October 24, 2015 www.PreferredRegulatoryConsulting.com

25 years TCT • Structural heart dominated TCT 2015 - focus is shifting to

the mitral space

• mitral regurgitation is yet to be solved - diverse etiology

needing diverse solutions

• buying frenzy: 5 large acquisitions in 2015 - total of >$2B

• Bioresorbable stents take a center stage - DES only

mentioned as comparator

• not all bioresorbable stents are the same - physicians are

learning how to apply them

• long term 5 year data are not yet available, but physicians

are hopeful

• use in pediatric patients

• Drug delivery into vessels

• Drug-coated balloons for PAD and CAD - the more

doctors use them, the more they like them

• Paclitaxel is great, but can “olimus” play role in DCBs?

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2015 Issue 10

NEWSLETTER

What is new and what is tried and true?

October 24, 2015 www.PreferredRegulatoryConsulting.com

• Novel drug delivery approach took the Main Arena stage

for a life case

• Digital Health - wearables, smart phone accessories, home

based, patient centric health data collection

• FDA was in town for 2 days: early feasibility studies

program still in its infancy but seems to be working;

interactive open dialogue facilitated by new processes and

guidances

Detailed Review Structural Heart sucked the oxygen in the room

• Everyone was talking about innovative structural heart

technologies, but mitral regurgitation was front and

center

• Dr. Martin Leon from Columbia set the tone for the

importance of transcatheter valve replacement and the

need to innovate more in the space to address the

various etiologies of mitral regurgitation

• Cardiac surgeon Dr. Michael Mack from Plano, TX was co-

chair in many of the discussions and brought in the

surgeon’s perspective to transcatheter valve technologies

• In several sessions, Dr. Mack presented transcatheter

mistral valve technology development and current

status - in 2015, 5 large acquisitions; over $2B spend

by large companies to obtain new transcatheter mitral

valve technologies

• In the US, MitraClip is still the only transcatheter mistral

regurgitation solution approved ONLY for degenerative

MR

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TCT2015 in Pictures

October 24, 2015 www.PreferredRegulatoryConsulting.com

• COAPT trial for functional MR is ongoing - Dr. Mack

and Dr. Leon are co-PIs; enrollment is slow due to very

complex enrollment criteria, 85 center with ~289

patients; data expected late 2017

• 25,000 MitraClips worldwide for both FMR (majority)

and DMR

• Valve-in-valve technique is further developing due to the

need to remediate failed surgical valves

• the type of the surgical valve in place is key to the

success of the valve-in-valve procedure

• if the failure is due to a rigid band, it will deform the

shape of the TAV

• Patient selection for TMVR is key, similar to TAVR

• Advantages and disadvantages of different assess

techniques were presented by Dr. Nicolo Piazza:

• Transapical - most of the devices use this approach

• Transfemural - not a straight shot

• Best sizing of mitral valve is with 3D transesophageal

Echo

• Tricuspid valves are gaining traction with one product

being approved for early feasibility study (EFS) in the US

• Minimally invasive bands, like the Cardioband work well

and are easy to implant even via a transfemural approach

Digital Health: • It is not simply a buzz - it is real and the need for wider

adoption of mobile technologies is required to drive cost

down and to allow patients access to their own data

• Dr. Gregg Stone advocated the need for a national health

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Aortic valves are from Mars and mitral valves are from

Venus!

October 24, 2015 www.PreferredRegulatoryConsulting.com

identification system compatible with EHR to acquire health data and use for health

management, trending and prevention

• Major trend in the US is to do more post-marketing studies and collecting big data would

help identify trends

• Consenting patients is an issues in the way of big data

Drug delivery into the vessel wall: we have moved beyond DES • Bioresorbable scaffolds (BRS):

• making them and using them is an art and takes learning

• new and aged BRS behave differently and physicians need to learn how to use them;

new scaffolds tend to stretch more compared to aged

• use of OCT to better determine the lesion diameter

• they have a place in young patients, especially pediatric patients - a fascinating life

case in 1.5 month old baby

• early data are comparable with the best in class DES, but the hope is that at 5 years,

late loss and TLR will be improved in BRS compared to DES

• three year BRS data indicate that the scaffold is completely gone and long term

benefits are better than those with metallic stents

• Bottom line: BRS is not just another DES, but provides new possibilities to treat where

DES was not used before

• Drug coated balloons: main use is still in PAD; some

CAD data were presented

• majority of the currently approved DCB contain

paclitaxel - once in the tissue, it reins there slowly

eluting and preventing local inflammatory reaction

• Dr. Juan Granada from CFR presented data on an

“olimus” containing DCB - the issue with “olimus” is

that once it is off the balloon, it tends to rapidly

metabolize and disappear from the tissue and blood,

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Preferred Regulatory Consulting specializes in cardiovascular products (stents, balloons, drug

delivery and visualization) and assists clients with FDA

submissions and negotiations

October 24, 2015 www.PreferredRegulatoryConsulting.com

hence - no sustained release; novel DCB is

attempting to solve this pharmacokinetic issue

• Novel drug delivery injection device was demonstrated

in a life PAD case on the Main Arena

FDA Townhall: • Day 1: Jeff Shuren outlined CDRH's vision

• Risk/benefit analysis is front and center

• Dr. Jeff Shuren expressed FDA’s desire to be the first

agency world-wide to approve novel devices;

• Dr. Bram Zuckerman encouraged industry to talk to

FDA "early and often";

• Dr. Andrew Farb summarized the current status of

the early feasibility study program

• Main FDA achievement to facilitate fasted access of

US patients to novel technologies:

• 2014 was the best PMA year, when the most PMAs

were approved

• Early Feasibility Studies (EFS) - 6 studies in the area

of structural heart: sponsors and investigators are

impressed with FDA’s responsiveness

• Major OUTSTANDING challenges to conduct clinical

studies in the US:

• IRB review and approval; Site contract and budget

negotiations - FDA is no longer the bottleneck -

the sites’ internal bureaucracies are now what stays

between new technologies and patients

• CMS does not reimburse for procedures done

under an early feasibility study, putting financial

burden on startups

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FDA Townhall in Pictures

October 24, 2015 www.PreferredRegulatoryConsulting.com

• New term developers need to know: JITT - just in

time testing; don’n commence testing before

actually necessary

• Expedited access pathway (EAP) - 19 approved

since the publishing of the guidance in April 2015

• FDA received industry and investigator praises for

the early feasibility study program.

• Day 2: FDA townhall day 2 revolved around clinical

trial design; proper anticoagulants post stent

implantation

• data from the use of the Watchman device were

presented in light of future studies with similar

devices

• Physicians, CDRH and CDER experts discussed the

use of post-PCI anticoagulants

Other topics at TCT2015: • neurovascular procedures to address stroke

• transfemural vs. transradial access: in the US the % of

transradial procedures is very low (~6%) compared to

other countries but the trend is to change:

• transradial access associated with less bleeding;

• appropriate for some but not all cases

• over the next 10 years in the US transradial access will grow in use

• in the US interventional cardiologists should train for all types of access

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Preferred Regulatory Consulting

thorough-compliant-business oriented

✓Regulatory, Quality, and

Clinical services to medical

device and pharmaceutical

companies at all stages of

their development.

✓Experience obtaining FDA

marketing clearance and

approval.

✓Successful PMA and de

novo submissions.

Therapeutic Areas:

Cardiovascular, ENT,

Bronchial, Urology,

Nephrology, OBGYN,

Neurology, Orthopedics,

Gastroenterology, and

Metabolic Diseases

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