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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. - PowerPoint PPT Presentation
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North American Neuromodulation Society Meeting 2012
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
112/7/12
North American Neuromodulation Society Meeting 2012
Rheumatoid ArthritisInflammatory Bowel Disease: Crohn’s and Ulcerative Colitis
Psoriasis, Ankylosing Spondylitis, Psoriatic Arthritis, Lupus
Inflammatory Disorders Have Significant Morbidity and Mortality- Medical Need Remains High
• 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
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North American Neuromodulation Society Meeting 2012
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
312/7/12
Goal is to improve the treatment of these diseases using neuromodulation
North American Neuromodulation Society Meeting 2012
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
412/7/12
Tracey, Cell 2012
Rosas-Ballina, Science 2011
In inflammatory diseases, activity of pathway is
decreased
North American Neuromodulation Society Meeting 2012
Stimulating this Reflex Using Neuromodulation will Reduce Inflammation and Improve Clinical Disease
Andersson U, Tracey K.
Ann Rev Immunol 2012; 30:313
Rheumatoid Arthritis Inflammatory Bowel Disease
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North American Neuromodulation Society Meeting 2012
VNS Lead for Rodent Inflammation Models
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North American Neuromodulation Society Meeting 2012
•Bolder BioPATH, Inc.•n=4/Normal Controls•n=12/disease control•n=9/ stimulation group•*p≤0.05 t-test to Disease Controls
Joint Swelling Was Reduced in Standard Collagen-Induced Arthritis Model
712/7/12
North American Neuromodulation Society Meeting 2012
•Bolder BioPATH, Inc.•n=12/disease control•n=9/ stimulation group•*p≤0.05 t-test to Disease Controls
*
**
*
Importantly, Structural Damage to the Joint was Also Reduced
812/7/12
North American Neuromodulation Society Meeting 2012
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 antagonistStandard RA clinical endpoints:•DAS28 (Tender and Swollen Joint score, CRP, Patient VAS)•ACR 20/50/70 Response Rate•EULAR Response and Remission RateCommercially purchased VNS devices were used for the study
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North American Neuromodulation Society Meeting 2012
Individual Patient DAS Scores Show Rapid and Marked Improvement in 6 of the 8 Subjects
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EULAR Remission
North American Neuromodulation Society Meeting 2012
Clinical Response Rates are Comparable to Those Seen with Biologics
1112/7/12 1112/7/12
North American Neuromodulation Society Meeting 2012
Future Studies Will Utilize SetPoint’s Proprietary Neuromodulation Platform
MicroRegulator Pod
Patient Charger Prescription Pad
Surgical Implant
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North American Neuromodulation Society Meeting 2012
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%
1312/7/12