Cara, CSL Vifor’s CKD itching drug, backed for NHS use

Some patients in the UK with chronic kidney disease (CKD) who develop chronic itching – one of the most common and challenging side effects of dialysis – will soon be able to access a new therapy from CSL Vifor and Cara Therapeutics.

New guidance from health technology assessment (HTA) organisation NICE means that adult CKD patients in England, Wales, and Northern Ireland will have the option of treatment with Kapruvia (difelikefalin) if they develop moderate to severe chronic itching, or pruritus. A decision on the drug by the SMC – NICE’s counterpart in Scotland – is scheduled for this month.

Kapruvia was approved by the MHRA just over a year ago, becoming the first drug specifically approved for CKD-related pruritus. It adds to various therapies used to treat the condition, including creams and emollients, antihistamines, and gabapentin, which don’t work very well.

NICE’s recommendation is that, if supportive care with these therapies isn’t effective, Kapruvia could then be offered as an add-on. It is administered intravenously three times a week in the dialysis clinic, and the guidance says treatment can continue for the duration of dialysis so long as there is a reduction in itch score within the first 12 weeks.

Around 40% of patients on dialysis for CKD have moderate to severe pruritus, making the new drug an option for an estimated 250,000-plus patients across Europe, and one which analysts at Jefferies have suggested could eventually become a $900 million-a-year product.

The reason dialysis treatment causes itching isn’t well understood. It removes excess water from the body, and limited fluid intake between treatments can lead to dry skin, which may contribute to the problem. Another speculation is that dialysis itself causes chronic inflammation in the body, with itching a manifestation of this process.

How Kapruvia works is also not fully understood. The drug acts as an opioid agonist, targeting the kappa opioid receptors (KORs) in the peripheral nervous system that are thought to be involved in controlling itch and inflammation. It has limited activity against the mu-opioid receptors (MORs) targeted by opioid agonists used for pain relief.

NICE based its decision on two phase 3 trials, KALM-1 and KALM-2, which showed that treatment with Kapruvia resulted in clinically meaningful improvements in pruritus severity and in pruritus-related quality of life.

Kapruvia has also been approved in the EU, as well as the US – where it is sold as Korsuva – and a decision in Japan is due in the second half of this year.

It is still in the rollout phase, having launched in the US, Austria, Germany, Sweden, France, Finland, the Netherlands, Switzerland, and Denmark, according to Cara’s first-quarter results update. US sales reached $35 million last year.

Cara and Vifor are also testing oral difelikefalin in pre-dialysis CKD patients, which could expand the market for the drug significantly, with phase 2 top-line results due next year. The oral version is also being trialled in atopic dermatitis and notalgia paresthetica.