Vertex weakens after neuropathic pain trial reads out

Vertex Pharma's non-opioid painkiller suzetrigine was unable to perform better than placebo in a phase 2 trial in lumbar radiculopathy (LSR), a form of neuropathic back pain, ahead of an FDA decision on two acute pain uses.

The company emphasised that the NaV1.8 inhibitor met the primary endpoint with a statistically significant and "clinically meaningful" 2.02-point reduction from baseline in the Numeric Pain Rating Scale (NPRS) used to measure leg pain intensity in painful LSR, also known as sciatica.

However, the placebo group also saw a 1.98-point in the NPRS and – despite Vertex's assertions that the study was not powered to show a difference between the drug and placebo – shares fell by more than 12% as investors reacted to the data.

The fall seemingly was sparked by concerns that suzetrigine may not be as effective in chronic, neuropathic pain indications, a much larger market opportunity than acute pain relief. The NaV1.8 inhibitor has been held up as a potentially major step forward in the bid to find effective pain relief free of the side effects and risk of dependency that accompanies the use of opioids.

Carmen Bozic, Vertex's chief medical officer, said one explanation for the results could be the high placebo response in this study, which also revealed a lot of variability between study sites.

Vertex said it intends to move suzetrigine into phase 3 in painful LSR "pending discussions with regulators." Changes to trial design may be able to "better control the placebo response and separate the treatment effect of suzetrigine from placebo in future studies," it added.

"Today's LSR results are consistent with previous studies of this pain signal inhibitor in terms of showing a meaningful treatment effect across pain conditions and a favourable safety profile," she added.

"We remain committed to studying LSR and innovating our phase 3 study design to control for the placebo effect as we advance suzetrigine into pivotal development for this condition."

Suzetrigine is already under regulatory review at the FDA for the relief of moderate-to-severe acute pain in patients undergoing abdominoplasty and bunionectomy surgery, with a decision due by 30th January after a priority review.

Along with LSR, Vertex is also running a trial of suzetrigine in painful diabetic peripheral neuropathy (DPN), another form of chronic, neuropathic pain.

Commenting on the LSR data, principal investigator Christine Sang of Brigham and Women's Hospital, said that the data showed "clearly…reduced pain intensity" with suzetrigine, noting that LSR pain is a heterogeneous condition that is notoriously difficult to treat and "managing the placebo response in pain trials is a complex challenge."

Some analysts have suggested that if approved for acute and neuropathic pain indications, suzetrigine could become a multibillion-dollar blockbuster.

Image by Mohamed Hassan from Pixabay