Vertex unlikely to repeat their CF success in Pain as they lack a personalized analgesics® approach.

Vertex are looking to other therapeutic areas to repeat their undoubted success in Cystic Fibrosis and create a sustainable pipeline.

Pain has been a key area for them and they have gone “all in” on the Nav1.8 mechanism. Back in 2018 there was unparalleled success following three positive clinical 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.”

https://investors.vrtx.com/news-releases/news-release-details/vertex-announces-positive-phase-2-data-third-proof-concept-study

However, since then there have been disappointments.

Vertex discontinues development of its Nav1.8 pain drug VX-961. https://www.fiercebiotech.com/biotech/vertex-drops-vx-961-to-continue-search-for-perfect-pain-drug

And long silences on the pain front.

However, just last week there was at least some updated from the Vertex Pharmaceuticals CEO Reshma Kewalramani at the Cowen 41st Annual Health Care Conference. Excerpt below:

Phil Nadeau

In the pain field, Vertex has been developing for several years now for 1.8 inhibitors. What's the status of that program? What characteristics do you need to see to advance of a candidate in clinical development? And how likely is that?

Reshma Kewalramani

Yes. So I really appreciate the question because we don't get to talk about pain very often. So I appreciate the question. All right. So pain is a field where we just really haven't had, honestly, any significant innovation in decades. So I'm very enthusiastic about the NAV1.8 target. And I'm excited about it because we have demonstrated that with NAV1.8 inhibitors, that was the VX-150 program, you can interdict on pain, and we had positive results across three studies: acute pain using a bunionectomy model; neuropathic pain as well; as in osteoarthritis, call it a musculoskeletal pain.

Now what we are looking to do is to find a molecule or molecules with, let's just call it, the perfect profile. What I mean by that is formulation, drug-drug interactions, ability to take it with food and without food, manufacturability. That's really the kind of drug-like properties that we're looking at. And there is a molecule that's coming through Phase I that looks pretty good. And I'm optimistic and I'm looking forward to being able to tell you more about that, and that might be able to go to Phase II this year.

https://seekingalpha.com/article/4410843-vertex-pharmaceuticals-incorporated-vrtx-ceo-reshma-kewalramani-presents-cowen-41st-annual

Since the overwhelming success of VX-150 this update is pretty underwhelming as it looks like they struggle to find a druggable asset.

This is disappointing news as Vertex are one of only a few pharma companies actively investing in pain R&D and patients desperately need novel treatments.

The larger problem and potential solution

Vertex have moved away from their focused disease led R&D strategy for Cystic Fibrosis with their efforts in pain. They have gone "all in" for one target but are taking a broad approach to the patient populations.

Despite there being over 100 diseases associated with pain Vertex have looked at the over-used pain conditions of acute pain, OA and neuropathic pain.

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 of $100’s and $100’s of millions.

A real key to success would be to reflect back on the Nav1.8 target and find the strongest link to one of the >100 pain conditions. Taking a more personalized analgesics® approach and creating a focused and efficient clinical development plan would significanlty enhace chances of success. Following their previous approaches in CF and working with patients to identify and develop PROs for the most relevant endpoints would also be a key success factor.