Elexacaftor

As Vertex Pharmaceuticals works to get its pain pipeline — key for its growth aspirations — off the ground, the company was hit with a one-two punch of bad news for its programmes on Monday, sending its shares down as much as 15% during after-hours trading. With an acute pain approval already in-hand for Journavx (suzetrigine), Vertex has been exploring a potential expansion for the non-opioid drug into chronic pain, while also advancing next-generation voltage-gated sodium channel inhibitors.Investors already had concerns about whether Journavx could succeed in chronic pain after the company reported in December that the NaV1.8 inhibitor showed no significant benefit over placebo in a Phase II study in patients with painful lumbosacral radiculopathy (LSR). Also known as sciatica, LSR falls into the broad peripheral neuropathic pain (PNP) bucket (see – Spotlight On: Sciatica setback magnifies doubts about Vertex’s suzetrigine in chronic pain). Vertex CEO Reshma Kewalramani confirmed during an investor call Monday that, following an end-of-Phase II meeting with the FDA, the company will not be conducting another trial of Journavx in LSR — and a general PNP approval is, for now, off the table. "While a broad PNP label remains our goal at this time, the FDA does not see a path to a broad indication," she said. "Instead, in light of the discussions and clear agreement with the FDA regarding approval requirements for diabetic peripheral neuropathy, or DPN, we will begin a second DPN Phase III study shortly in order to secure DPN as our first PNP indication for suzetrigine." Last year, Journavx won breakthrough therapy designation from the FDA for DPN, and Vertex launched a Phase III study for the indication. Now with a second late-stage DPN study planned, the biotech expects to finish enrollment for both trials by the end of 2026. "We look forward to working with the agency to secure DPN as our first PNP indication, to expand the indication over time, and to continue to discuss a potential pathway to a broad PNP label," Kewalramani added. Next-gen NaVsVertex also revealed that a next-gen, intravenously delivered NaV1.8 inhibitor, VX-993, failed a Phase II study in patients experiencing acute pain after bunionectomy surgery. The candidate did not lead to statistically significant pain relief versus placebo, and as a result, the drugmaker is halting development as a monotherapy to treat acute pain.  However, the company will continue a Phase II study of VX-993 in patients with DPN "to further define the exposure response relationship and maximal efficacy of NaV1.8 inhibitors in this chronic pain indication," Kewalramani said. According to ClinicalTrials.gov, the study is expected to finish in mid-2026. She also provided a brief update on Vertex's preclinical NaV1.7 inhibitors, saying that the company is "very encouraged" by the pain candidates' progress, and that it plans to advance programmes alone or in combination with NaV1.8 inhibitors.Revenue beatVertex also shared its second-quarter financials on Monday, and while positive, the results weren't enough to offset investor disappointment with its pain portfolio. The drugmaker brought in $2.96 billion in total revenues for the quarter, up 12% year-over-year and ahead of consensus estimates of about $2.9 billion. The bulk of its revenues came from its cystic fibrosis drug elexacaftor/tezacaftor/ivacaftor and ivacaftor, which is sold as Trikafta in the US and Kaftrio in Europe. The product raked in $2.55 billion in sales.Meanwhile, the second quarter was the first full three-month period on the market for Journavx, which had $12 million in sales.Vertex reiterated its full-year guidance on Monday, predicting revenues to fall between $11.85 billion and $12 billion for 2025.