Cara tanks after oral pain drug misses mark in phase 2b

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Shares in Cara fell on the CR845 pain data. (bfishadow [CC BY 2.0])

A phase 2b trial of Cara Therapeutics’ CR845 has missed its primary endpoint. An oral formulation of the kappa opioid receptor agonist failed to outperform placebo on a pain score, wiping 28% off Cara’s stock in after-hours trading.
Investigators enrolled 476 people with osteoarthritis of the hip or knee in the trial and randomized them to receive one of three doses of CR845 or placebo. Participants took the tablets twice a day for 8 weeks. Cara gauged the effectiveness of CR845 by tracking subjects’ pain intensity scores and comparing them with a baseline.
CR845 failed to move the needle against this primary endpoint. Patients who took the highest dose of CR845 experienced a 35% reduction in mean joint pain score as compared with placebo. This fell short of statistical significance. The p-value was 0.111.
Cara tried to bury that negative result under more upbeat but less important findings. Results cherry-picked by Cara to lead the press release included the performance of the highest dose in patients with hip pain. The trial linked CR845 to a statistically significant improvement in pain scores within this subgroup of patients. However, without a rationale for why CR845 would treat pain in the hip but not the knee, the importance of this finding is questionable. 
Investors were less inclined to focus on the perceived positives. Shares in Cara slipped 28% once the data broke after hours. That decline, while severe, only partly wiped out gains Cara made in the back end of June on the strength of a breakthrough designation and data monitoring decision.
Both of those pieces of news related to the intravenous formulation of CR845. That formulation is in a phase 3 trial as a treatment for postoperative pain, the continuation of which was supported by an independent committee after an interim review. Cara is also developing the IV formulation as a treatment for pruritus in patients with chronic kidney disease who are undergoing hemodialysis. That is the indication in which the drug now has breakthrough status.
Those indications provide Cara with opportunities to bounce back from the phase 2b data. Cara is yet to give up on the oral formulation, as well. 
“The drug was observed to be well tolerated over the treatment period and this overall data set will inform both our dose selection and patient population in designing our next trial of oral CR845 in OA patients,” Cara CMO Joseph Stauffer said in a statement.