Vertex ‘ends the year in pain’ as latest non-opioid drug data disappoint

Vertex Pharmaceuticals lost more than $15 billion in value Thursday as new data on its closely watched pain drug disappointed Wall Street.

The medication is meant to be a non-addictive alternative to opioids, and has shown in multiple clinical trials the ability to alleviate acute pain as well as a form of chronic nerve pain. Vertex asked the Food and Drug Administration for approval in the acute setting earlier this year. A decision should come before the end of January.

Hoping to show the drug’s versatility, Vertex also sponsored a mid-stage trial focused on painful “lumbosacral radiculopathy,” or LSR, a common condition in which nerves in the lower back become compressed or irritated, leading to sharp bursts of pain there and in the legs. The study was technically successful, according to the newly issued results, but not to the degree analysts wanted.

The main goal was to demonstrate Vertex’s drug significantly decreases pain, as measured by a patient-reported rating scale where a score of 0 indicates no pain and a score of 10 indicates the worst pain possible. There, the drug succeeded. Data from 102 participants showed scores dropped a little more than 2 points on average over a 12-week testing period.

However, the experiment also had a “reference arm” in which participants received a placebo. That arm showed an almost 2-point average reduction in pain scores, suggesting that, at least statistically, the placebo performed no different than Vertex’s drug.

Vertex executives tried to explain the results on a conference call. They said after-the-fact analyses of the data found the placebo group’s responses were better than expected, but also varied substantially across the different trial sites. Pain, like many neurological conditions, is extremely difficult to assess because it’s often subjective. On that 10-point scale, one patient may report a “4” while another reports a “7,” even though they’re experiencing the same type of pain.

Vertex said roughly 40% of sites had a “greater separation” between the two arms. At those sites, the drug-treated group still experienced around a 2-point reduction in pain, while the placebo group didn’t fare as well. To Vertex, that suggests its next studies need to be more innovative to control for oversized placebo responses. The company plans to consult with regulators and then push forward into late-stage testing for painful LSR.

“Sometimes, what you do in Phase 2 and the results you get, teaches you that you need to do something different,” said Reshma Kewalramani, the company’s CEO, during the conference call. “That’s what we’ve learned from this trial.”

Vertex is considering several design elements that might address the placebo response issue. It’s “pretty clear,” according to Kewalramani, the company should enroll a limited number of trial sites and thoroughly instruct researchers about training patients to respond to the pain questionnaires in a consistent way. Kewalramani also brought up a “placebo run-in,” a tactic in which all participants are given a placebo at the onset of the study, and those who have strong responses are then excluded.

Vertex’s share price, which was down 13% by late morning Thursday, suggest investors aren’t sold on the company’s reasoning or plans.

“We continue to be confused by management’s strong defense” of the data, which look “very messy,” wrote Paul Matteis, an analyst at the investment bank Stifel, in a note to clients.

Matteis argues that Vertex’s analysis of those 40% of trial sites “doesn’t do much” to show the drug offers “real clinical benefit.” Additionally, the placebo response isn’t much different than what would’ve been expected based on prior trials in this condition. “Simply put, it’s not obvious that this study failed because of placebo performance,” he wrote.

Matteis and his team still think Vertex’s drug can be a “very significant commercial success” without an approval in LSR. They’re not alone. Evercore ISI estimates annual revenue from the drug could climb to $5 billion in 2035.

Others, though, aren’t so convinced. Baird analyst Brian Skorney wrote in his own note to clients that Vertex’s drug “ends the year in pain.”

“We continue to believe that the reality of [the drug] is significantly different than the lofty expectations attributed to it,” Skorney wrote. “Even considering a pivotal study based on this data strains credulity.”

This post has been syndicated from a third-party source. View the original article here.