Vertex drops VX-961 to continue search for perfect pain drug

Reshma Kewalramani, chief medical officer at Vertex (Vertex)

Vertex has stopped development of VX-961 after getting a look at phase 1 data. The NaV1.8 inhibitor failed to meet Vertex’s desired pharmacokinetic and tolerability profile, leading it to dump the drug and outline plans to move a follow-up candidate into the clinic. 

VX-961 moved into early-phase development last year on the back of midphase data linking VX-150, another NaV1.8 inhibitor, to improved outcomes in people with acute, chronic and neuropathic pain. The midphase data led Vertex to conclude NaV1.8 inhibition can yield opioid-like efficacy without the side effects or abuse potential associated with that class of medicines. 

Yet, Vertex opted to hold off on starting a late-phase trial of VX-150, choosing instead to gather data on the drug’s siblings before deciding which molecule to advance. The early phase study of VX-961 was part of Vertex’s effort to triage its NaV1.8 inhibitors.

VX-961 fell at the first hurdle. On Vertex’s fourth-quarter results conference call with investors, Reshma Kewalramani, the company’s chief medical officer, said the phase 1 showed VX-961 lacked the desired pharmacokinetic and tolerability profile. 

Vertex’s willingness to drop VX-961 based on those variables reflects a belief that safety and efficacy are “table stakes” in pain. To succeed, Vertex is looking for “a molecule with the perfect PK” for the indication, Kewalramani said. That search is underpinned by an understanding of how pain drugs are used. Once or twice daily dosing is one essential requirement but is far from the only factor. 

“We need to ensure that this medicine can be taken with food or without food. If you’re talking about acute pain, immediately post-surgery, being able to take it without food is going to be really important. We’re also thinking about [drug-drug interactions] and [cost of goods sold],” Kewalramani said.

Vertex’s criteria for the ideal molecule differ somewhat across acute, chronic and neuropathic pain, which Kewalramani sees as “three distinct groups.” The search for the chemistry that will meet the criteria goes on, but Vertex is sure NaV1.8 inhibition is the right approach. 

“We’ve cracked the biology,” Kewalramani said.

Vertex will open a new stage of its search for the perfect NaV1.8 inhibitor when it moves another of VX-150’s siblings into phase 1 later in the first half of 2020. Data from that trial will inform Vertex’s decision about which pain drug to advance into later-stage development. 

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