In after-hours trade on August 4, 2025, Vertex announced results from its ongoing phase 2 randomized study using its follow-up sodium channel inhibitor of NaV1.8, VX-993, to treat patients with acute pain after bunionectomy surgery. The hope was that this next-gen therapy could achieve data superior to that of the company’s existing pain therapy pipeline. By that, I mean it had already received FDA approval of JOURNAVX (suzetrigine) for the treatment of adults with moderate-to-severe acute pain. This U.S. marketing approval was ideal because it made history in being the first new class of pain medicine approved in a 20-year period. This was not just a monumental approval because the company received the right to generate revenue from it; it was because it could offer a new non-opioid pain treatment alternative.
The downside is that while this offers the ability to target short-term pain for many patients, Vertex did not gain favor with the FDA to expand the label to include a broad Peripheral Neuropathic Pain (PNP) label on the basis of its update. More about this below, but the point is that the failure of VX-993 is a huge blow to the company. The reason why is because the plan was to see if this other follow-on candidate could be able to help treat patients in the ongoing phase 2 randomized study treating acute pain in patients after bunionectomy surgery. This type of surgery involves the removal of a bunion at the joint where the big toe meets the foot. After said surgery, patients experience pain for an extended period of time, for about 6 weeks or more.
Typically, an opioid would be given for these patients, but as is known now, this type of drug has an addiction to it. The hope was that VX-993 could be offered as an alternative to the pill form and be given to patients via intravenous (IV) infusion instead. On top of the potential to use higher dosing to see if further efficacy could be obtained with it. Unfortunately, this phase 2 study failed to help these patients with acute pain after bunionectomy surgery. There were two evaluations being done on whether or not this drug would pass muster to be evaluated in newer studies. The first goal was to see if it could at least perform better than a placebo on the primary endpoint, and this was a failure.
The primary endpoint was looking at the sum of the pain-intensity difference over a 48-hour period (SPID48). A total of 367 patients were randomized to one of three doses of VX-993 (high-dose, mid-dose, or low-dose) or placebo over such a 48-hour period. The final outcome was that a placebo fared quite decently, achieving an SPID48 score improvement of 50.2, while those taking the highest dose (best value) achieved an improvement of 74.5 points. There is no doubt that the high dose of this drug performed better than the placebo, but the problem is that such a difference was not statistically significant, with a p-value of 0.1190. Besides seeing a bit of this follow-on NaV1.8 inhibitor over placebo, it was to see an improvement over the other approved drug in Vertex’s pipeline, which is JOURNAVX.
With the failure of this phase 2 randomized study, along with other unimpressive data collected to date, it made the decision to not move forward using VX-993 as a monotherapy in late-stage testing for acute pain. I commend Vertex for advancing a non-opioid treatment option. The beauty of JOURNAVX is its ability to act as a selective NaV1.8 inhibitor. What this means is the ability for it to block these NaV1.8 sodium channels in the periphery so that no pain signals are sent from the periphery to the spinal cord and brain. Thus, opioids work in an opposite function, which is to block pain perception directly inside of the brain. This is the reason why this FDA-approved drug does not have the addiction that is associated with opioids.
All is not lost though, because this one failure may lead to the company not specifically advancing VX-993, but that doesn’t mean it doesn’t have a path forward with JOURNAVX. Believe it or not, it still has a sufficient pathway forward with this drug, and thus this is good news for Vertex. Specifically, this one failure with VX-993 will not define its pain treatment pipeline going forward. For example, it is still moving ahead testing the use of JOURNAVX in a phase 3 study targeting patients with diabetic peripheral neuropathy (DPN). This specific disorder entails patients who have diabetes that causes damage to the nerves, leading to severe pain.
As I stated above, an end-of-phase 2 (EOP2) meeting that happened did not come with a welcomed outcome. The FDA indicated that it was not inclined to allow the company to offer a broad targeting label of Peripheral Neuropathic Pain (PNP). On the flip side, this is just something the FDA doesn’t want for the time being. The company can start off in advancing its late-stage programs of DPN, and if it sees success with these studies, then maybe it could eventually convince the FDA to allow it to move to a broader label for JOURNAVX. If anything, I would say that this big pharma has a lot of time on its hands, and this is because of its dominance in the cystic fibrosis (CF) space. Its therapies pretty much dominate this market, and that was the main reason why it was able to release Q2 2025 financials showing that its revenues increased by 12% to $2.96 billion.
Unfortunately, the phase 2 randomized trial failure of VX-993 targeting patients with acute pain after a bunionectomy surgery stole the show from this impressive revenue increase year-over-year, causing the stock price to plunge in after-hours trading anyways. For what it’s worth, it still has a working pipeline in progress, and positive data from several such programs could be of value to shareholders. Besides the development of JOURNAVX for DPN, other candidates in its pipeline include zimislecel for the treatment of patients with type 1 diabetes (T1D), povetacicept for the treatment of patients with IgA nephropathy (IgAN), and inaxaplin for the treatment of patients with APOL1-mediated kidney disease (rare genetic kidney disease).