Big placebo response rattles Cara ahead of pivotal tests

Cara Therapeutics scored a win earlier this year in the first pivotal study of its anti-itch project, Korsuva, raising hopes for a similarly positive readout from a confirmatory trial early next year. But investors were given reason to fret today: a surprisingly marked placebo response almost derailed a mid-stage study of a follow-on oral formulation of Korsuva, causing several secondary endpoints to be missed. The more advanced Korsuva asset is intravenously administered, and the company suggested that awareness of that project’s phase III success could have contributed to an “anomalous” placebo effect in the phase II study. Executives had no firm theory for the finding, however, pointing out that this was the first pruritus study to be conducted in a chronic kidney disease setting, making findings more unpredictable. The chance of similarly high placebo responses being seen in either the second phase III study of the IV formulation or future pivotal studies of the oral project were firmly rebuffed. Investors were not convinced: shares in Cara fell 27% in early trade today. The stock touched a record high at the end of November, so perhaps some profit taking on today’s result was inevitable.

Cross-trial comparison of Korsuva clinical trials
  Kalm-1 (dialysis patients) CKD phase II 
  Korsuva (n=189) Placebo (n=189) 1mg (n=67) placebo (n=67)
Change from baseline in weekly mean WI-NRS  -3.1 -2.0 -4.4 -3.3
  n/a p=0.018
≥ 3 improvement in WI-NRS at week 12 51%* 28% 72% 58%
  p=0.000019 p=0.110
*Primary endpoint. WI-NRS = Worst Itching Intensity Numeric Rating Scale. Source: Company presentations, NEJM. 

 

Cara's pruritis programme

Study

Enrollment NCT ID Notes
Phase 3      
KALM-2 IV Korsuva in dialysis patients 250 NCT03998163 Data due Q1'20
KALM-1: IV Korsuva in dialysis patients 378 NCT03422653 Reported positive topline results
Phase 2      
Oral Korsuva in primary biliary cholangitis  60 NCT03995212 Data due 2020
Oral Korsuva in atopic dermatitis  240 NCT04018027 Data due 2020
Oral Korsuva in chronic kidney disease  271 NCT03617536 Hit primary endpoint, missed secondary
Source: EvaluatePharma.       

 

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