VESNEO (latanoprostene bunod)

BOL303259 HDFDA filing expected mid-2015 following positive top-line efficacy results from pivotal phase 3 studies

VESNEO (latanoprostene bunod) is a nitric oxide-donating prostaglandin F2-alpha analog in phase 3 clinical development for the reduction of intraocular pressure (IOP) in patients with glaucoma and ocular hypertension. It was licensed to Bausch + Lomb by Nicox in March 2010.

In September 2014, Bausch + Lomb and Nicox announced positive top-line results from the pivotal phase 3 studies conducted with VESNEO. These studies met their primary endpoint and showed positive results on a number of secondary endpoints.

The pivotal phase 3 program includes two separate randomized, multicenter, double-masked, parallel-group clinical studies, APOLLO and LUNAR, designed to compare the efficacy and safety of VESNEO administered once daily (QD) against timolol maleate 0.5% administered twice daily (BID) in lowering IOP in patients with open-angle glaucoma or ocular hypertension. The primary endpoint of both studies, which include a combined total of 840 patients, was the reduction in mean IOP measured at specified time points during three months of treatment. The collection of patient safety data for a total of up to 12 months is still ongoing. The phase 3 studies are pivotal for U.S. registration and are being conducted in North America and Europe.

The primary endpoint of non-inferiority to timolol maleate 0.5% was achieved in both Phase 3 studies. Additionally, VESNEO showed a reduction in mean IOP of 7.5 to 9.1 mmHg from baseline between 2 and 12 weeks of treatment in the two phase 3 studies. This IOP effect was statistically superior (p < 0.05) to timolol in both studies. VESNEO also showed positive results on a number of secondary endpoints. There were no significant safety findings in either study.

Bausch + Lomb expects to submit a new drug application to the FDA for the approval of VESNEO in mid-2015 and expect to launch it in the US in the first half of 2016, pending FDA approval.

In July 2013, Bausch + Lomb initiated two additional studies in Japan: JUPITER (Phase 3) and KRONUS (Phase 1). A confirmatory efficacy study is expected to be required for the Japanese registration of latanoprostene bunod.

Phase 2b top-line results

A phase 2b study conducted by Bausch + Lomb with latanoprostene bunod met its primary efficacy endpoint and showed positive results on a number of secondary endpoints, including responder rate.
Bausch + Lomb conducted a randomized, investigator-masked phase 2b study to identify the most efficacious and safe dose of latanoprostene bunod for the reduction of IOP. The study enrolled 413 patients across 23 sites in the United States and Europe. Patients were randomized to receive either latanoprostene bunod (various concentrations) or latanoprost 0.005% once a day in the evening for 28 days.
 
The phase 2b study met its primary efficacy endpoint and showed positive results on a number of secondary endpoints. The primary efficacy endpoint was the reduction in mean diurnal IOP on day 28. Latanoprostene bunod consistently lowered IOP in a dose-dependent manner. All four doses tested showed greater IOP reduction compared with latanoprost 0.005%, with the differences for two of the four does reaching more than 1mmHg (statistical significance: p<0.01).
 
The most efficacious dose of latanoprostene bunod also showed positive results on a number of secondary endpoints, including consistently better control of IOP over 24 hours on day 28 as well as a statistically significant greater percentage of responders vs. latanoprost 0.005%, defined as patients achieving an IOP of 18mmHg or less. The responder rate was 68.7% for the most efficacious dose of latanoprostene bunod, compared to 47.5% for latanoprost 0.005% (p=0.006).
 
The safety of latanoprostene bunod was comparable to latanoprost. The most common adverse event was ocular hyperemia (red eye), which occurred at a similar rate across all treatment groups.