Download Important Disclosures About the Peregrine System™ Kit

Chemical Renal Denervation
Update and Future Directions
Tim A. Fischell, M.D., FACC, FSCAI
Professor of Medicine
Michigan State University
Tim A. Fischell, M.D.
I have the following financial disclosures:
Ablative Solutions, Inc.
Founder, Co-Inventor
Officer and Stockholder
Abbott Vascular
Member, Medical Advisory Board
Important Disclosures About the Peregrine
System™ Kit
THE PEREGRINE SYSTEM KIT IS:
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An investigational product not currently approved in the United States
Limited to investigational use in clinical trials
Currently being studied as a combination drug/device product to evaluate safety and effectiveness for renal
safety and effectiveness for renal denervation in the TARGET BP I Trial under an investigational new drug
under an investigational new drug (IND) application
This presentation reports clinical data collected with the use of the CE Mark Peregrine System™ Infusion
Mark Peregrine System™ Infusion with a neurolytic agent (dehydrated alcohol) for the treatment of
alcohol) for the treatment of patients with systemic hypertension
This presentation is intended solely to aid in scientific discussion and exchange surrounding the
exchange surrounding the development and further evaluation of the product for this use
Post-Symplicity HTN-3 Analysis Suggests
Design Flaws and “Inadequate Denervation”*
Findings from Report
 Renal denervation will work only
if sufficient ablation is provided
 50% of patients did not
receive the minimum of eight
total ablations
 Adequate treatments (9-10
ablations/artery) with RF requires
a vessel length of at least 4-5 cm
 The majority of patients don’t
have vessels this long
* Cardiology News: Renal denervation Proceeds as U.S. Trial’s Flaws Emerge, June 23, 2014; Kandzari et al, Eur Heart J, 2015
Alcohol-Mediated Denervation via Precise Nerve Targeting Device
Perivascular Sites Where
Device Infuses Alcohol
Expanded View of Device
Infusing Alcohol
Site-specific delivery of alcohol targeted for local nerve inactivation
1. Micro-volume (0.3 mL−0.6 mL) infused directly to the perivascular region
2. Extracellular fluid helps spread alcohol circumferentially in the perivascular region
3. Alcohol activity range self-limited through dilution by extracellular fluid
CAUTION: The Peregrine System kit is currently being studied to evaluate safety and efficacy for renal denervation.
It is an investigational product not approved in the US. Its use is limited to investigational use in clinical trials.
The Peregrine System™ Infusion Catheter is CE Marked, and only for use in the European Union
Alcohol-Mediated Neurolysis: Animation
CAUTION: The Peregrine System kit is currently being studied to evaluate safety and efficacy for renal denervation.
It is an investigational product not approved in the US. Its use is limited to investigational use in clinical trials.
The Peregrine System™ Infusion Catheter is CE Marked, and only for use in the European Union
Patient Treatment via Peregrine in Post-Market Study
CAUTION: The Peregrine System™ Infusion Catheter is CE Marked, and only for use in the European Union
Dose Response/Efficacy
Based on Four Independent Surrogate Markers*
100
4
3.4
80
70
2.7
2.5
60
54
2
50
46
• Norepinephrine: %
3.7
3.6
88
3.5
75
3
MDT Distal RF
78
40
2.5
Current dose
30
28
20
10
0
2
NE Reduction %
1
0.15 ml
0.3 ml
Nerve Quadrants %
0.6 ml
Max Nerve Injury
TH decrease
• % quadrants with
injury: score of 3 or
4 (0 to 4 scale)
score: 0 to 4
scale
• TH decrease:
Maximum
reduction = 4
0.5
0
0
0 ml
reduction relative to
controls
• Nerve injury
1.5
Initial
dose
(%) Norepinephrine Reduction /
Quadrants with significant nerve injury(%)
90
*Fischell, et al.;
Cardiovascular
Revascularization
Medicine, 16, 221-227
(2015)
Alcohol-mediated dose response observed with multiple, independent bio-markers in animal studies
Global Clinical Road Map Summary:
Stepwise Approaches to Evaluate Technology
First-Human-Use
Study (Paraguay)
N = 18
Peregrine System™ Kit
(Peregrine catheter + Alcohol)
Global
RCT double-blinded
2:1 (RDN vs. no RDN)
100 pts
Primary endpoint:
mean 24-hour ABPM at 8
weeks
Safety/Performance
N = 10 pts
Europe
Peregrine System™ Infusion Catheter
(Peregrine catheter + Neurolytic agent e.g. alcohol)
Post-Market Study
Single arm, open label,
0.6 mL alcohol/artery
N = up to 120*
* As per Notified Body guidance
CAUTION: The Peregrine System kit is currently being studied to evaluate safety and efficacy for renal denervation.
It is an investigational product not approved in the US. Its use is limited to investigational use in clinical trials.
The Peregrine System™ Infusion Catheter is CE Marked, and only for use in the European Union
Clinical Trials: FIM and Pre-CE
(N = 28 subjects; 38 procedures; 57 renal arteries)
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Peregrine System™ Infusion Catheter successfully navigated to target site in all renal
arteries, including complex anatomy (short, tortuous segments, etc.)
Device performance appears to be successful during all 38 procedures with 97.3%
device success (1 device failure prior to start of procedure in the FIM)
– All vessels (57 in 28 subjects) treated as intended
Minimal to no sedation during the procedures, with short treatment time: average
time/renal artery = 9 ± 5 min
Minimal contrast (average 67 ± 25 mL/procedure) and radiation exposure (average
10 ± 12 min/procedure).
FIM:
• Systolic Office BP Drop: mean -25 mmHg at 1-M, and mean -22 mmHg at 6-M
Peregrine Study (pre-CE):
– Systolic Office BP Drop: mean -29 mmHg and -37 mmHg at 1-M and 3-M (n=10).
– 24-Hour systolic ABPM drop: mean -12 mmHg and -7 mmHg at 1-M and 3-M, and
was maintained at 12-M (-7 mmHg) (n=10)
CAUTION: The Peregrine System™ Infusion Catheter is CE Marked, and only for use in the European Union.
TCT2016 and on file at ASI.
Angiographic Follow-Up -> No Stenosis*
(n = 57 arteries in 28 Subjects)
Baseline
Baseline
Baseline
Baseline
6 Months
6 Months
6 Months
6 Months
CAUTION: The Peregrine System™ Infusion Catheter is CE Marked, and only for use in the European Union.
*As adjudicated by independent core lab
The “Peregrine Post-Market” Study (Europe)
(Enrollment & Treatment Stage)
A Post-Market Study of Transcatheter Perivascular Renal Denervation
for the Treatment of Hypertension using the Ablative Solutions Inc.
Peregrine System™ Infusion Catheter
Study Designed to Satisfy Requirement of Notified Body
Co-Lead Investigators and
Steering Committee Members
Horst Sievert, MD
Int. Cardiologist
Peter Blankestijn, MD
Nephrologist
Steering Committee Members
Atul Pathak, MD
Hypertensionist
Felix Mahfoud, MD
Int. Cardiologist
CAUTION: The Peregrine System™ Infusion Catheter is CE Marked, and only for use in the European Union
The “Target BP I” Study (Global)
A Multicenter, Double-Blind, Sham-Procedure-Controlled
Trial of Renal Denervation with Alcohol as delivered
by the Peregrine System Infusion Catheter
in Hypertensive Subjects
US: IND allowed by FDA to be initiated in the US – EU: Submission on hold
Co-Principal Investigators (US)
David Kandzari, MD
Int. Cardiologist
Michael Weber, MD
Hypertensionist
Co-Principal Investigators (Europe)
Felix Mahfoud, MD
Int. Cardiologist
Ronald Schmieder, MD
Nephrologist
Global Steering Committee
Maurice Buchbinder, MD
Int. Cardiologist
Mathew Weir, MD
Nephrologist
Atul Pathak, MD
Hypertensionist
Melvin Lobo, MD
Hypertensionist
CAUTION: The Peregrine System kit is currently being studied to evaluate safety and efficacy for renal denervation.
It is an investigational product not approved in the US. Its use is limited to investigational use in clinical trials.
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Summary/Conclusions
Preclinical studies suggest that chemical renal denervation using alcohol, with the
Peregrine System Infusion Catheter appears to provide substantial sympathetic
denervation, with favorable safety profile.
Early clinical studies (FIM and the Peregrine (pre-CE study)) suggested consistent
safety and performance of the Peregrine Catheter.
Anatomical safety at 6-month imaging by Angio and CTA with no apparent evidence
of tear, dissection, or new restenosis in any of the 57 renal arteries treated, as
confirmed by independent core labs
Early data from these clinical studies suggest a signal of efficacy with drop in blood
pressure at various stages of the follow-ups. Larger controlled randomized blinded
studies are needed to validate efficacy.
Patient enrollment continues in the Peregrine Post-Market Study in EU with
treatment at the “new” volume of 0.6 mL/artery, with efficacy and safety data being
collected.
“Target BP I”: FDA allowed initiation of study under its IND in the US and the
company expects to start enrollment in 2017.
CAUTION: The Peregrine System kit is currently being studied to evaluate safety and efficacy for renal denervation.
It is an investigational product not approved in the US. Its use is limited to investigational use in clinical trials.
The Peregrine System™ Infusion Catheter is CE Marked, and only for use in the European Union