Cara Placing Korsuva Hopes On Oral Formulation, Broad Pruritus Label
Executive Summary
I.V. Korsuva now has an August FDA action date, which partner Vifor would commercialize in the ESRD dialysis setting while Cara works toward a broad anti-pruritus label for its oral tablet formulation.
Cara Therapeutics, Inc. has been in existence since 2004 and is focused almost entirely on the internally discovered Korsuva (difelikefalin), which could see its first approval with a 23 August action date at the US Food and Drug Administration for an intravenous formulation to treat pruritis in chronic kidney disease – but Cara is looking at bigger opportunities down the road for an oral formulation of the first-in-class kappa opioid receptor agonist.
If it's approved, partner Vifor Pharma Group will commercialize I.V. Korsuva to treat pruritus in chronic kidney disease patients on dialysis therapy under a profit-sharing arrangement. Cara CEO Derek Chalmers told Scrip his firm will commercialize the oral product, hopefully in patients with chronic moderate-to-severe pruritus due to multiple causes. The Stamford, CT-based firm anticipates data from a Phase II, dose-ranging study of oral Korsuva in pruritus associated with atopic dermatitis during the first half of 2021, and if positive will initiate a pivotal Phase III study.
The two companies announced the FDA’s acceptance of the I.V. Korsuva new drug application on 8 March, with priority review setting a user fee date of 23 August. Cara also noted that the agency said it does not plan an advisory committee to review the filing. Korsuva is an internally discovered drug that Cara hopes will provide better efficacy against pruritus compared to older classes of drugs such as steroids and Janus kinase inhibitors. (Also see "Cara’s Phase III Success In CKD-Pruritus Puts NDA Filing In Sight" - Scrip, 29 May, 2019.)
The NDA is backed by two successful Phase III studies – KALM-1 in the US and the international KALM-2 – that demonstrated statistical significance for reducing worst itch rating compared to placebo after 12 weeks. (Also see "Cara’s Korsuva Impresses Against Pruritus In Hemodialysis Patients" - Scrip, 21 Apr, 2020.) Cara reported the KALM-1 data in May 2019 and the KALM-2 data in April 2020.
As Cara studies the oral formulation to treat pruritus in pre-dialysis CKD, the liver disease primary biliary cholangitis, atopic dermatitis and a neuropathic condition called notalgia paresthetica (itch of the upper-middle back), Chalmers said his company views Korsuva potentially as a pipeline in a product. The drug acts directly on the pruritus pathway inhibiting activity that transmits the sensation of itch and also blocks cytokines that drive pruritus in relation to various forms of pathology, he said.
“Because of that mechanism of action, we see Korsuva having broad applicability regardless of the initiating pathophysiology,” the exec said, “so that’s a significant number of patients. We estimate based on prescriptions here in the US, some 20 million patients suffer from chronic pruritus.” While the first pivotal study of oral Korsuva likely will be in atopic dermatitis – pre-dialysis CKD is the second most advanced setting at present – Cara’s goal is a label for broad anti-pruritus efficacy regardless of cause, he added.
“The idea is we’re working through our patient populations according to FDA guidance and seeking labeling for those patient populations, so first we’re seeking treatment of moderate-to-severe pruritus in atopic dermatitis patients,” Chalmers said. “But ultimately, and we designed our clinical trials this way, we hope to show efficacy broadly across the major categories of pruritus.”
Cara Will Leverage Vifor’s Existing Dialysis Infrastructure
Cara first partnered with Vifor in 2018 to have the Swiss firm commercialize I.V. Korsuva for dialysis patients in Europe, South America and Asia-Pacific except for Japan and South Korea. Last fall, the companies revised the pact giving Vifor commercial rights in the US as well, so that Cara could benefit from the drug’s expected first indication without needing to build a nephrologist-directed sales force from scratch on its own, Chalmers explained.
Cara got $70m up front under the original agreement, with potential for up to $470m in milestone payments and double-digit sales royalties in Vifor’s territories. The revised deal agreed to last October specifies both that Vifor will use Korsuva in its US dialysis facilities and also market the product to other US dialysis providers, with Cara getting 60% of the profits and Vifor keeping the remaining 40%. Cara also got $100m up front plus a $50m equity investment from Vifor under the new agreement.
“We thought it might make sense strategically to leverage what was already established in Vifor’s sales force rather than building a commercial infrastructure for Cara that was really going to be focused on the nephrology market, which is not where we see the broader applicability in the long run with the oral tablets,” Chalmers said.
“We get to leverage not only Vifor’s commercial infrastructure and their distribution network, but we get to leverage their already established relationships with dialysis providers across the US,” he continued. “I think that will really add momentum to the launch and to the adoption of Korsuva into dialysis clinics.”
The first two years after US approval of Korsuva for the dialysis setting could be particularly lucrative for the two firms because the Centers for Medicare and Medicaid Services exempt novel products from being part of the ESRD payment bundle for their initial two years on market. Chalmers said Cara thinks it may have an argument that additional payments be added to the ESRD bundle following those first two years since there is no currently approved therapy for dialysis-associated pruritus in ESRD patients.
Chalmers said that while Cara is glad to let Vifor commercialize Korsuva in the dialysis setting, it sees no inconsistency in its strategy to market the product to pre-dialysis CKD patients. If the company succeeds in getting the broad label it is seeking, he anticipates Cara will mainly market oral Korsuva to dermatologists, endocrinologists and primary care physicians.
Analysts generally have expressed enthusiasm for Korsuva and for Cara’s longer-term strategy. In notes following the company’s 25 February quarterly earnings call, Piper Sandler analyst David Ansellem called the drug “a potentially $1bn-plus franchise across a range of pruritic settings,” while Chris Howerton of Jefferies said Korsuva could have up to $5bn in peak sales. Howerton also predicted a high probability of statistical success for Korsuva in the Phase II atopic dermatitis study.