Cara touts subgroup in failed atopic dermatitis trial, but stock craters
Cara Therapeutics will join the growing list of biotech to launch a Phase III despite failing Phase II.
The itch-focused company announced Thursday that its central drug, a pill called Korsuva, failed to significantly alleviate itching in patients with atopic dermatitis when compared with placebo. The drug missed both the primary endpoint, the change in average score on a standard itch scale after 12 weeks, and the key secondary endpoint: The proportion of patients who improved by at least 4 points.
On the primary endpoint, the study neared statistical significance, with a p-value of 0.073 for the high dose and 0.111 for all dose. But it did not for the secondary endpoint, with p-value of 0.55 and 0.59 for the mid and high doses.
The trial is one of several Cara is running for the drug across a variety of diseases. The FDA is now evaluating under priority review an injectable form of Korsuva for dialysis, a potentially lucrative indication that Vifor spent $150 million upfront to commercialize in the US. Atopic dermatitis is one of two other mid-stage efforts Cara is running for Korsuva after their pain program tanked, despite their best efforts to spin the data.
Although they missed the two key endpoints, Cara is arguing that their results in a sub-group offer a path to a pivotal trial and eventual approval. In what the company refers to in their press release as another “Primary Endpoint,” the drug significantly improved symptoms in a subgroup of patients who had a more mild form of atopic dermatitis. This group, representing 257 patients, or 64% of the 401-person study, saw statistically significant improvements in itching symptoms after 12 weeks, with a p-value of 0.036.
Patients in the milder group were also more likely to see an improvement by at least 4 points, with a p-value of 0.03. In that group, 32% of patients in the treatment group saw a 4-point improvement compared to 19% of placebo patients.
“We view this as a positive outcome,” Cara CMO Joana Goncalves said on a conference call “What we learned in the study is that [Korsuva] is most effective in the mild to moderate patient population.”
Cara now plans to move forward with a Phase III for just the mild to moderate patient population. Investors, however, appeared unconvinced by the drug’s prospects, with the stock $CARA dropping 40%, from $25.67 t0 $15.67.
On Cara’s conference call, analysts raised questions about whether the effect size they saw in the subgroup would be meaningful for patients and whether they’d be able to charge as much as they would have for more severe patients. They also pointed out that, on one endpoint, patients who received a low dose performed better than patients on the high dose — the opposite of what drug developers generally look for.
“Does that make sense to you?” Stifel’s Annabel Samimy asked.
CEO Derek Chalmers said it was just an anomaly. The individual dose groups were simply not large enough.
“We think that’s simply a powering issue,” said Chalmers.
The company also argued that mild to moderate patients still present a significant opportunity, as they can’t take injectable drugs like JAK inhibitors and they aren’t sufficiently covered by over-the-counter options.