Pharmaceutical Commerce - September/October 2017 - 9

Top News
EMA entertains relocation bids,
readies a business-continuity plan
New location, following Brexit, will be decided in November
One of the first realizations following
the Brexit vote in the UK last year was that
the European Medicines Agency (EMA),
which recently had centralized its operations
in London, England, would need to leave-
and leave quickly. Since then, the agency has
readied a relocation plan, and on August 1,
announced that 19 cities within the EU had
submitted bids to be the new home. (The
list of cities is literally A to Z: Amsterdam
to Zagreb.) The bids are to be evaluated
by a working group of the European
Commission, with recommendations
forwarded to the European Council (made

up of the heads of state of the EU) for a
final decision in November. The intent is
to have EMA settled in a place by March
2019, which is the official deadline for the
UK's exit.
Priority plan
In terms of physical movement, EMA
is a relatively small agency, with a staff of
around 900 (FDA, by comparison, has
15,000-not all of whom are at the White
Oak, MD headquarters). EMA is set up to
coordinate activities of the health agencies
of its member states; there are some 4,500

experts on call, for example, to assist in
drug evaluations. To ensure business
continuity, EMA has published a threelevel priority plan, with drug reviews and
patient safety issues as the top priority, for
which operations will be "business as usual"
during the transition; likewise for secondtier priorities, such as publications. A third
level, including a variety of IT and data
standardization efforts, is temporarily on
hold.
The siting of EMA is an economic plum
regardless of its staff size, notes Rory Mullen,
VP for Biopharma and Food at IDA Ireland

(the country's economic development
authority). The coordinating nature of its
operations means a high number of visits
to the headquarters, a boon for travel
and lodging. Dublin, Ireland's bid for the
new location has the advantages of being
in a country with a high concentration of
biopharma activity today; in addition, he
points out, Ireland will be the only Englishdominant-speaking nation within the
EU after Brexit, which could be a factor
for streamlining coordination between
EMA and other global agencies including,
obviously, FDA.

Post-approval trials of new drugs are showing limited clinical value
Is the accelerated-approval process providing a net benefit to patients?
It's a classic case of asking whether
the glass is half-full or half-empty: of 22
oncology drugs for 24 indications that were
granted accelerated approval between 2009
and 2013, and with at least three years of
follow-on study completion, post-approval
requirements were completed for 10
of the 24 indications and demonstrated
efficacy. Of the 14 indications not yet
completed, there were delays, failed results
or terminations; seven of the 14 were still
progressing. And of those 14 indications,
clinical benefit had not yet been confirmed
for eight indications that had been approved
five or more years earlier.

Fur thermore, "most" of the postapproval trials that showed clinical benefit
relied on surrogate measures rather than
clinical outcomes, the authors note,
indicating that the same limitations of the
pre-approval trials (not using blinding,
randomization or comparator groups) exist
in the post-approval trials.
That's the summation of a paper*
published in the current issue of J. of the
American Medical Assn. An accompanying
g u e s t e d i to r i a l by Ro b e r t Ca l i f f o f
* http://jamanetwork.com/journals/jama/
article-abstract/2648631

Duke Univ. School of Medicine asked
whether the data raises "concerns about
whether the US regulatory system has
become too permissive by not requiring
traditional randomized controlled trials"
for postmarketing evaluations. He also
notes that "because of the complexity of
diseases and therapies, the vast majority
of biomarkers are not good surrogates for
improved patient outcomes."
Faster FDA
To patient advocates and others seeking
quicker access to investigational drugs,
the results say that there's a better system

in place; to industry critics, the results
say that FDA is bending the rules around
gold-standard, scientifically sound clinical
research. The mixed message probably isn't
going to slow down the trend toward faster
approvals, sought by, among others, the
new FDA Commissioner Scott Gottlieb,
but it will create challenges for healthcare
providers making life-and-death decisions
about therapies. For the pharma industry,
the opportunity for faster market access
will be balanced against the risk of a highly
publicized drug introduction suddenly
going south.

Mylan finalizes a DoJ settlement over EpiPen pricing
Observers are critical of the $465-million penalty as too lenient
There's a certain messy, "drain the
swamp" vibe around the entire settlement
pro cess b e tween My lan and the US
government over the resolution of Mylan's
misclassification of its EpiPen product,
which was approved as a branded product
but sold by Mylan for years as a generic.
Under Medicaid rules, both types of
pharma products are discounted when sold
into Medicaid programs, but the branded
discount (23.1%) is higher. Because Mylan
had classified the product as a generic, it
overcharged state and federal Medicaid
programs to the tune of $1.27 billion during
2006-2016, according to an OIG report.
Nevertheless, in a final settlement
announced on Aug. 17, Mylan will pay a
penalty of $465 million, the figure agreed
to on a preliminary basis last October. "This
settlement demonstrates the Department of
Justice's unwavering commitment to hold
pharmaceutical companies accountable for
schemes to overbill Medicaid," said Acting

Assistant Attorney General Chad Readler of
the DoJ's Civil Division.
"Mylan has always been committed to
providing patients in the US and around
the world with access to medicine, and we
look forward to continuing to deliver on
this mission," said Heather Bresch, Mylan
CEO, in a statement released after the
settlement. There is no admission of guilt
in the settlement, and EpiPen is now being
treated as a branded product for Medicaid
discounting. Mylan will also operate under
a five-year corporate integrity agreement
with DoJ.
But Sen. Charles Grassley (R-IA),
a legislator who keeps a constant eye on
pharma industry practices, criticized the
settlement in a statement his office released:
"It looks like the settlement amount
shortchanges the taxpayers ... [DoJ]
doesn't say how it arrived at $465 million
for a similar time period. Did the Justice
Department consider the inspector general

estimate? If not, why not?"
Whistleblower: Sanofi
Another detail not generally
acknowledged when the initial settlement
was reached last year is that it came about
through a qui tam whistleblower claim by
Sanofi, makers of a different epinephrine
injector, the Auvi-Q. Sanofi will garner $38.7
million from the settlement under False
Claims Act rules. "We commend Sanofi for
bringing this matter to our attention," noted
the DoJ statement. Apparently, it had been
known at CMS for years what Mylan was
doing, but no action was taken until the
Sanofi suit was filed in 2014.
Mylan's EpiPen stirred up a hornet's nest
of controversy last year, when consumers
buying the product (which is an emergency
treatment for allergic shock) found that
the product was now priced at $600 per
prescription. Congressional hearings
revealed that Mylan had raised the product's

price by some 550% since it acquired it in
the mid-2000's-this for a product that has
changed very little over the years. Bresch
contended, among other things, that the
price increases are due in part to pressure
from pharmacy benefit managers who
demand (and retain) a larger rebate each
year from the drug. That claim (which has
been aggressively disputed) started a focus
on PBM marketing practices that continues
to this day.
In turn, Mylan began to market an
authorized generic version of its own
product, at a significantly lower price.
Press reports indicate that Mylan has
lost significant market share (from 95%
to around 70%) for both types of EpiPen
products; the company missed analyst
estimates of profitability in the latest quarter,
and in mid-August, its stock is down by
almost a third from year-ago levels, in a
period where most generic manufacturers
are seeing similar downturns.

September | October 2017 Visit our website at www.PharmaceuticalCommerce.com 9


http://www.jamanetwork.com/journals/jama/article-abstract/2648631 http://www.jamanetwork.com/journals/jama/article-abstract/2648631 http://www.PharmaceuticalCommerce.com

Table of Contents for the Digital Edition of Pharmaceutical Commerce - September/October 2017

Table of Contents
Pharmaceutical Commerce - September/October 2017 - Cover1
Pharmaceutical Commerce - September/October 2017 - Cover2
Pharmaceutical Commerce - September/October 2017 - Table of Contents
Pharmaceutical Commerce - September/October 2017 - 4
Pharmaceutical Commerce - September/October 2017 - 5
Pharmaceutical Commerce - September/October 2017 - 6
Pharmaceutical Commerce - September/October 2017 - 7
Pharmaceutical Commerce - September/October 2017 - 8
Pharmaceutical Commerce - September/October 2017 - 9
Pharmaceutical Commerce - September/October 2017 - 10
Pharmaceutical Commerce - September/October 2017 - 11
Pharmaceutical Commerce - September/October 2017 - 12
Pharmaceutical Commerce - September/October 2017 - 13
Pharmaceutical Commerce - September/October 2017 - 14
Pharmaceutical Commerce - September/October 2017 - 15
Pharmaceutical Commerce - September/October 2017 - 16
Pharmaceutical Commerce - September/October 2017 - 17
Pharmaceutical Commerce - September/October 2017 - 18
Pharmaceutical Commerce - September/October 2017 - 19
Pharmaceutical Commerce - September/October 2017 - 20
Pharmaceutical Commerce - September/October 2017 - 21
Pharmaceutical Commerce - September/October 2017 - 22
Pharmaceutical Commerce - September/October 2017 - 23
Pharmaceutical Commerce - September/October 2017 - 24
Pharmaceutical Commerce - September/October 2017 - 25
Pharmaceutical Commerce - September/October 2017 - 26
Pharmaceutical Commerce - September/October 2017 - 27
Pharmaceutical Commerce - September/October 2017 - 28
Pharmaceutical Commerce - September/October 2017 - 29
Pharmaceutical Commerce - September/October 2017 - 30
Pharmaceutical Commerce - September/October 2017 - 31
Pharmaceutical Commerce - September/October 2017 - 32
Pharmaceutical Commerce - September/October 2017 - 33
Pharmaceutical Commerce - September/October 2017 - 34
Pharmaceutical Commerce - September/October 2017 - Cover3
Pharmaceutical Commerce - September/October 2017 - Cover4
https://www.nxtbook.com/nxtbooks/pharmcomm/202006
https://www.nxtbook.com/nxtbooks/pharmcomm/202003
https://www.nxtbook.com/nxtbooks/pharmcomm/201911
https://www.nxtbook.com/nxtbooks/pharmcomm/201909
https://www.nxtbook.com/nxtbooks/pharmcomm/201906
https://www.nxtbook.com/nxtbooks/pharmcomm/201903
https://www.nxtbook.com/nxtbooks/pharmcomm/201811
https://www.nxtbook.com/nxtbooks/pharmcomm/201809
https://www.nxtbook.com/nxtbooks/pharmcomm/201806
https://www.nxtbook.com/nxtbooks/pharmcomm/20180304
https://www.nxtbook.com/nxtbooks/pharmcomm/20171112
https://www.nxtbook.com/nxtbooks/pharmcomm/20170910
https://www.nxtbook.com/nxtbooks/pharmcomm/20170708
https://www.nxtbook.com/nxtbooks/pharmcomm/20170506
https://www.nxtbook.com/nxtbooks/pharmcomm/20170304
https://www.nxtbook.com/nxtbooks/pharmcomm/20170102
https://www.nxtbook.com/nxtbooks/pharmcomm/20161112
https://www.nxtbook.com/nxtbooks/pharmcomm/20160910
https://www.nxtbook.com/nxtbooks/pharmcomm/20160708
https://www.nxtbook.com/nxtbooks/pharmcomm/20160506
https://www.nxtbook.com/nxtbooks/pharmcomm/20160304
https://www.nxtbook.com/nxtbooks/pharmcomm/20160102
https://www.nxtbook.com/nxtbooks/pharmcomm/20151112
https://www.nxtbook.com/nxtbooks/pharmcomm/20150910
https://www.nxtbook.com/nxtbooks/pharmcomm/20150708
https://www.nxtbook.com/nxtbooks/pharmcomm/20150506
https://www.nxtbook.com/nxtbooks/pharmcomm/20150304
https://www.nxtbook.com/nxtbooks/pharmcomm/20150102
https://www.nxtbook.com/nxtbooks/pharmcomm/20141112
https://www.nxtbook.com/nxtbooks/pharmcomm/coldchaindirectory2014
https://www.nxtbook.com/nxtbooks/pharmcomm/20140910
https://www.nxtbook.com/nxtbooks/pharmcomm/20140708
https://www.nxtbook.com/nxtbooks/pharmcomm/20140506
https://www.nxtbook.com/nxtbooks/pharmcomm/20140304
https://www.nxtbook.com/nxtbooks/pharmcomm/20140102
https://www.nxtbook.com/nxtbooks/pharmcomm/dataservicedirectory
https://www.nxtbook.com/nxtbooks/pharmcomm/20131112
https://www.nxtbook.com/nxtbooks/pharmcomm/20130910_hubreport
https://www.nxtbook.com/nxtbooks/pharmcomm/20130910
https://www.nxtbook.com/nxtbooks/pharmcomm/20130708
https://www.nxtbook.com/nxtbooks/pharmcomm/20130506
https://www.nxtbook.com/nxtbooks/pharmcomm/coldchain2013
https://www.nxtbook.com/nxtbooks/pharmcomm/20130304
https://www.nxtbook.com/nxtbooks/pharmcomm/20130102
https://www.nxtbook.com/nxtbooks/pharmcomm/20121112
https://www.nxtbook.com/nxtbooks/pharmcomm/20120910
https://www.nxtbook.com/nxtbooks/pharmcomm/20120708
https://www.nxtbook.com/nxtbooks/pharmcomm/20120506
https://www.nxtbook.com/nxtbooks/pharmcomm/20120506_coldchain
https://www.nxtbook.com/nxtbooks/pharmcomm/20120304
https://www.nxtbook.com/nxtbooks/pharmcomm/20120102
https://www.nxtbook.com/nxtbooks/pharmcomm/20111112
https://www.nxtbook.com/nxtbooks/pharmcomm/20110910
https://www.nxtbook.com/nxtbooks/pharmcomm/20110708
https://www.nxtbook.com/nxtbooks/pharmcomm/20110506
https://www.nxtbook.com/nxtbooks/pharmcomm/20110304
https://www.nxtbook.com/nxtbooks/pharmcomm/20110102
https://www.nxtbook.com/nxtbooks/pharmcomm/20101112
https://www.nxtbook.com/nxtbooks/pharmcomm/20100910
https://www.nxtbook.com/nxtbooks/pharmcomm/20100708
https://www.nxtbook.com/nxtbooks/pharmcomm/20100506
https://www.nxtbook.com/nxtbooks/pharmcomm/201004
https://www.nxtbook.com/nxtbooks/pharmcomm/201003
https://www.nxtbook.com/nxtbooks/pharmcomm/20100102
https://www.nxtbook.com/nxtbooks/pharmcomm/20091112
https://www.nxtbookmedia.com