options for medical students to follow: the biomedical industries pathway
TRANSCRIPT
Vasilios Papademetriou, MD, DSc, FACC, FACP, FAHAProfessor of Medicine (Cardiology)Georgetown UniversityWashington DC
Options for Medical Students to Follow: The Biomedical Industries Pathway
› I am a cardiologist-Interventional› Professor of Medicine ( Cardiology)› Director of Cardiovascular Research for > 25 years› Have done basic research ( early on)- NIH, VA Medical
Center› Lately Clinical Trials ( Mostly)
– Collaborated with the industry– Part of several NIH , VA sponsored trials
› For the last 5 years I served as a member of the Cardio renal Panel of the FDA ( Approval of new drugs)– Rivaroxaban– Droxidopa etc
A few things about myself
› Develop New Drugs
› Develop New Devices – Diagnostic– Interventional– Sensors– Imaging
Aim of the Industry
New DrugsDiscovery and Development
Test many compounds Mechanism of action Rout of administration etc
Preclinical Research In vitro and in vivo Dosing and toxicity in animal models
Clinical Research FDA ReviewFDA Post-Marketing Safety
Monitoring
Clinical ResearchPhase 1
Dosage & safety 20 to 100 healthy volunteers
Phase 2 Efficacy & side effects Several 100s of people
Phase 3 Efficacy and adverse events 300 to 3,000 people
Phase 4 Safety and efficacy Several 1000s of people
RESEARCH & DEVELOPMENT
Only 1:10 new drugs makes it to the FDA and cost can be up to one BILLION $
New DevicesDevice discovery and conceptPreclinical research-PrototypePathway to approvalFDA ReviewFDA Post_ Marketing
Monitoring
Pathway to approvalFDA established risk-based
classification system Class I Class II Class III
Safety and Efficacy Proof of concept/First in man study Controlled trials
Placebo or sham control studies Outcome data
DEVICE DEVELOPMENT PROCESS
Foreign Medical Graduates:Options in Biomedical
Industries
Work for the Industry
Maximize your potentialOptimize chances for success
Collaborate with the industry
Graduates of the EUC
› As a Physician working in private practice or Academia– Clinical Research ( Phase I,II,III or IV studies)– Investigator initiated projects – sponsored by the industry– Basic research of interest to the industry
› Serve on advisor boards– Help the industry understand clinical implications of their studies– Design the right kind of research– Interpret the results of clinical trials
› Steering committees– Direct and supervise clinical studies– Analyze results– Publish research papers
Collaborate with the industry(Part time job)
› Physicians of DCRI– Robert Calif
› Brigham and Women's Research Center– Mark Pfeffer
› Contributed to the development of many of the drugs we use today:– ACE inhibitors– Beta blockers– Statins– Diabetes drugs
Collaborating with the industry
• Pre clinical testing• Toxicity studies
Drug Development
• First in human study• Proof of efficacy and safety
Proof of concept
• Pivotal study• Phase I, II, III and IV studies
Clinical Development Program
› Research & Development– Invent and test new
therapies– Design and Direct
Clinical Trials› Direct Marketing
– Education– Promotion
Working for the Industry as a Physician
Afferent and Efferent Renal fibers Can affect blood pressure control
Afferent fibers originate from the kidney and transfer signals to the brain
After processing can affect the function of the heart, the blood vessels and the kidney
Efferent fibers transfer signals from the brain to the kidney and can affect Na and fluid absorption, plasma renin activity and aldosterone production
SYMPATHETIC RENAL DENERVATION CONCEPT
Papademetriou et al. Circulation 2014;129:1440-51
FIRST IN MAN STUDY: SYMPLICITY HTN-1
1 month(n=41)
3 months(n=39)
6 months(n=26)
9 months(n=20)
12 months(n=9)
-30
-20
-10
0
10
-14 -21 -22 -24 -27-10 -10 -11 -11 -17
SystolicDiastolic
MeanChange in
Blood Pres-sure
(mmHg)Presented
with 95% Con-fidence Inter-
vals
Lancet 2009
RENAL DENERVATION SYSTEMS WITH CE MARK APPROVAL IN EUROPE
ST JUDE MEDICAL RENAL DENERVATION SYSTEM
STAGES OF RENAL DENERVATION
Papademetriou, Tsioufis, Doumas…… Circulation 2014;129:1440-51
LESION PATTERNS USING THE ENLIGHTEN SYSTEM
NOREPINEPHRINE REDUCTION
16
R e n a l n e r v e a b l a t i o n u s i n g t h e E n l i g H T N a b l a t i o n s y s t e m s h o w s s i g n i f i c a n t r e d u c t i o n i n k i d n e y N E a t t h e 3 0 a n d 9 0 d a y t i m e p o i n t s v s . S h a m P TA B a l l o o n ( N = 3 0 k i d n e y s )
65% reduction
Average sys to l ic b lood pr essur edur ing contr o l (CON) and for 8 weeks a f ter rena l
denerva t ionCorre la t ion between SBP and mean
and renal t issue norepinephrine (NE) levels
CATHETER-BASED RADIOREFREQUENCY RENAL DENERVATION LOWERS BLOOD PRESSURE
IN OBESE HYPERTENSIVE DOGS
Each bar represents the average of 7 days of blood pressuremeasurements, 18 hours a day
NEPI change: -42%
ENLIGHTN I: 12 MONTH DATA
Papademetriou V, Tsioufis C,,,,,,,,Hypertension 2014Worthley S, Tsioufis C……Papademetriou V; EHJ 2013
Almost two decades ago the 4S first showed that simvastatin effectively improve survival in patients with cardiovascular disease (CVD), and initiated a revolution in the treatment of atherosclerotic heart disease
Results with other statins confirmed and enhanced these resultsOther newer and/or novel compounds were abandoned either because of
lack of efficacy or unacceptable side effectsRecently ezetimibe-in the IMPROVE-IT study- showed further
improvement of outcomes when added to a statin.Yet the incremental reduction of LDL-C was modest and
additional benefits small, but the study confirmed the impression that “ Lower is better”
That’s where PCSK9 come into play
MANAGEMENT OF DYSLIPIDEMIAS AND PCSK9 INHIBITORS
“Are considered a breakthrough in the management of dyslipidemias because”Are safe andVery-very effective
WHY ARE PSCK9 INHIBITORS IMPORTANT?
SAFE BECAUSE ARE HUMANIZED MONOCLONAL ANTIBODIES
HOW LDL PARTICLES ARE CLEARED
PSCK9 TAGS LDL-R FOR DESTRUCTION
EVOLOCUMAB BINDS TO PCSK9PREVENTING IT FROM BINDING THE LDL RECEPTORS
CARRIER WITH THE INDUSTRY
Graduated from the School of Pharmacy
Graduated from Medical school Specialized in Internal
Medicine Practiced for 10 years Finally Joined Astra Zeneca as
a Scientist-Medical Leeson Works in that position ever
since Lives a comfortable-fulfilling
Interesting lifeMedical Leeson specialist with Astra Zeneca
BRIGHT EXAMPLES Aris Baras MD
Graduated from London high School Duke college Duke Medical Worked on his MD/MBA dual degree at
Duke University. As an undergraduate at Duke, he studied biology and economics. Aris has been fascinated with pursuing biomedical discoveries and the development of life-saving therapies since he was in high school. One of Aris’ mentors has been Dr. Roy Vagelos, former CEO and chairman of Merck. Aris lives in Durham, North Carolina with his wife, Lia, and their son, Parker.School
Joined Regeneron 2years ago, his already a multimillioneur
Through my association with Dr. Roy Vagelos, I started working with the translational medicine team at Regeneron. One of the group’s functions is to thoroughly vet drug candidates before embarking on risky and expensive investments in clinical development programs
LEADING WITHIN THE INDUSTRY Graduated Medical School in Athens
Greece Scholarship at the NIH. Worked and
discovered the gene for Parkinson’s disease
Recruited by Novartis and worked as a researcher for a few years on Gene targeted therapies
Recruited to start his own biotech company
Formed VANDA pharm Developed and sold first drug for
$570 million
Vanda Pharmaceuticals Reports Preliminary Fourth Quarter and Full Year 2015 Results and 2016 Financial Guidance- Fourth quarter 2015 HETLIOZ® net product sales are expected to be approximately $15.1 million
- 2015 Total revenues are expected to be approximately $109.9 million
- 2016 Total revenues are expected to be between $143 and $153 million
REACHING THE TOP George Yancopoulos, MD, PhD of Greek origin, Founding scientist, President and CEO of Regeneron. Graduated from Columbia Un and
Joined Regeneron in 1989 11th most highly cited scientists in the
word in the 1990s He was the PI and got approval of 4
drugs ( aflibercept, ziv-aflibercept,rilonacept and alirocumab)
He is now the highest paid Chief executive
His Company is worth more than $48 billion
The quality of Regeneron science has been recognized in the academic scientific community as well as through a very tangible metric: our four FDA-approved products, as well as every one of our clinical candidates, were discovered and validated in Regeneron's labs. Regeneron Genetics Center ,Target Discovery , Drug Candidate Platforms, Protein Production -