Cara, with its 2nd phase 3 in the bag, eyes 2020 filing for itch drug

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Unlike traditional opioids, which work by activating the mu opioid receptor in the central nervous system, Korsuva has a different target: the kappa opioid receptor in the peripheral nervous system. (Pixabay)

Patients with chronic kidney disease (CKD) may take medicines for blood pressure and other related conditions, undergo regular dialysis treatments or even require a transplant. But what their care often neglects is pruritis—the stubborn, systemic itch that plagues as many as 40% of dialysis patients. With positive phase 3 data, Cara Therapeutics is one step closer to changing that.

The company’s treatment, called Korsuva, beat placebo at relieving itch in a study of 473 dialysis patients with moderate to severe pruritus linked to CKD. The results come from the second of two pivotal phase 3 studies that will support an FDA submission in the second half of 2020. A European filing will follow “shortly thereafter,” Cara CEO Derek Chalmers, Ph.D., said in a statement.

The study hit its primary endpoint, with more than half of the patients taking Korsuva logging a three-point improvement from baseline on a measure of their most severe itch—54% compared to 42% of patients on placebo. Patients in the Korsuva group also recorded a boost in quality-of-life measures over patients in the placebo group.

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Korsuva (difelikefalin) is an opioid agonist, like morphine and other opioid painkillers. But unlike morphine and its peers, which work by activating the mu opioid receptor in the central nervous system, Korsuva has a different target: the kappa opioid receptor in the peripheral nervous system. The hope is that by avoiding receptors in the brain and spinal cord, the drug will sidestep side effects like nausea, respiratory depression and abuse potential.

RELATED: Cara signs $540M deal with Fresenius and Vifor Pharma to commercialize Korsuva

“The reason we want to treat it is it’s highly prevalent,” Chalmers told FierceBiotech. “That level of constant, systemic pruritis severely affects quality of life for hemodialysis patients … There is a correlation between pruritus severity and increased mortality in hemodialysis patients who already have very serious chronic kidney disease.”

Constantly scratching their skin makes these patients more susceptible not just to local infections on the surface of the skin but also to systemic infections, which can land them in the hospital.

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Cara is developing Korsuva as an injection that can be given to patients in a clinic after they have undergone a dialysis session.

“In the U.S., that’s three times per week, so patients don’t have to think about taking another medication on a daily basis,” Chalmers said. A person with healthy kidneys would normally filter out a drug like Korsuva, but Cara’s target patient group has impaired kidney function, which keeps the drug in their system for days at a time for a better effect on their pruritus, he said.

Cara is also working on an oral form of Korsuva. Although the pill failed to beat placebo in a phase 2b study in osteoarthritis pain in 2017, the company is testing it in other types of pruritus. In December, it posted encouraging results from a phase 2 study in moderate to severe CKD and expects top-line data from phase 2 studies testing the pill in atopic dermatitis and primary biliary cholangitis by the end of the year.

“If we can show a significant benefit across these patient populations, we would see the oral tablet having a broad label for pruritus across medical conditions,” Chalmers said.

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