Background: CD-NP, a chimeric natriuretic peptide, with veno-arterial vasodilation may simultaneously unload the heart and kidney in acute decompensated failure (ADHF) patients. This dose-ranging study investigated the safety and tolerability of CD-NP in ADHF patients (pts).
Methods: ADHF pts with renal compromise, treated with at least one dose of furosemide, were randomized to either active CD-NP or placebo.
Inclusion criteria were symptomatic ADHF with NT-pro-BNP level >= 1400 pg/mL, systolic blood pressure (SBP) >=105-180 mmHg, and renal compromise with creatinine (Cr) clearance of 30-80 mL/min. CD-NP was infused for at least 48 hours at 1.25, 2.5, 3.75, or 5 ng/kg/min and placebo. Serial measurements of blood pressure and renal function were performed.
Results: Baseline characteristics shown in table below. There appeared to be a dose-dependent mean maximum SBP reduction compared to placebo. The 5 ng/kg/min dose of CD-NP was aborted due to clinically-relevant blood pressure reduction. Serum Cr level in the 1.25, and 2.5 groups improved relatively to the placebo cohort by the end of infusion. Plasma cystatin-C level at 1.25, 2.5, and 3.75 doses of CD-NP showed relative
improvement compared to placebo by the end of infusion period.
Conclusions: CD-NP appeared to be well tolerated. Dose-dependent mean maximum SBP reduction observed. CD-NP at 1.25 and 2.5 ng/kg/min
appeared to preserve renal function relative to placebo as measured by renal biomarkers.
Age, % men : 67.1 ± 10.6, 70%
Baseline SBP ± SD : 133 ± 17
Baseline Cr (mg/dL) ± SD : 1.32 ± 0.4
Mean maximum SBP change, mmHg ± SD : -21 ± 21
Change in Cr at end of infusion, mg/dL ± SD : 0.05 ± 0.26
Change in cystatin-C at end of infusion, mg/dL ± SD : 0.07 ± 0.12
1.25 ng/kg/min CD-NP
Age, % men : 69.4 ± 11, 80%
Baseline SBP ± SD : 142 ± 20
Baseline Cr (mg/dL) ± SD : 1.46 ± 0.7
Mean maximum SBP change, mmHg ± SD : -24 ±12
Change in Cr at end of infusion, mg/dL ± SD : -0.01 ± 0.28
Change in cystatin-C at end of infusion, mg/dL ± SD : -0.05 ± 0.24
2.5 ng/kg/min CD-NP
Age, % men : 66 ± 16.8, 70%
Baseline SBP ± SD : 133 ± 11
Baseline Cr (mg/dL) ± SD : 1.38 ± 0.4
Mean maximum SBP change, mmHg ± SD : -27±12
Change in Cr at end of infusion, mg/dL ± SD : -0.06 ± 0.20
Change in cystatin-C at end of infusion, mg/dL ± SD : 0.0 ± 0.15
3.75 ng/kg/min CD-NP
Age, % men : 71.6 ± 13.8, 80%
Baseline SBP ± SD : 137 ± 18
Baseline Cr (mg/dL) ± SD : 1.32 ± 0.4
Mean maximum SBP change, mmHg ± SD : -34 ± 20
Change in Cr at end of infusion, mg/dL ± SD : 0.10 ± 0.33
Change in cystatin-C at end of infusion, mg/dL ± SD : 0.02 ± 0.27
One thing is clear. This data is not bad.
Whether it is good or not ? It requires lareger trails to know. If nile can prove that this drug does not increase the s. creatinine and treats the heart failure, then this will be block bluster diuretics for acute heart failure
With diuretics in the heart failure, biggest problem is increase in the s. creatinine after the IV diuretics. Increase in s. creatinine is associated with worse out come.
This is a NEW molecule - C peptide + D peptide. D peptide is associated with renal protection.
looks like FDA is interested in new molecule as they had given a fast track status for out patient indication.
This data is from the inpatient trial.
Next step for the Nile is to find a partner and do the Phase II B trial.
Most likely they will test 1.25 and 2.5 ng/kg/min dose against the placebo.
Market for the new molecule in the acute heart failure is very big.
Nile has a good management - Nile's executive chairman is DNDN chairman of board.
They have partnered with Medtronic for out patient indication. medtronic is like a EXXON ( oil company ) of cardiology products.
Zack investment is putting target of 2 +, and On stockcharts.com target is around $ 6.38.
stock market is like a popularity contest. Once this stock gets more press then it will gain more. It is already up after the fast track announcement.
Once we hear about the nile's dicussion with FDA for inpatient indication ( which happenend earlier this year ) and partnership then value should go up.