Nicox SA reported new phase 3 data, published in the American Journal of Ophthalmology, from the Mont Blanc pivotal trial evaluating NCX 470 for the treatment of patients with open-angle glaucoma (OAG) or ocular hypertension (OHT).
Let’s start with NCX 470.
As Nicox’s lead investigational candidate, NCX 470 is a novel nitric oxide (NO)-donating bimatoprost formulation that features intraocular pressure (IOP)-lowering effects of NO and prostaglandin analogs (PGAs).
Note: NO possesses small, naturally-occurring signaling properties that play a critical role in IOP regulation via the activation of soluble guanylate cyclase (sGC).
Talk more about NO.
NO is known to provide “additional IOP-lowering efficacy by enhancing aqueous humor drainage from the eye via a different mechanism of action [MOA] to that of PGAs,” according to Nicox.
And in regards to NCX 470: This NO-donating, PAG bimatoprost combination contains a dual mechanism of action that, according to the company, has been clinically proven to achieve superior IOP-lowering.
Now a refresher on Mont Blanc.
Mont Blanc (NCT04445519) is a prospective, randomized, adaptive dose-selection, double-masked, parallel-group phase 3 trial that enrolled 691 patients (and analyzed 661) with OAG or OHT.
Patients were initially randomized to receive either:
- NCX 470 0.1%
- NCX 470 0.065%
- Latanoprost 0.005%
How was the final NCX-470 dose identified?
By performing an interim analysis after at least 30 participants had completed their Week 2 clinic visit; then, the participants were randomized (again) to the final NCX 470 dose (0.1%) (n = 328) or latanoprost (n = 333) for 12 weeks.
Any previous findings on it?
As reported in October 2022, the study achieved its primary objective of demonstrating non-inferiority to latanoprost, with NCX 470 exhibiting an IOP lowering of 8.0 to 9.7 mmHg from baseline (vs 7.1 to 9.4 mmHg for latanoprost).
Side note: A second phase 3 trial—Denali (NCT04630808)—is ongoing in both the United States and China, with topline data slated for 2025.
Also of note: both studies were approved to support a potential new drug application (NDA) submission for NCX 470.
Are there other ongoing studies?
Just one: the first patient was recently enrolled in the phase 3b Whistler study (NCT05938699).
The target: to investigate NCX 470’s MOA on aqueous humor parameters, including the trabecular meshwork (TM) outflow and episcleral venous pressure (EVP).
I’m up to date! Now talk about these latest results…
The investigators reported that, for the NCX 470 group at baseline, the mean (SD) IOP was 28.3 (2.0) mmHg at 8 a.m. and 25.5 (2.5) mmHg at 4 p.m.
Also: IOP was significantly reduced at all on-treatment timepoints (ranging from 8.0-9.7 mmHg ( p<0.0001)
And for the latanoprost group?
A significant reduction of mean baseline IOP was noted as well, with 28.2 (2.0) mmHg at 8 a.m. and 25.4 (2.4) mmHg at 4 p.m.
As with the NCX 470, this reduction was noted at all on-treatment time points (ranging from 7.1-9.4 mmHg (p<0.0001).
Did the NCX 470 group surpass latanoprost for IOP reductions?
Indeed they did. This was the case at the 3-month visit for all six time points—further, the reductions were significantly greater (p<.05) at four of the six time points, the study authors reported.
Note: The primary outcome measure of non-inferiority of latanoprost was also demonstrated at all six time points.
Any adverse events?
Out of all participants, a total of 14 (eight from the NCX 470 group and six from the latanoprost group) discontinued due to adverse events (AEs).
The most common: conjunctival/ocular hyperemia; more common among NCX 470-treated patients vs latanoprost.
Lastly … expert opinion?
The study authors concluded that NCX 470 was well-tolerated and surpassed latanoprost in lowering IOP at all time points.
With a dual mechanism of action that enhances both uveoscleral and trabecular outflow,“ they wrote, “NCX 470 could become an important first-line therapy for IOP reduction in glaucoma.”