- The company reported positive Phase II clinical results of oral KORSUVA showing a strong efficacy and safety profile compared to placebo.
- Management stated that the response rate of the placebo group was better-than-expected, therefore the drug didn’t achieve statistical significance in all secondary endpoints.
- We believe that the current cash position will be sufficient enough over the next 6-8 quarters.
Cara Therapeutics (CARA) recently reported the top-line results of its phase II clinical study of oral KORSUVA in patients with CKD-associated pruritus. Following the positive phase II clinical trial results, the stock price plunged for almost 35% on December 3, 2019. Our investment thesis is built around the fact that a particular plunge was exaggerated, given that the secondary endpoint of the responder rate didn’t meet statistical significance because of better than expected placebo response. Management will undergo an in-depth analysis of both patients subgroups and types of medication use to try to diminish the placebo response during the next phase III study. We believe that the company is on the right track to receive the first FDA approval for the treatment of CKD-associated Pruritus. The efficacy and safety profile of oral KORSUVA Injection during phase II study was very strong and similar to the results of prior injection KORSUVA studies. Consequently, we find as one of the key bullish catalysts the potential release of positive results from the phase III oral KORSUVA clinical study which will be initiated next year.
Phase II Oral KORSUVA Clinical Study
The Oral KORSUVA Phase 2 study was a 12-week treatment trial that was designed to evaluate the safety and efficacy of 1.0 mcg/kg Oral KORSUVA for CKD-associated Pruritus. The total number of patients in the phase III study was 269 and they were almost equally divided into a placebo group (67 patients) and three groups (67-70 patients per group) receiving Oral KORSUVA treatment in 0.25 mg, 0.5 mg, and 1.0 mg doses. The structure of primary endpoint and secondary endpoints was similar as in the previous injection KORSUVA clinical studies.
“The primary efficacy endpoint was the change from baseline in the weekly mean of the daily 24-hour Worst Itching Intensity Numeric Rating Scale (WI-NRS) score at Week 12 of the treatment period for any of the three tablet strengths vs. placebo. Secondary endpoints included change from baseline in itch-related quality of life scores at the end of Week 12, as assessed by the total Skindex-10 and 5-D itch scales, as well as the proportion of patients achieving an improvement from baseline of ?3 points with respect to the weekly mean of the daily 24-hour Worst Itch NRS score at Week 12.”
(Source: Press Release)
(Source: Investor Presentation)
The primary endpoint was met with a statistical significance of p-value at 0.018, as KORSUVA achieved a -4.4 points reduction in WI-NRS score compared to PLACEBO reduction of -3.3 points after 12-weeks treatment period. According to the figure above, a 1.0mg oral KORSUVA had at least a three?point improvement from baseline starting at week 4 throughout the rest of the study compared to the three-point improvement of placebo starting at week 9. The drug already showed a significant response of itch-intensity reduction in the early stage at week 2 compared to placebo and the greatest divergence compared to placebo was between weeks 4 and 6 which reflects a strong efficacy of the drug.
