MEDICAL DEVICE DAILY
TM
THE DAILY MEDICAL TECHNOLOGY NEWS SOURCE
MONDAY, APRIL 28 , 2014
VOLUME 18, NO. 80
FDLI ANNUAL MEETING
FDA approves first HPV test for
primary cervical cancer screening Consultant: Interest in companion
By Amanda Pedersen, Senior Staff Writer
The FDA has approved the cobas HPV (human papillomavirus) Dx ‘waning,’ says payers skeptical
test from Roche (Basel, Switzerland) as a first-line primary
screening test for cervical cancer in women 25 and older. The
approval follows the March 12 unanimous recommendation from
the Microbiology Devices Panel of the FDA’s Medical Devices
Advisory Committee, making the cobas the only HPV test in the
U.S. approved for first-line primary screening. Previously HPV
tests had been used as a follow-up test for Pap (Papanicolaou)
results and as an adjunct to Pap in women over 30.
The Pap test has been the primary screening tool for cervical
cancer for the last 60 years and for about the last 15 years
clinicians have been testing with both the Pap and an HPV test.
See Roche, page 4
COME ON OVER!
Neural prosthesis doubles as
an electroporation device
By Anette Breindl, Science Editor
Researchers have come up with an unusual variation of the
theme of drug-device combinations. They have used cochlear
implants as electroporation devices to enable gene therapy
during implantation, which in turn stimulated nerve outgrowth
that allowed the implant to perform better.
The team published their animal studies in the April 24,
2014, issue of Science Translational Medicine.
Electrical current can be used to briefly increase the
permeability of cell membranes for gene delivery. Companies
like Inovio Pharmaceuticals (Blue Bell, Pennsylvania), MaxCyte
See Neural, page 6
WASHINGTON — We are often reminded that nobody said it
would be easy, but firms interested in the companion diagnostic
space might also
saying “nobody
Washington roundup, p. 2 be
said it would be this
tough,” according
to a consultant. Karen Becker, PhD, managing director for
translational and regulatory sciences at Precision for Medicine
(Bethesda, Maryland) told an audience at the Food and Drug
Law Institute (Washington) annual meeting that personalized
See FDLI, page 5
OptiScan Biomedical initiates
enrollment for MANAGE study
By Omar Ford, Staff Writer
If successful, OptiScan Biomedical (Hayward, California)
could be the next David and Goliath story of med-tech. The small
firm has developed an automated bedside glucose monitoring
system designed to provide physicians with critical information
to manage patient glucose levels in the ICU.
If OptiScan gains approval for its OptiScanner 5000, the
company would be going head to head with devices from such
companies as Medtronic (Minneapolis) and Edwards Life
Sciences (Irvine, California).
“We’re truly the David and Goliath story, with a better mouse
trap, and the doctors care about the [OptiScanner 5000],” Peter
Rule, chairman/CEO of OptiScan, told Medical Device Daily.
See OptiScan, page 7
NEUROLOGY EXTRA
INSIDE
FDA POST-MARKET DRAFT HINTS AT
LENGTHIER POST-APPROVAL STUDIES
ESCALON TO DISTRIBUTE BICOM’S
TRANSPALPEBRAL TONOMETER
By Mark McCarty, Washington Editor
PAGE 2
PAGE 3
To subscribe, please call Medical Device Daily’s Sales Team at
(800) 477-6307; outside the U.S. and Canada, call (770) 810-3144.
Copyright © 2014 Thomson Reuters. Reproduction is strictly prohibited.
Visit our web site at www.medicaldevicedaily.com
Staff Writer Robert Kimball
on one of med-tech’s key sectors
Read this week’s Monday Special
MONDAY, APRIL 28 , 2014
MEDICAL DEVICE DAILY™ WASHINGTON ROUNDUP
FDA post-market draft hints at
lengthier post-approval studies
By Mark McCarty, Washington Editor
FDA’s device branch unveiled two draft guidances the week
of April 20, one of which is a draft guidance for determining
which types of data collection could be deferred until after a
device is approved. Among the conditions under which the
agency might defer some data collection efforts is when the
agency is concerned about a specific benefit-risk calculation, but
has a fairly clear picture of the overall benefit-risk profile offered
by the device. FDA gave two examples of extended follow-up in
the draft, including a post-approval study (PAS) for a corneal
lens required to accumulate 5,000 patient-years of experience,
a requirement that could endure beyond a device’s commercial
lifespan.
Perhaps the more conspicuous of the draft gudances FDA
released the week of April 20 addressed an expedited access
program for PMA devices, which the agency explained was
directed at PMAs designed to treat unaddressed needs and other
conditions seen by FDA as public health considerations (Medical
Device Daily, April 25, 2014). The language of the draft taking
up a “balancing of premarket and postmarket data collection”
made reference to the expedited access draft, and the data
collection draft may be seen as something of a companion piece
to the expedited access draft.
The data collection draft notes that the agency may go
along with a shift of data collection into the post-market setting
“under certain circumstances,” including when FDA is uncertain
as to specific benefits and risks pertaining to specific outcomes,
but when reviewers at the Office of Device Evaluation have “less
MEDICAL DEVICE DAILY
Medical Device Daily™ (ISSN# 1541-0617) is published every business day by
Thomson Reuters, 115 Perimeter Center Place, Suite 1100, Atlanta, GA 30346
PAGE 2 OF 8
uncertainty about the overall benefit-risk profile” at the time of
approval.
Uncommon or “minor risks” are candidates for a postmarket data collection effort, the draft observes, a statement
the agency applied as well to long-term benefits and risks.
The agency indicated it would be amenable to deferring some
types of data collection for “more mature technology” as well, a
concession the agency made thanks to the experience with prior
versions of a given device. FDA’s policy for advisory hearings has
generally reflected a belief that such hearings are necessary for
only the first three to four such applications.
The prospect of longer and larger PAS commitments
is consistent with comments heard at advisory committee
hearings. Panelists occasionally recommend a 10-year followup for PMA devices, a suggestion that often accompanies a
recommendation for a larger PAS cohort than device makers
may find practical. FDA’s Jeff Shuren, MD, director of the Center
for Devices and Radiological Health, indicated at the latest
annual meeting of the Food and Drug Law Institute (FDLI;
Washington) that he is unopposed to a pure registry study so
long as the electronic health record build-out is up to the task,
although some may find this an implausible proposition in the
near term for most devices.
FDA said that it reserves the right to withdraw the PMA if the
sponsor fails to live up to the PAS agreement, an action that it
has rarely if ever undertaken. Later, the draft acknowledges that
sponsors may encounter circumstances “outside of the sponsor’s
control” that render compliance with the PAS terms difficult or
impossible. The agency said it “intends to be reasonably flexible
about the timeframe” in such circumstances.
The draft remarks that a sponsor may make changes
to a product label “with the approval of FDA” that address
considerations such as an expansion or narrowing of indications
See Wshington, page 8
PRACTICAL INFORMATION
To subscribe, please contact our Sales Team at (800) 477-6307;
outside the U.S. and Canada, call 1-770-810-3144.
medicaldevicedaily.salessupport@thomsonreuters.com
U.S.A. Opinions expressed are not necessarily those of this publication.
For photocopy rights or reprints, please call Joe Rabus at
Mention of products or services does not constitute endorsement. All Rights
(770) 810-3121 or e-mail him at joseph.rabus@thomsonreuters.com.
Reserved. No part of this publication may be reproduced without the ­written
Send all press releases and related information to
­consent of Thomson Reuters (GST Registration Number R128870672).
medicaldevicedaily.newsdesk@medicaldevicedaily.com.
CONTACT US
medicaldevicedaily.newsdesk@medicaldevicedaily.com
BUSINESS OFFICE
Donald R. Johnston (Senior Director, Editorial), Sarah Cross (Marketing
Donald R. Johnston, (770) 810 3118 // Holland Johnson, (770) 810-3122 //
Director), Matt Hartzog, Paul Marino & Greg Rouse (Account
Amanda Pedersen, (912) 660-2282 // Omar Ford, (770) 810-3125 // Robert
Representatives)
Kimball, (770) 810-3127 // Mark McCarty, (703) 361-2519
ATLANTA NEWSROOM
Holland Johnson (Executive Editor), Robert Kimball (Senior Production Editor),
Mark McCarty (Washington Editor), Omar Ford & Amanda Pedersen (Staff Writers)
MONDAY, APRIL 28 , 2014
MEDICAL DEVICE DAILY™ AGREEMENTS/CONTRACTS
Escalon to distribute BiCOM’s
transpalpebral tonometer
Staff Report
Escalon Medical (Ardmore, Pennsylvania) has entered into
a distribution agreement with BiCOM (Long Beach, New York)
to distribute its transpalpebral Diaton tonometer. The Diaton
tonometer will be featured alongside the company’s new VuPad
ultrasound system at the Annual Symposium and Congress
of the American Society of Cataract and Refractive Surgery
(ASCRS) in Boston, April 25-29.
“We are excited to offer the Diaton tonometer as a
complementary product to our pachymetry ultrasound products,”
said CEO, Richard DePiano Jr. “Through our experienced sales
organization with reach into 90 countries, we are well positioned
to expand distribution of the Diaton tonometer, particularly into
Asia and Europe. Adding best-in-class ophthalmic product
solutions to our distribution network also demonstrates our
ongoing commitment to build on our position as a leader in
ophthalmic diagnostic instrumentation.”
The Diaton tonometer is a non-corneal contact tonometer used
through the eyelid to quickly and painlessly determine intraocular
pressure without directly touching the cornea or requiring use of
topical anesthesia. The Diaton tonometer is particularly useful in
cases where standard direct applanation tonometry is difficult or not
viable, such as with pediatric patients, in presence of certain corneal
pathology, following corneal surgery, and in cases of eye trauma.
In other agreements/contracts; Norgenix Pharmaceuticals
(Spartanburg, South Carolina) and CrossBay Medical (Howard
Beach, New York), reported a strategic alliance and revealed its
medical device co-promotion, the SonoSure Sonohysterography
and Endometrial Sampling Device.
Norgenix is partnering with CrossBay Medical for the copromotion of the SonoSure, a CE marked and 510(k) cleared
device indicated for use to access the uterine cavity for saline
infusion sonohysterography and to obtain an endometrial biopsy,
if indicated, utilizing the same device. Norgenix has exclusive
rights to market and distribute the SonoSure in the U.S., as well
as U.S. territories and military bases.
AUB occurs in 20% of women between the ages of 19 to
55. Saline Infusion Sonohysterography (SIS) and Endometrial
Biopsy (EMB) are routinely used in the workup for AUB. Many
providers perform these procedures at the same setting, using
separate instrumentation for each procedure. This requires
cannulation of the cervix at least twice. Other providers may
require patients to have separate visits for the procedures. The
Sonosure device combines Saline Infusion Sonohysterography
and Endometrial Biopsy in the same device. It is indicated for us
to access the uterine cavity for saline infusion sonohysterography
and to obtain an endometrial biopsy, if indicated, using the same
device. //
PAGE 3 OF 8
MDD Stock Watch
10 BIGGEST WINNERS FOR THE WEEK
By Percent
By Dollars
Thermogenesis
28.19
Zimmer Holdings
9.55
Zimmer Holdings
10.50
IDEXX Laboratories
5.81
Bovie Medical
10.46
Smith & Nephew plc 3.64
Cardiovascular
Systems
10.16
Cardiovascular
Systems
2.65
RTI Surgical
8.02
Mazor Robotics
1.00
Mazor Robotics
5.43
Zeltiq Aesthetics
0.85
Smith & Nephew
4.97
Johnson & Johnson
0.83
IDEXX Laboratories
4.93
Orthofix
International
0.49
Kips Bay Medical
4.84
The Cooper
Companies
0.44
Zeltiq Aesthetics
4.75
Thermogenesis
0.42
10 BIGGEST LOSERS FOR THE WEEK
By Percent
By Dollars
Quidel
-13.96
Intuitive Surgical
-45.62
Athenahealth
-12.21
Athenahealth
-17.77
Intuitive Surgical
-11.07
Thermo Fisher
Scientific
-5.01
Meridian Bioscience -9.49
Quest Diagnostics
-3.60
The Spectranetics
-9.12
Quidel
-3.40
Dehaier Medical
Systems
-8.16
Align Technology
-3.40
Imris
-8.15
Pall
-3.27
NxStage Medical
-6.52
C.R. Bard
-3.25
Align Technology
-6.37
Conmed
-2.28
Cynosure
-2.40
Cardiovascular
Systems
-0.49
MDD is on Twitter!
Stay Connected. Follow Us on Twitter!
www.twitter.com/meddevicesdaily
To subscribe call (800) 477-6307; outside the U.S. and Canada call (770) 810-3144 or email medicaldevicedaily.salessupport@thomsonreuters.com.
For customer service inquiries call (800) 336-4474; outside the U.S. and Canada call (215) 386-0100 or email medicaldevicedaily.support@thomsonreuters.com.
Copyright © 2014 Thomson Reuters. Reproduction is strictly prohibited. Visit our web site at www.medicaldevicedaily.com
MONDAY, APRIL 28 , 2014
MEDICAL DEVICE DAILY™ Roche
Continued from page 1
“What’s changed now is, instead of doing the Pap first and HPV
test second or the Pap and HPV together as recommended in
guidelines a couple years ago, now it’s turned around,” Mark
Stoler, MD, a professor (emeritus) of pathology and clinical
gynecology at the University of Virginia Health System
(Charlottesville), told Medical Device Daily.
With this approval, the cobas HPV test can be done first and
then only in certain situations the Pap test can be done also,
Stoler explained. “Doing the HPV test first might seem like a
radical idea,” he said, but the data very clearly supports this as a
safe and more effective strategy.
The FDA approval offers women a “better alternative
method to reassure themselves they do not have this deadly, yet
preventable disease,” Stoler said. “Using the cobas HPV test as
a primary screen means that women will have the opportunity
to receive a better and more accurate standard of care. Clinically
validated HPV screening detects the virus that causes cervical
cancer and dose a better job identifying women at risk than Pap
testing alone. But most importantly, women found to be HPV
negative are provided a greater sense of security that they are
safe from the disease.
Roche said its cobas HPV test provides both pooled high-risk
HPV DNA results and individual detection of HPV 16 and HPV
18, the two types responsible for about 70% of cervical cancer.
The FDA’s decision to approve the expanded use for the cobas
HPV test was based on results from the landmark ATHENA trial,
which enrolled more than 47,000 women, the company noted.
The study demonstrated that one in four women who are HPV
16 positive will have cervical disease within three years and that
nearly one in seven women with normal Pap cytology who were
HPV 16 positive actually had high-grade cervical disease that
was missed by cytology.
In addition, results from the ATHENA trial included a
comparison of a cobas HPV test screening strategy to alternative
strategies using Pap cytology and HPV testing. The comparison
showed that a strategy leveraging the ability of the cobas HPV
test to identify women testing positive for HPV 16 or 18, and using
cervical cytology (Pap) as a triage, follow-up test, would allow
clinicians to detect more disease without referring a significant
number of women to unnecessary follow-up.
It may have surprised to some that the FDA approval came
so quickly after the FDA panel recommendation. But, as Stoler
said, “they had a very high quality of data set” and that data is
very convincing.
But clinicians and patients shouldn’t take this approval as
Roche or FDA taking the PAP away. “Nobody is saying don’t do
two tests,” Stoler said. “The strategy for using this test is that it
still has the Pap in it for the people who need it.”
Stoler emphasized that “nobody would recommend this,
nobody would approve it, if it wasn’t safe, effective and supported
PAGE 4 OF 8
[by strong data].”
While some clinicians and patients may ask why they
shouldn’t just do the HPV and Pap tests together. The answer,
according to Stoler, is that doing so wouldn’t add any value. “It
simplifies screening, we get the same information doing one test
that we previously got with two tests,” Stoler said.
Roche said the cobas is the only FDA-approved HPV assay
that provides specific genotyping information for HPV 16 and
18, the highest-risk types, while simultaneously reporting the 12
other high-risk HPV types as a pooled result, all in one run, from
one patient sample.
The test previously received FDA approval in April 2011 for
screening patients age 21 and older with abnormal cervical
cytology results and for use adjunctively with normal cervical
cytology in women ages 30 and over to assess the presence
or absence of high-risk HPV genotypes. Roche submitted a
premarket approval supplement for the cervical cancer primary
screening indication in June 2013.
The test is performed on the cobas 4800 system, which
offers walk-away automation of nucleic acid purification,
PCR (polymerase chain reaction) set-up and real-time PCR
amplification and detection to help laboratories achieve
maximum efficiency. The system also runs the cobas CT/NG test
(chlamydia/gonorrhea), the cobas BRAF V600 mutation test
and the cobas EGFR mutation test.
“We are very pleased that the FDA has approved this test for
first-line use in cervical cancer screening. It is a recognition for
the value the cobas HPV test provides to physicians and women
to make more informed decisions that can ultimately prevent
cervical cancer development,” said Roland Diggelmann, COO
Division Roche Diagnostics. “This is an outstanding example of
how innovation in diagnostics is shifting the disease management
paradigm to improve patient care and people’s health. We
are committed to working with the medical community and
professional organizations to put the necessary clinical practice
guidelines in place to encourage providers to incorporate this
new screening strategy alternative in their patient protocols.” //
Advertise Here
...and reach high-level med-tech
professionals every day!
For advertising opportunities in
Medical Device Daily, please contact
Joe Rabus at (770) 810-3121 or
joseph.rabus@thomsonreuters.com
To subscribe call (800) 477-6307; outside the U.S. and Canada call (770) 810-3144 or email medicaldevicedaily.salessupport@thomsonreuters.com.
For customer service inquiries call (800) 336-4474; outside the U.S. and Canada call (215) 386-0100 or email medicaldevicedaily.support@thomsonreuters.com.
Copyright © 2014 Thomson Reuters. Reproduction is strictly prohibited. Visit our web site at www.medicaldevicedaily.com
MONDAY, APRIL 28 , 2014
MEDICAL DEVICE DAILY™ FDLI
Continued from page 1
medicine is still the future of medicine, but that she sees “a
disturbing trend” of ebbing interest on the part of industry, a
trend she said is fueled in part by payer skepticism.
Becker reminded attendees that FDA “is strongly invested
in policy, infrastructure and science to promote the success” of
personalized medicine, and she remarked that a conspicuous
share of companion Dx applications are designed to deal with
orphan drugs. Becker also pointed to the strategic advantage
of a well-defined set of biomarkers for patient selection and
titration, remarking that all of pharma “is including the use of
biomarkers in the drug development” process at some point.
“Even if you don’t end up with a companion Dx,” she observed,
having a set of biomarkers “can make a huge difference in
informing the decision” of whether to take a stage II drug trial
to stage III.
Despite these considerable attractions, Becker said, “one
thing that strikes me at the moment is that companion Dx,
while clearly important,” is losing its luster for pharma. She said
“interest in industry is waning,” a phenomenon she hinted is not
a blip on the commercial radar screen. She said this ebbing of
interest is “a disturbing trend,” and – perhaps predictably – is
“driven by financial forces.”
Still, Becker said revenues from precision medicine
are expected to grow. She pointed out that companion Dx
partnerships roughly doubled from a dozen in 2004 to 20-plus
in 2010, but added, “the question that is being asked more
frequently is: ‘Do we need to move ahead with the companion
diagnostic?’”
FDA’s draft guidance for companion diagnostics hinted
at hostility to the notion of approving a drug packaged with a
companion diagnostic should the application for the diagnostic
fail, but Becker indicated FDA is not entirely averse to approving
a drug application that relies on a biomarker even if the test
does not meet the agency’s expectations. She stated further that
while payers are skeptical, “there are other ways to develop and
market these tests.” Becker observed that some drug companies
are “entirely opting out of the FDA process” and going with labdeveloped tests (LDTs) to handle the diagnostic piece of the
puzzle.
Becker made note of what she described as “pain points”
for companies in the diagnostic space, including unfamiliarity
with the PMA process. Compared to a 510(k), a PMA “is a large
challenge,” she said, but she cited further the costs associated
with “the risk of failure in phase III for the companion Dx.”
Even when coverage is available, reimbursement “is
unclear or unfavorable for many of these products,” Becker
said, adding that LDTs “are in effect direct competitors for
these products.” She also reminded that there are no R&D tax
credits for companion Dx products, unlike the orphan drugs
PAGE 5 OF 8
with which they are often paired, adding that there is also no
program office at FDA, no waiver of FDA user fees, and no
exclusivity for the companion Dx, leaving the orphan drug in
the position of being an orphan again should the companion
diagnostic not clear its regulatory or coverage/reimbursement
hurdles.
Becker countered the deluge of dismaying news by
remarking, “most drugs are ineffective in a general population,”
and she reminded that precision medicine can reduce
development times and costs as well as the rate of adverse
events associated with the therapeutic. She suggested that
policymakers examine ideas such as financial incentives for
diagnostics for orphan drugs and allowing a companion Dx to be
used in more than one application, moves she said might help
“to stem the waning interest.”
HALL SEES OPENING IN OFF-LABEL PROHIBITION
Device makers interested in leveraging their investments
have watched as FDA has attempted to corral their promotions
for off-label uses, but a well-known attorney believes he sees
another angle by which industry might exercise more First
Amendment leverage in off-label discussions. Ralph Hall of
the University of Minnesota School of Law (Minneapolis), told
an FDLI audience that one of the parties in the case of Ony v.
Cornerstone used coverage in the peer-reviewed literature to
fend off a lawsuit, and that the success of this defense suggests
an opening in the FDA armor where off-label discussions are
concerned.
Hall referenced a number of other cases in his remarks,
including Caronia, which many observers believed was
predicated by too unusual a set of conditions to be useful
in prying open some room for off-label discussions. He
explained that Cornerstone Therapeutics (Cary, North
Carolina) and Ony (Amherst, New York) are competitors
in the area of therapies for respiratory distress syndrome
in neonates, and that the results of a head-to-head study
suggested that Cornerstone’s offering was associated with
fewer deaths and better outcomes. Hall quipped, “there was
a little controversy over that,” which found its way to the
U.S. Court of Appeals for the Second Circuit. The Court ruled
on the case in June 2013.
Hall continued: “Cornerstone goes out and uses this study
to promote their product,” but “Ony isn’t happy” and complains
about the study, alleging among other things that the data for
length of stay were among those “deliberately omitted” from the
article in the Journal of Perinatology.
“Cornerstone’s defense is a First Amendment defense,”
Hall said, but Ony also sued physicians in the study as well as
the publisher of the journal. The publisher likewise argued the
First Amendment, however, and Cornerstone asserted it had
“accurately disseminated scientific information,” Hall said. The
district court agreed, and Ony appealed.
The Court of Appeals, Hall continued, said the First
See FDLI, page 6
To subscribe call (800) 477-6307; outside the U.S. and Canada call (770) 810-3144 or email medicaldevicedaily.salessupport@thomsonreuters.com.
For customer service inquiries call (800) 336-4474; outside the U.S. and Canada call (215) 386-0100 or email medicaldevicedaily.support@thomsonreuters.com.
Copyright © 2014 Thomson Reuters. Reproduction is strictly prohibited. Visit our web site at www.medicaldevicedaily.com
MONDAY, APRIL 28 , 2014
MEDICAL DEVICE DAILY™ Neural
Continued from page 1
(Gaithersburg, Maryland), and Oncosec Medical (San Diego) use
electroporation to deliver DNA, for vaccination or therapeutic
purposes.
And electrical current is also used for another, heretofore
separate purpose in medicine, namely, in neural prostheses
that use direct electrical stimulation to communicate directly
with the brain, which uses electrical impulses as its information
processing currency.
Cochlear implants, which replace the cells in the middle ear
that sense sound and can restore hearing to profoundly deaf
individuals, were the first such neuroprosthesis to make it into
routine clinical use.
That they work at all seems, at first glance (or whisper),
rather fantastic – the first cochlear implant replaced roughly
10,000 outer hair cells with a single electrode. Modern devices
have between one and two dozen such electrodes.
Cochlear implants might work even better, however, if
they were able to make better contact with the auditory nerve
cells they are supposed to stimulate. And since the position
of the electrodes is limited by the anatomy of the cochlea,
the alternative is to coax the neurons to grow towards the
electrodes.
Neurons will grow towards certain signaling factors,
among them brain-derived neurotrophic factor (BDNF). So
the researchers reasoned that if they could get cells near the
electrodes to express BDNF, it might serve as a beacon for
auditory nerve cells to send outgrowths towards those cells.
“The cochlear neurons express receptors for the BDNF
that we have made the cells close to the electrodes express,”
corresponding author Gary Housley of the University of New
South Wales told Medical Device Daily’s sister publication
BioWorld Today. “The BDNF acts as a nerve growth factor and
the surviving neurons . . . [follow] the concentration gradient of
the BDNF – which is towards the cochlear implant electrodes.”
In their experiments, which were performed in guinea pigs,
the authors used the cochlear implants to deliver pulses of
electroporating current during the implantation procedure. That
current enabled nearby cells to take up DNA plasmids containing
BDNF, as well as a fluorescent marker. The cells expressed those
genes for a few weeks – long enough to coax auditory nerve cells
to send outgrowths in their direction.
The team plans, among other things, to see whether they can
get gene expression to last longer than a few weeks by tweaking
their procedure, though Housley noted that from other studies,
there is grounds for optimism that once the nerve fibers have
regenerated, the active electrical stimulation by the cochlear
implant in operation will be sufficient to make them remain in
touch with the electrodes.
Housley and his team then tested whether those outgrowths
PAGE 6 OF 8
made it easier to stimulate the auditory nerve, and found that the
threshold of electrical current they needed to get the auditory
nerve’s attention was lower in treated animals. Electrical
recordings suggested that they were able to transmit a greater
range of signals in treated animals, which could in principle
translate into a better transmission of complex sounds.
The scientists hope that specifically for cochlear implants,
the approach – which they next plan to validate in a clinical trial
– will help improve pitch perception.
But the work also provides proof of principle that brain
stimulation and gene therapy could be a more general package
deal.
Deep brain stimulation is an approved treatment for tremor,
Parkinson’s disease, and dystonia. And it is being tested in other
indications including depression.
“The directed gene delivery by close-field electroporation
has advantages in that it can support a wide range of therapeutic
gene cassettes – far greater with regard to size and hence
design than viral packaging [for example],” Housley said. “So
neurological applications can be tailored to enable a range of
existing viral-based approaches that are not currently tenable
due to safety constraints and issues of spread.” //
FDLI
Continued from page 5
Amendment covers statements of opinion, and some of the
assertions found in medical journals are expressions of opinion.
Hall said the Court had remarked more or less to the effect that
the conclusions of empirical research are subject to revision, a
fact that does not dilute First Amendment effects.
“The Court was very clear that the authors disclosed”
several caveats, Hall commented, and the Court also
expressed the view that jurists for the most part “do not
referee scientific debates.” The Court further took the position
that readers of scientific journals are presumed to be fairly
savvy, and thus invoked a three-part test. The test asks;
whether the data are fraudulent, whether the article provides
an accurate description of data (and methodologies), and
whether the matter at hand is the subject of an ongoing
scientific debate. “Because Cornerstone accurately
described the article . . . there’s no liability,” Hall shrugged.
“I kept waiting for the Central Hudson discussion,” Hall
said, which would pose the question of “how does this case
apply to government action” where off-label discussions
are concerned. He noted that the key difference in Ony is
that it argues that scientific speech is protected. This might
lead a device firm to consider the possibility that “because
the scientific article is protected, I can use that” to justify
expanded off-label discussions with physicians.
This, Hall said, is “an opening people can think about in
arguing the off-label” point. //
To subscribe call (800) 477-6307; outside the U.S. and Canada call (770) 810-3144 or email medicaldevicedaily.salessupport@thomsonreuters.com.
For customer service inquiries call (800) 336-4474; outside the U.S. and Canada call (215) 386-0100 or email medicaldevicedaily.support@thomsonreuters.com.
Copyright © 2014 Thomson Reuters. Reproduction is strictly prohibited. Visit our web site at www.medicaldevicedaily.com
MONDAY, APRIL 28 , 2014
MEDICAL DEVICE DAILY™ OptiScan
Continued from page 1
OptiScan is making some important steps in its bid to
gain FDA approval as it has already enrolled the first patient
in MANAGE, a pivotal, multi-center investigational device
exemption (IDE) clinical study of the OptiScanner 5000. The
study is expected to enroll 200 patients at up to 10 sites,
most of which will be located in the U.S. The initial three
clinical sites are Washington University School of Medicine
(St. Louis); Tufts University School of Medicine (Boston);
Saint Luke’s Mid-America Heart Institute (Kansas City,
Missouri).
The OptiScanner 5000 automates the measurement
of patients’ plasma glucose, as opposed to current manual
measurement of glucose in whole blood. It is estimated that
about 20% of ICU patients have pre-existing diabetes and
an additional 40% to 60% of ICU patients suffer from “stress
hyperglycemia” or a temporary elevation of glucose levels, with
all of these patients requiring accurate glucose monitoring to
maintain glycemic control.
“The device is the accumulation of about eight years of
work,” he said. “It is modeled after best practices of measuring
glucose worldwide.”
This pivotal MANAGE IDE study follows OptiScan’s
previously completed MANAGE I and MANAGE II trials,
which were conducted at two European research centers
and evaluated the OptiScanner 5000 in very sick ICU
patients. Taken together, these studies represent the most
comprehensive clinical validation program conducted to
date with a continuous blood monitoring platform in the
critical care setting. According to the company, results from
these studies demonstrated the ability of the OptiScanner
5000 to combine accurate blood glucose measurement
with the convenience of continuous, real-time bedside
monitoring.
Rule said the device could be regulated as a PMA.
“The size of the trial and the complexity of the trial with prenegotiated endpoints is a PMA-quality trial,” he said. “Whether
or not FDA decides to regulate us as a 510(k) or a PMA is [the
agency’s decision]. I assure you this trial has the same flavor to it
as a PMA trial and in fact there’s probably no difference.”
The technology already has approval in Europe, the company
noted.
“We, as of this year, have launched in Italy,” Rule said.
“Prior to that we did have the CE mark, but we felt as if
we wanted more clinical research and we went to two in
particular ground-breaking centers, one in Amsterdam
and one in Brussels. We conducted a study on about 175
patients that were also ICU patients and very critically ill.
We made sure that we had fully covered on an ethical basis
the intended use of the product and these data are what
PAGE 7 OF 8
we submitted to the FDA. We never had safety issues in
the application in the use of our product, so FDA was very
forthcoming and a very good partner in helping with the
design of this trial.”
OptiScan said it is hoping for FDA approval sometime next
year.
“That puts the submission very early in the first quarter
of 2015,” he said. “We would expect approval very early in
the second quarter. Whether FDA would follow that timeline
is of course in their hands. We’ve been working with them
for a good period of time, we’ve tried to provide them the
scientific data that they need and we are hopeful that as
a result of that they will need to approve this product on a
timely basis.” //
FINANCINGS ROUNDUP
Lombard to offer 5 million
shares at $11/per in IPO
Staff Report
Lombard Medical (Irvine, California) reported the pricing of
the initial public offering of 5,000,000 ordinary shares at a price
to the public of $11 per share. The shares will be listed on the
Nasdaq Global Market under the ticker symbol “EVAR” on April
25. In addition, Lombard Medical has granted the underwriters a
30-day option to purchase up to an additional 750,000 ordinary
shares from Lombard Medical.
In advance of Lombard Medical’s shares commencing
trading on the Nasdaq Global Market, trading in the shares of
Lombard Medical Technologies PLC on the AIM market of the
London Stock Exchange will be suspended and trading in the
shares will be cancelled.
Jefferies and Barclays Capital are acting as joint bookrunning managers for the proposed offering, and BTIG is acting
as co-manager.
A registration statement relating to these securities has
been filed with, and declared effective by, the Securities and
Exchange Commission. //
PEOPLE IN PLACES
•Orthofix International (Lewisville, Texas) has named
James Hinrichs to its board. Hinrichs was the CFO of CareFusion
since 2010. Orthofix International makes reconstructive and
regenerative orthopedic and spine solutions.
• Osiris Therapeutics (Columbia, Maryland) has named
Dwayne Montgomery as GM, orthopedics and sports medicine,
reporting to Lode Debrabandere, PhD, president/CEO. Most
recently, Montgomery was the senior VP of sales and marketing
for IlluminOss Medical. Osiris is a stem cell company focused on
developing and marketing products to treat conditions in wound
care, orthopedic and sports medicine markets.
To subscribe call (800) 477-6307; outside the U.S. and Canada call (770) 810-3144 or email medicaldevicedaily.salessupport@thomsonreuters.com.
For customer service inquiries call (800) 336-4474; outside the U.S. and Canada call (215) 386-0100 or email medicaldevicedaily.support@thomsonreuters.com.
Copyright © 2014 Thomson Reuters. Reproduction is strictly prohibited. Visit our web site at www.medicaldevicedaily.com
MONDAY, APRIL 28 , 2014
MEDICAL DEVICE DAILY™ Washington
Continued from page 2
for use. However, the agency indicated that such changes could
trigger a requirement for a PMA supplement, which can in turn
trigger a need for an advisory hearing. The draft indicated also
that a panel hearing may be in order to address circumstances
in which “the results of the study may be difficult to interpret.”
The accompanying Federal Register notice of April 22
says that those who wish to comment on the draft may do so
through July 22 at regulations.gov under docket number FDA2014-D-0090.
GE seeks cover of MMA for T-wave test
Diagnostic technologies abound, making it difficult for
government agencies to keep up, and a division of GE Healthcare
(Wauwatosa, Wisconsin) is trying to prod the Centers for
Medicare & Medicaid Services to keep up with electrophysiology
testing standards. The company requested in a March 20 letter
that CMS cover testing for microvolt T-wave alternans with the
modified moving average (MMA) signal processing approach, a
standard backed by at least one medical society.
Scott Burke, director of ambulatory ECG for GE, remarked
that FDA cleared the MMA under K032513, a 510(k) application
the agency approved in 2003. Burke indicates that the hazard
ratios for prediction of sudden cardiac arrest by the Spectral
method and MMA “are similar” within specific populations and
overall. He asserted further that the body of evidence behind
the MMA “is significantly more robust than when Medicare last
considered this issue in 2008.”
Burke cited an article appearing in the Journal of the
American College of Cardiology in 2011, an article Burke said
reflected the view that the algorithms “are comparable.” CMS
decreed in its May 12, 2008, coverage memo that microvolt
T-wave alternans testing “is non-covered . . . if measurement
is not performed employing the spectral analysis method.” The
agency noted also that the Heart Rhythm Society (Washington)
had filed a letter during the initial comment period for the 2008
coverage analysis “that did not support coverage” of the MMA
method.
CMS indicated that the open comment period runs through
May 23, to be followed by a coverage proposal on or before Oct.
23. The agency said it would publish a final decision memo Jan.
12, 2015.
CMS still working on ICD-10
The bill that rendered another doc fix also delayed
implementation of ICD-10, but the Centers for Medicare &
Medicaid Services intends to nudge the conversion program
along all the same. According to an April 23 story at ICD10monitor.
com, officials at CMS were unprepared for the congressionally
mandated delay, but are nonetheless undeterred.
PAGE 8 OF 8
The Advanced Medical Technology Association (AdvaMed;
Washington) remarked in a March 27 statement that the delay
to ICD-10 – which providers will not have to comply with until
October 2015 – will delay the introduction of new codes needed
to keep pace “with changes in medical practice and healthcare
delivery.” //
PRODUCT BRIEFS
• Natera (San Carlos, California) has received a new
conditional approval from the New York State Department of
Health to offer its Panorama non-invasive prenatal test (NIPT)
for aneuploidies and 22q11.2 deletion syndrome in all pregnant
women. The Panorama test is a screening tool that uses a blood
sample to assess the risk of certain chromosomal conditions that
may affect a baby’s health. Panorama can safely and accurately
screen for many genetic conditions, including Down syndrome,
Edwards Syndrome and Patau syndrome, and as of March 2014,
it was expanded to screen for five microdeletions. Microdeletions
are tiny missing pieces of DNA at the sub-chromosomal level,
which can have serious health implications depending on the
location of the deletion.
22q11.2 deletion syndrome (also known as DiGeorge
syndrome or “22q”) is the most common microdeletion on
Panorama’s screening panel, affecting around 1 out of every
2,000 births regardless of maternal age at time of pregnancy.
The syndrome can cause heart defects, growth delays, immune
system and endocrine issues, developmental and speech
delays, and behavioral, emotional and psychiatric challenges.
There is no cure for 22q, though early identification and medical
intervention helps to address associated symptoms.
• Volcano (San Diego) reported the commencement of
a limited market release of its FDA cleared and CE marked
technology SyncVision, with cases being performed in the U.S.
and Europe. Volcano’s SyncVision technology system is an online image processing workstation for coronary catheterizations
that allows the physician to navigate simultaneously on
angiogram and an IVUS image in a single correlated view using
co-registration of the Eagle Eye Platinum catheter with X-ray
angiography. SyncVision is designed to bring the detailed vessel,
lumen and wall structure from angiography and the spatial
localization of Volcano’s intravascular ultrasound images within
the coronary tree together in a co-registered view to facilitate
more informed treatment decisions and more efficient, enhanced
workflow performance.
Follow MDD on Twitter to keep on top of the
latest med-tech updates!
www.twitter.com/meddevicesdaily
To subscribe call (800) 477-6307; outside the U.S. and Canada call (770) 810-3144 or email medicaldevicedaily.salessupport@thomsonreuters.com.
For customer service inquiries call (800) 336-4474; outside the U.S. and Canada call (215) 386-0100 or email medicaldevicedaily.support@thomsonreuters.com.
Copyright © 2014 Thomson Reuters. Reproduction is strictly prohibited. Visit our web site at www.medicaldevicedaily.com
NEUROLOGY EXTRA
Keeping you up to date on recent developments in neurology
By Robert Kimball, Staff Writer
Atypical brain connectivity associated with
autism spectrum disorder
Autism spectrum disorder (ASD) in adolescents appears to
be associated with atypical connectivity in the brain involving
the systems that help people infer what others are thinking
and understand the meaning of others’ actions and emotions.
The ability to navigate and thrive in complex social systems is
commonly impaired in ASD, a neurodevelopmental disorder
affecting as many as 1 in 88 children.
The authors used functional magnetic resonance imaging
to investigate connectivity in 2 brain networks involved in
social processing: theory of mind (ToM, otherwise known as the
mentalizing system, which allows an individual to infer what
others are thinking, their beliefs, their intentions) and the mirror
neuron system (MNS, which allows people to understand the
meanings and actions of others by simulating and replicating
them). The study included 25 adolescents with ASD (between
the ages of 11 and 18) and 25 typically developing adolescents.
Compared to typically developing adolescents, those with
ASD showed both over- and under-connectivity in the ToM
network, which was associated with greater social impairment.
The adolescents with ASD also had increased connectivity
between the regions of the MNS and ToM, suggesting that ToMMNS “cross talk” might be associated with social impairment.
“This excess ToM-MNS connectivity may reflect immature or
aberrant developmental processes in 2 brain networks involved
in understanding of others, a domain impairment in ASD.
Further, robust links with sociocommunicative symptoms of
ASD implicate atypically increased ToM-MNS connectivity in
social deficits observed in ASD.”
A separate report estimated the change in prevalence
of parent-reported ASD from 2007 to 2011-2012 and is based
on newly released data from the 2011-2012 National Survey of
Children’s Health (NSCH), part of a telephone survey conducted
by the U.S. Centers for Disease Control and Prevention (CDC).
Estimates are presented for the prevalence and severity of
parent-reported ASD diagnoses for school-aged children (those
aged 6-17 years).
A total of 91,642 NSCH 2007 interviews were completed
from April 2007 through July 2008. A total of 95,677 NSCH 20112012 interviews were completed from February 2011 through
June 2012. The overall response rate for 2011-2012 (23.0%)
was lower than the rate for 2007 (46.7%) primarily due to the
inclusion of cell-phone interviews in 2011-2012. Information
about parent-reported ASD diagnosis was obtained for 63,967
children aged 6-17 in 2007 and for 65,556 in 2011-2012. The
cohort analyses include information about parent-reported ASD
diagnosis for 56,399 children aged 2-13 in 2007.
MONDAY, APRIL 28 , 2014
For 2007 versus 2011-2012, the percentage of children
with parent-reported ASD was reported as follows: ages 6-17
years, 1.16% vs 2.00% (boys, 1.80% vs 3.23%; girls, 0.49% vs
0.70%); ages 6-9 years, 1.31% vs 1.82%; ages 10-13 years, 1.45%
vs 2.39%; ages 14-17 years, 0.73% vs 1.78%. Based on parent
reports, the prevalence of diagnosed ASD in 2011-2012 was
estimated to be 2.00% for children aged 6-17. This prevalence
estimate (1 in 50) is significantly higher than the estimate (1.16%,
or 1 in 86) for children in that age group in 2007. Statistically
significant increases in the prevalence of parent-reported ASD
were observed for all age groups.
Between 2007 and 2011-2012, the prevalence estimate for
parent-reported ASD diagnoses among U.S. children aged 6-17
increased significantly, from 1.16% to 2.00%. Increases in the
prevalence of parent-reported ASD continued through 20112012, and much of the recent increase (especially for children
aged 6-13) was the result of diagnoses of children with previously
unrecognized ASD (see Article Review: “Changes in Prevalence
of Parent-Reported Autism Spectrum Disorder in School-Aged
U.S. Children: 2007 to 2011-2012.” National Health Statistics
Reports, as cited in the Incidence and Prevalence Database).
Breakthrough: scientists use ear implants
to regrow auditory nerves
For the first time, scientists have used a cochlear implant to
deliver gene therapy, allowing regrowth of auditory nerves. As
well as improving hearing for those with the ear implants, the
technique holds the potential to treat an array of neurological
and psychiatric disorders, according to the investigators.
The research team, from the University of New South
Wales (UNSW) in Australia, recently published the details of
their breakthrough method in the journal Science Translational
Medicine. The researchers say it is well known that if
neurotrophins – naturally occurring proteins important for
neuron development, function and survival –are delivered
to the cochlea of the ear, auditory nerve endings are able to
regenerate. However, carrying out such a technique has proven
difficult for scientists. The team said that it has not been possible
to localize delivery of neurotrophins to the cochlea safely using
drug delivery or viral-based gene therapy. With this in mind, they
looked at whether cochlear implants could be used for gene
therapy.
Any sounds that these pick up are changed into electrical
signals that are sent to the electrodes, which stimulate the
auditory nerves and send signals to the brain. These signals are
perceived as sound. In their study, the researchers were able to
use electrical pulses delivered from the cochlear implants to
send a DNA solution to cells close to the implanted electrodes.
Continues on next page
MEDICAL DEVICE DAILY™ EXTRA
PAGE 1 OF 2
NEUROLOGY EXTRA
Continued from previous page
These cells were then able to produce neurotrophins, therefore
triggering regeneration of auditory nerves. Jim Patrick, chief
scientist and senior vice president of Cochlear Limited, who
helped fund the study, says the team’s discovery has important
implications for the future of cochlear implants and the 324,000
people worldwide who have received them so far.
Penn Medicine researchers uncover
mechanism behind anesthetic action
Despite decades of common use for surgeries of all kinds,
the precise mechanism through which general anesthesia works
on the body remains a mystery. This may come as a surprise
to the millions of Americans who receive inhaled general
anesthesia each year. New research led by the Perelman School
of Medicine at the University of Pennsylvania (Philadelphia)
investigated the common anesthetic sevoflurane and found that
it binds at multiple key cell membrane protein locations that
may contribute to the induction of the anesthetic response. Their
findings will appear online in PNAS.
This paper represents the team’s most recent findings.
Researchers found that sevoflurane’s interaction with
sodium channels plays an essential role in the generation
of the electrical impulses necessary for the communication
between nerve cells in the brain. “We sought to understand
the molecular basis of the interaction of sevoflurane with the
sodium channel as a starting point to determine how similar
anesthetics might elicit the anesthetic response,” said the
study’s lead author, Annika Barber, PhD, a post-doctoral
researcher in the department of Neuroscience at the Perelman
School of Medicine at the University of Pennsylvania. At the
time the research was conducted, she was a doctoral candidate
at Thomas Jefferson University (Philadelphia). In concert with
the Institute for Computational Molecular Science of Temple
University (Philadelphia), Barber first used molecular dynamic
simulation, a 3-D computer modeling method, to visualize
possible interactions of sevoflurane with discrete parts of the
bacterial sodium channel called NaChBac.
This archetypal membrane protein is homologous to
sodium channels found in human brain. “Given the physical and
chemical properties of inhaled anesthetics, we expected binding
to many possible sites; simulation, however, helped us limit and
identify the sites where the binding of sevoflurane might actually
change the function of the sodium channel,” said Barber.
The team found three key binding sites possibly linked to the
anesthetic response. The first involves the channel’s sodium pore
itself, which is plugged by sevoflurane; the second concerns the
gate that governs opening and closing of the sodium channel in
response to a voltage change across the membrane of a neuron;
and the third surrounds a second gate that controls sodium
flow by changing the shape of the channel’s narrow pore. These
MONDAY, APRIL 28 , 2014
three sites, researchers hypothesize, work together to turn off
firing of electrical impulses in key neurons and thus, induce the
anesthetic state.
Oops! Researchers find neural
signature for mistake correction
Culminating an eight-year-search, scientists at the
RIKEN-MIT Center for Neural Circuit Genetics (Cambridge,
Massachusetts) captured an elusive brain signal underlying
memory transfer and, in doing so, pinpointed the first neural circuit
for “oops” ? the precise moment when one becomes consciously
aware of a self-made mistake and takes corrective action.
The findings, published in Cell, verified a 20-year old
hypothesis on how brain areas communicate. In recent years,
researchers have been pursuing a class of ephemeral brain
signals called gamma oscillations, millisecond scale bursts
of synchronized wave-like electrical activity that pass through
brain tissue like ripples on a pond. In 1993, German scientist
Wolf Singer proposed that gamma waves enable binding of
memory associations.
For example, in a process called working memory, animals
store and recall short-term memory associations when exploring
the environment. In 2006, the MIT team under the direction of
Nobel Laureate Susumu Tonegawa began a study to understand
working memory in mice. They trained animals to navigate
a T maze and turn left or right at a junction for an associated
food reward. They found that working memory required
communication between two brain areas, the hippocampus and
entorhinal cortex, but how mice knew the correct direction and
the neural signal for memory transfer of this event remained
unclear. The study’s lead author Jun Yamamoto noticed that
mice sometimes made mistakes, turning in the wrong direction
then pausing, and turning around to go in the correct direction,
trials he termed “oops” in his lab notebook.
Intrigued, he recorded neural activity in the circuit and
observed a burst of gamma waves just before the “oops” moment.
He also saw gamma waves when mice chose the correct direction,
but not when they failed to choose the correct direction or did not
correct their mistakes. The critical experiment was to block gamma
oscillations and prevent mice from making correct decisions.
To do this, the researchers created a transgenic mouse
with a light-activated protein called archaerhodopsin (ArchT) in
the hippocampus. Using an optic fiber implanted in the brain,
light was flashed into the hippocampal-entorhinal circuit,
shutting off gamma activity. In accord, the mice could no longer
accurately choose the right direction and the number of “oops”
events decreased. The findings provide strong evidence of a
role for gamma oscillations in cognition, and raise the prospect
of their involvement in other behaviors requiring retrieval and
evaluation of working memory.
MEDICAL DEVICE DAILY™ EXTRA
PAGE 2 OF 2