at five of six timepoints – at 8 am and 4 pm on weeks two, six, and 12 – with three comparisons reaching statistical significance. However, overall statistical superiority on this secondary measure was not achieved.

On the tolerability front, Nicox said that NCX 470 was not associated with any serious adverse events, and the main side effect was redness in the eye due to dilated blood vessels (conjunctival hyperaemia). All told, 10.1% of patients on NCX 470 discontinued compared to 6.6% in the latanoprost group over up to 12 months of follow-up.

Despite the mixed efficacy results, shares in Nicox had gained almost 10% at the time of writing, suggesting that investors were optimistic of a positive outcome for the planned marketing applications.

France-based Nicox has previously said that NCX 470 addresses a global glaucoma market estimated to be worth around $6 billion a year, and has modelled peak sales of more than $300 million.

The company has commercial partnerships in place with Ocumension for NCX 470 in China, Hong Kong, Macau and Taiwan, as well as Korea and Southeast Asia, while Kowa has rights in the rest of the world, including the US. Phase 3 trials in Japan are underway, while a Nicox spokesperson said discussions with the EMA on the appropriate regulatory route to approval are needed, which will now be the responsibility of Kowa.

"We are now moving forward towards potential recurrent NCX 470 royalty revenue from 2027 onwards," commented Nicox's chief executive Gavin Spencer.

"Our established partnerships with Kowa and Ocumension enable us to accelerate [filing] preparations, whilst also allowing us to focus on potential future strategies for the company," he added.

Nicox is due for a €5 million milestone payment from Kowa on the back of the Denali readout. The company also has a follow-up NO-donating glaucoma candidate (NCX 1728) in preclinical development which has been licensed to Glaukos.

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