Congrats to CARA on a well-executed and positive Phase 3 trial of KORSUVA injection for reduction of pruritis (severe itching) in hemodialysis chronic kidney disease patients. The phase 3 top-line data met the primary endpoint of proportion of patients on KORSUVA achieving at least a 3 point improvement in worst itch from placebo at week 12 (51% vs. 28% (p=0.000019)). Additionally, the trial met all its secondary endpoints as well, which included quality of life measures that the company has reported as important not only to patients, but to the FDA as well. Safety data looked good with diarrhea (9.5% vs. 3.7% placebo) and dizziness (6.9% vs. 1.1% placebo) being the most prevalent adverse events with no patients stopping the trial for diarrhea and most resolving within 1-3 days, and 3 patients stopping for dizziness, the majority of which resolved the same day.
The phase 3 top-line efficacy and safety data were very consistent with the positive Phase 2 data (see graphs below).
Next up for CARA are two interim Data Monitoring Committee powering readouts that are expected this quarter: 1) the international Phase 3 KALM-2 trial in the same indication and otherwise identical to KALM-1; and 2) Interim analysis for Phase 2 trial of oral Korsuva for pruritis associated with kidney disease for patients not on hemodyalisys. CARA's powering interim analysis seem more meaningful with respect to efficacy than most interim readouts because a continuation of the trial without increasing patient numbers not only appears to show no safety issues and that some efficacy is occurring (the trial is not futile) as is common in interim readouts, but also that the efficacy being seen is strong enough to meet its primary endpoint without requiring more patients. Of course, investor caution is always advisable in interim readout go/no-go decisions. Although all of us in biopharma investing get humbled by the unpredictability of clinical trial readouts, it is noteworthy that we published a bullish article on CARA as our top pick for Q1 2019 (CLICK HERE) and again for Q2 (CLICK HERE) based on its impressive phase 2 results and attractive valuation given the market potential for KORSUVA.
Currently, CARA is up around 19% on today's news and over 60% for the year, but we still see plenty of upside (and risk of course) in CARA's upcoming 2019 readouts. For example, although we feel that KALM-2, like KALM-1, has a very good chance of success, there is more risk because of the international nature of KALM-2, and the oral KORSUVA readout will be the first itch efficacy readout for the oral version of the drug, which has more risk than the KALM trials, which repeated phase 2 trials of KORSUVA injections, but opens up a much larger oral market. It will be exciting to watch CARA's progress through the year, not only as investors but especially for the sake of patients suffering from sever itch.
Phase 3 vs. Phase 2 results for KORSUVA injection in CKD
Phase 2 Worst Itch over time (compare to KALM-1 Ph3 results in article above)