Vertex discontinues development of its Nav1.8 pain drug VX-961.
Deep within the Full-Year and Fourth-Quarter 2019 Financial Results for Vertex you can find this statement:
“Pain: The company announced today that it has discontinued Phase 1 development of VX-961. The company continues to advance a portfolio of NaV1.8 inhibitors into the clinic. As part of this strategy, Vertex plans to advance an additional molecule into clinical development in the first half of 2020.”
This is disappointing news as Vertex are one of only a few pharma companies actively investing in pain R&D.
They have gone “all in” on the Nav1.8 mechanism following three positive PoC’s from its lead compound VX-150.
“Vertex now has positive Phase 2 data for VX-150 in multiple pain conditions, including chronic pain caused by osteoarthritis and small fiber neuropathy, as well as acute pain following bunionectomy surgery. The company continues to invest in the discovery and development of other potential pain molecules that target NaV1.8 and other new pain mechanisms and anticipates initiating clinical development with the first of these molecules in 2019.”
However, sodium channels are difficult compounds to develop. Many companies have tried over the last 2 decades but failure to find a safety margin between efficacy and side effects has stopped many compounds as has poor drug characteristics such as PK.
Where to go from here:
Although it is interesting that VX-150 seems to demonstrate a broad analgesic profile clearly it is not suitable for full development as back-up compounds are being prioritised.
Despite there being over 100 diseases associated with pain Vertex have looked at the typically used pain conditions of acute pain, OA and neuropathic pain.
If Vertex are lucky to find a compound that has the right PK and safety characteristics, I think there is still some work to do to find the right clinical development path.
The broad potential efficacy is interesting but could ultimately prove a downfall.
The broad analgesic develop was a key aim a decade ago but the multiple trials required for a broad label are exhaustive creating extortionate development costs in the $100’s and $100’s of millions.
Time take to reflect back on the Nav1.8 target and find the strongest link to one of the >100 pain conditions would be well spent. Creating more of a focused clinical development and working with patients to identify and develop PROs for the most relevant endpoints could be a key success factor.