VX-993

Vertex Pharmaceuticals’ bid to expand into non-opioid pain treatments was dealt a heavy blow as its next-generation drug VX-993 failed a critical mid-stage trial, triggering a sharp 14.4% after-hours share drop. The drug reduced pain by 74.5 points versus 50.2 for placebo over 48 hours in bunionectomy patients, but the difference did not reach statistical significance. As a result, Vertex will stop developing VX-993 as a standalone therapy and has also decided not to advance a planned study of its approved pain drug Journavx for lower back and leg nerve pain, following discussions with the FDA. The company will instead focus on seeking approvals for Journavx in diabetic nerve pain and other types of nerve pain. Despite the setback, VX-993 was found generally safe, with mostly mild to moderate side effects and no serious safety signals. Analysts and investors, who had high hopes for Vertex’s diversification beyond cystic fibrosis drugs, called the updates “disappointing” even as Q2 results beat expectations. Vertex’s pain portfolio faces new uncertainty, clouding its strategy to capture a lucrative non-opioid market and putting further pressure on its share price.

Journavx scored a historic FDA nod as an non-opioid treatment option for acute pain in late January. After the FDA's landmark approval of the opioid-free acute pain reliever Journavx in January, Vertex Pharmaceuticals has hit a snag on its path to expand the potential blockbuster’s reach into multiple forms of chronic pain.Vertex is pursuing a broad label for Journavx (suzetrigine) in peripheral neuropathy (PNP), a chronic pain condition that occurs when the nerves outside the brain and spinal cord become damaged. Vertex has been running clinical trials on Journavx in two subsets of the condition, lumbosacral radiculopathy (LSR) and diabetic peripheral neuropathy (DPN), in hopes of racking up a broad PNP nod in one go.But the FDA has other ideas, Vertex CEO Reshma Kewalramani, M.D., said on an analyst call Monday.Despite “productive” talks with the regulator on Vertex’s PNP program, “at this time, the FDA does not see a path to a broad indication,” Kewalramani said.In turn, Vertex is waylaying plans to kick off a phase 3 trial of Journavx in LSR and will instead start a second phase 3 study of the pain med in DPN, with the goal to prioritize that specific indication in its PNP approval bid, the CEO explained.Journavx boasts a breakthrough therapy tag from the FDA in DPN, Kewalramani noted on the call. Roughly 2.4 million people suffer from the condition in the U.S., according to a Vertex investor presentation from earlier this year.As for the path toward further PNP nods, Vertex’s plan is now to go “DPN first, then add on single indications, but work with the [FDA] to get to broad PNP,” Kewalramani said.While the FDA doesn’t currently “see a path to PNP” for Journavx, “we have a clear agreement on DPN,” Kewalramani added.  As for the development trajectory of Vertex’s pain portfolio overall—and whether the company could eventually pursue broader forms of chronic pain such as joint pain—Kewalramani told analysts that “we’re still very focused, first and foremost, on acute and then neuropathic [pain]. We will get to the musculoskeletal, but I don’t see that in the highest priorities.”Journavx scored a historic FDA nod as an non-opioid treatment option for acute pain in late January. Vertex has positioned the medication as a potential solution to the crisis of addiction and overdoses that has accompanied the widespread use of narcotic painkillers in the U.S.The drug, taken orally, is a voltage-gated sodium channel (NaV) inhibitor that prevents pain sensations from reaching the brain by targeting a signaling pathway in the peripheral nervous system.With the green light in acute pain locked in, Vertex was hoping the FDA would approve the drug in a broad PNP setting—representing a pool of roughly 11 million U.S. patients—through positive trial results in LSR and DNP, which make up about 60% of PNP cases, the company’s chief operating officer, Stuart Arbuckle, said last year. The Journavx news comes as Vertex on Monday revealed another hitch in its pain portfolio expansion efforts.In a midstage study, the sodium channel inhibitor VX-993—intended as a follow-up to Journavx—failed to beat placebo at improving pain scores in patients who’d undergone bunion removal surgery. The asset failed to top scores from the trial’s control arm at three different doses, and, as a result, Vertex is shelving development of VX-993 as a monotherapy for acute pain.Vertex’s stock took a nosedive after it unveiled second-quarter earnings and the pain pipeline updates after market close Monday. As of midmorning Tuesday, the stock was trading down more than 15%.