Transcript Harnessing the Inflammatory Reflex: Using Neuromodulation as a

Harnessing the Inflammatory Reflex:
Using Neuromodulation as a Novel Approach to
Treat Chronic Inflammatory Diseases
R Zitnik, Y Levine, M Faltys, T Arnold
SetPoint Medical Corporation, Valencia, California
12/7/12
North American Neuromodulation Society Meeting 2012
1
Inflammatory Disorders Have Significant Morbidity
and Mortality- Medical Need Remains High
Inflammatory Bowel Disease:
Crohn’s and Ulcerative Colitis
•
•
•
•
Rheumatoid Arthritis
Psoriasis, Ankylosing Spondylitis,
Psoriatic Arthritis, Lupus
Common disorders- up to 2% of population
Affects young and middle aged adults
Severe, “life-impacting” symptoms
Systemic inflammation associated with highly elevated
cardiovascular mortality risk
12/7/12
North American Neuromodulation Society Meeting 2012
2
Current Drugs and Biologics are an Important
Advance- Yet Have Major Drawbacks
• Lack of efficacy in 1/3 (RA) to 2/3 (Crohn’s)
• Rare but serious safety issues: Infection, TB, CHF, cancer risk,
MS, PML, hypercholesterolemia
• $30 billion in annual sales with per patient cost of $25-35K/year
Goal is to improve the treatment of these
diseases using neuromodulation
12/7/12
North American Neuromodulation Society Meeting 2012
3
CNS Regulates the Immune System via the
“Inflammatory Reflex”
• Afferent vagus and CNS sense inflammatory
mediators (should this read: CNS senses
inflammation via the afferent vagus)
• Efferent vagus signals resident T cells and
macrophages in the spleen and GI tract
• Pro-inflammatory cytokine production reduced
• Circulating immune cells traversing the spleen
are altered:
• Reduced capacity to express inflammatory
mediators and adhesion molecules as cells
move into diseased tissue
In inflammatory diseases,
activity of pathway is
decreased
Tracey, Cell 2012
Rosas-Ballina, Science 2011
12/7/12
North American Neuromodulation Society Meeting 2012
4
Stimulating this Reflex Using Neuromodulation will
Reduce Inflammation and Improve Clinical Disease
Rheumatoid Arthritis
Inflammatory Bowel Disease
Andersson U, Tracey K.
Ann Rev Immunol 2012; 30:313
12/7/12
North American Neuromodulation Society Meeting 2012
5
VNS Lead for Rodent Inflammation Models
12/7/12
North American Neuromodulation Society Meeting 2012
6
Joint Swelling Was Reduced in Standard CollagenInduced Arthritis Model
•Bolder BioPATH, Inc.
•n=4/Normal Controls
•n=12/disease control
•n=9/ stimulation group
•*p≤0.05 t-test to Disease Controls
12/7/12
North American Neuromodulation Society Meeting 2012
7
Importantly, Structural Damage to the Joint was Also Reduced
•Bolder BioPATH, Inc.
•n=12/disease control
•n=9/ stimulation group
•*p≤0.05 t-test to Disease Controls
*
*
12/7/12
*
North American Neuromodulation Society Meeting 2012
*
8
Clinical Study of Neuromodulation in Rheumatoid
Arthritis
“Methotrexate Failure” Population
• Active RA despite treatment with first line agent methotrexate
• Patients would otherwise have been candidates for a TNF antagonist
Standard RA clinical endpoints:
• DAS28 (Tender and Swollen Joint score, CRP, Patient VAS)
• ACR 20/50/70 Response Rate
• EULAR Response and Remission Rate
Commercially purchased VNS devices were used for the study
12/7/12
North American Neuromodulation Society Meeting 2012
9
Individual Patient DAS Scores Show Rapid and
Marked Improvement in 6 of the 8 Subjects
EULAR Remission
12/7/12
North American Neuromodulation Society Meeting 2012
10
Clinical Response Rates are Comparable to
Those Seen with Biologics
12/7/12
North American Neuromodulation Society Meeting 2012
11
Future Studies Will Utilize SetPoint’s
Proprietary Neuromodulation Platform
Surgical Implant
MicroRegulator
Patient Charger
12/7/12
Pod
Prescription Pad
North American Neuromodulation Society Meeting 2012
12
Summary and Conclusions
• Inflammatory diseases are a $30B market with significant unmet need
• Using neuromodulation to drive the inflammatory reflex has a sound
biological foundation: Use in clinic is supported by strong preclinical
evidence
• This is the first demonstration that an implantable neuromodulation
device improves clinical manifestations of RA:
• Significant and clinically meaningful improvement in signs and symptoms
• Response rates were comparable to those with current biologic agents
• Further larger controlled studies in RA and other chronic inflammatory
diseases are warranted.
• Our microregulator offers significant advantages over current vagal
nerve stimulation devices
SetPoint intends to offer a novel therapy that will significantly increases patient
QOL, while bending per-patient cost curves down by more than 60%
12/7/12
North American Neuromodulation Society Meeting 2012
13