Therapeutic Focus

Chronic Liver Disease associated Pruritus (CLD-aP)

Pruritus is a Significant Problem for Patients who Suffer from CLD

Millions of Americans suffer from chronic liver diseases (CLD) of various etiologies ranging from hepatitis to cirrhosis to primary biliary cholangitis (PBC). Pruritus is a common and irritating symptom in patients who suffer from CLD, especially those with chronic cholestatic disease. Severe pruritus can have debilitating effects and can lead to a significant reduction in a patient’s quality of life. According to a study conducted by IQVIA, nearly 7 million patients were diagnosed with CLD in 2013 in the United States and approximately 37% percent or 2.5 million patients received a prescription for an anti-pruritic.

The current antipruritic therapies, primarily antihistamines and corticosteroids as well as other therapies tried off-label, are largely ineffective in treating the disease and/or produce significant side effects. Because of this, there is a significant unmet need for a novel therapy that is effective in treating CLD associate pruritus particularly in patients for chronic cholestatic disease.

The Need for a Novel Therapy for CLDaP

There has been very little innovation in pharmaceuticals that specifically treat patients’ pruritus or itch over the last 50 years. The mainstays for treating itch today are still corticosteroids and antihistamines. The first corticosteroids and antihistamines (like diphenhydramine or Benadryl) were discovered and launched in the 1940s. There have been modest improvements in these drug classes in the subsequent years, but the products utilized today are very similar in action and side effects as those used over 50 years ago.

Although the pathogenesis of CLD-aP remains poorly understood, it is likely multifactorial including evidence for an imbalance in the endogenous opioid system driven by higher mu receptor activation (pruritic) versus kappa receptor activation (antipruritic). Consequently, the use of current anti-pruritic medications is largely ineffective as they do not help with this imbalance.

The patients who live with chronic liver disease associated pruritus or itch and the clinicians who treat it are desperately in need of a new novel antipruritic that will work differently than traditional anti-pruritics to provide itch relief without the significant side effects one finds in today’s medicines.

Cara Therapeutics is developing a novel therapy to change the way chronic liver disease associated pruritus (itch) is managed. Cara is developing a completely new class of medicine called kappa opioid receptor agonists. Kappa agonists target a completely different receptor in the body, the kappa receptor, to treat itch in a new way. Our lead pipeline product, KORSUVA (difelikefalin) is a peripherally acting kappa agonist. To date, Cara is studying KORSUVA Tablets in a Phase 2 trial for patients with moderate to severe CLDaP.