Launch Excellence in the Diabetes Market: Lessons from - IMS Health

Launch Excellence
in the Diabetes Market
Lessons from History
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Growth in the market for Type II Diabetes treatments has consistently
out-performed the pharmaceutical market as a whole, and IMS believes that
this will continue for the next decade, driven by the obesity epidemic, an
aging population, and the advent of new therapies. In fact, in IMS’s
perspective, diabetes stands out as one of the elite group of major therapy
areas that will continue to outperform the market as a whole to 2016. Within
this out-performing group, it is also the only primary-care-driven therapy
area of any size, the others being specialist areas.
However, while epidemiology and unmet need mean there are multi-billion
dollar opportunities for successful launches and many potential contenders
for blockbuster status, success is still not a foregone conclusion.
IMS has studied the launch strategies and subsequent market performance of
the frontrunner products in the dipeptidyl peptidase IV (DPP-IV) therapeutic
class worldwide to understand what separates clear market leaders from those
with less impressive sales. From this, we’ve drawn key learnings pertinent to
companies preparing to launch one of the many products currently in
development for Type II Diabetes.
THE NEXT DECADE: A CROWDED FIELD
Over the next ten years, most of the new therapies introduced for Type II Diabetes will
cluster in just a few drug classes, meaning that the market will see a small number of
first-in-class launches followed by an avalanche of follower brands. These follower
products will naturally face a challenging launch environment if they cannot
demonstrate value propositions that are differentiated from first-in-class products in
the eyes of clinical opinion leaders, prescribers, and payers.
Nevertheless, experience has shown that companies whose products are not first to
market can still win—in specific segments or countries. Here, we examine how various
strategies have played out for companies marketing DPP-IV inhibitors and consider
the implications for products in the pipeline.
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DPP-IVs: CHANGING THE TREATMENT REGIMEN
Of the two recent new product classes to treat Type II Diabetes, the oral DPP-IVs and
the injectable GLP-1s, DPP-IV inhibitors stand out for their success in overall sales
levels, as they are used earlier and for a broader group of patients than the GLP-1s.
Although there is a range of existing oral diabetes therapies, the fact that no class
provides a definitive therapeutic approach to the disease means there is always
opportunity for new classes of oral agents for patients post metformin monotherapy.
DPP-IVs came into a largely generic oral market where the only on-patent oral agents,
the Thiazolidinediones (TZDs), were approaching loss of exclusivity, with one of the
two members of the class, Avandia ® (rosiglitazone), facing a major question on safety.
The first DPP-IV inhibitor on the market was Januvia ® (sitagliptin), introduced in the
U.S. in 2006 by Merck & Co. (Novartis’s Galvus ® (vildagliptin) was delayed in the U.S.
due to questions of side effects). Since then, further DPP-IVs, Onglyza ® (saxagliptin)
and Tradjenta (linagliptin) have also entered the market, and the pipeline promises
more to come.
In the five years since, DPP-IVs have captured 33 percent of worldwide sales of
non-insulin, anti-diabetic products. And in the mature eight markets, DPP-IVs
account for 58 percent of the value growth in diabetes treatments.
JANUVIA: FIRST TO MARKET TAKES ALL
Januvia now dominates sales of DPP-IV products in developed markets. In 2011, the
brand accounted for approximately 80 percent of worldwide sales for plain DPP-IV
inhibitors. Later launches in the class—such as Onglyza and Galvus—have been unable
to unseat Januvia from its leadership position.
In the U.S., Januvia enjoyed three years of exclusivity in its class before
AstraZeneca/BMS introduced Onglyza. During this time, Januvia used strong
promotion to gain early buy-in from stakeholders and to build a positive brand image.
It secured its place as “the” gliptin, an image that AstraZeneca/BMS was unable to
change despite heavy U.S. promotional investment.
Similar market dynamics occurred in Europe where Januvia was launched in 2007.
Here, the next plain DPP-IV inhibitor to be launched was Galvus, in 2008. Since then
Galvus has achieved sales of just 12 percent of those seen for Januvia in Europe.
Januvia’s success is particularly meaningful because the brand has not demonstrated
any clinically relevant differentiation over other products in the class 1 . This suggests
that the variance in performance within the class was aided by Januvia’s position as
first in class. Januvia was in the right place at the right time, and when subsequent
entries came along, physicians generally did not move from their first gliptin choice.
FOOTNOTE:
1 Key opinion leaders were unaware of any differentiation between products in the class, and the only head-to-head trial in the class showed
Januvia’s 100mg “non-inferiority” compared to Onglyza 5 mg. Source: IMS interviews with Key Opinion Leaders as part of IMS’s Therapy
Prognosis research program.
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FIXED-DOSE COMBINATIONS: A SECOND CHANCE TO BE FIRST
Whilst it has been standard for plain oral agents to be followed by their combination
with metformin, for TZDs these products were very much second brands. With the
gliptins, the launch of the combination has been an opportunity to gain competitive
advantage.
In the major European markets, Novartis launched its combination product, Eucreas ®
(vildagliptin/metformin), concurrently with its plain product, Galvus. So, while
Galvus was the second-to-market plain product, Eucreas was the first launched
combination DPP-IV product. (See Fig. 1).
FIGURE 1: LAUNCH OF FIRST COMBINATION DPP-IVs IN THE EU
2008 2009 2010
Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar
Eucreas launched 2 yrs ahead of Janumet in UK
In contrast, Merck delayed launching its fixed-dose combination product, Janumet®
(sitagliptin/metformin) until a year after Januvia, its single-compound product, was
on the market. This meant that Janumet was the second-to-market combination
product. In fact, it lagged behind Eucreas by a full two years in the U.K.
Uptake of Eucreas did not match that of Janumet across the top five European
countries—likely because Janumet benefited from Januvia’s established patient base.
(See Fig. 2.) However, within Novartis’s product family, Eucreas performed
significantly better than Galvus in most European markets. This is most apparent in
Spain where in 2011, Eucreas and Galvus accounted for 34 percent and 3 percent of
the DPP-IV inhibitor market, respectively. Sales for Eucreas amounted to 83% of
Janumet sales, far exceeding Galvus’ performance. The lesson here is that it might
well be worthwhile to give as much—if not greater—focus to the launch of the
combination product as to the launch of the plain product.
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FIGURE 2: DPP-IV SALES/SHARE FOR SINGLE AND COMBINATION PRODUCTS IN EU
Share Market
SHARE OF SALES BY COUNTRY* 2011 IN US$
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
2%
7%
3%
6%
5%
10%
3%
3%
5%
8%
14%
19%
15% 34%
6%
4%
31%
45%
41%
32%
37%
34%
41%
19%
France Germany Italy Spain UK
*Includes licensed brands across Europe
79%
Galvus
Onglyza
Eucreas
Janumet
Januvia
CUMULATIVE SALES OVER TIME, EU5*
The competitive success of Eucreas versus Galvus raises questions about the relative
importance of the plain and combination products in overall diabetes brand success.
Novartis’ combination product (Eucreas) is a far bigger proportion of vildagliptinbased
sales than Merck’s combination product (Janumet) is of sitagliptin-based
products. After two years on the market in France, Germany, and Spain, for example,
Eucreas represents 85-90 percent of vildagliptin family sales. In contrast, Janumet
represents 40-60 percent of sitagliptin family sales two years after the launch.
Indeed, with a sub-optimal plain product launch, Novartis concentrated its
promotional spending on Eucreas. In the first quarter post launch, the company’s
promotional spending (as reported in IMS audits) on Eucreas was three times higher
than it was for Galvus.
In the U.S., the situation was different in that Merck’s products were the first to
market both for the single-compound therapy (Januvia) and the combination therapy
(Janumet). The second combination product to come on the scene was Kombiglyze
XR. (Kombiglyze XR contains saxagliptin and metformin and was launched by BMS
with AstraZeneca.) Kombiglyze XR has not been able to combat Janumet’s first-mover
advantage and has seen poor uptake. In Q4 2011, Kombiglyze XR only accounted for
two percent of the DPP-IV market, compared with 23 percent for Janumet.
So, for both Novartis in Europe and Merck in the U.S., there was a clear advantage to
being first on the market with the combination product—whether or not the same
company was first to market with the plain product.
Companies whose products are not first to market can maximize their
potential sales by pursuing specific strategies.
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Cumulative Sales, LCUS$ m
1,100
1,000
900
800
700
600
500
400
300
200
100
0
Q3 2007
Q6 2007
Q9 2007
Q12 2007
Q3 2008
Q6 2008
Q9 2008
Q12 2008
Q3 2009
Q6 2009
Q9 2009
Q12 2009
Q3 2010
Q6 2010
Q9 2010
Q12 2010
Q3 2011
Q6 2011
Q9 2011
Q12 2011
*European sales include local branding of Xelevia, Tesavel, Ristaben, Velmetia, Efficib, Ristfor, Zomarist, Icandra, Jalra and Xiliarx assigned
accordingly to Januvia, Janumet, Eucreas and Galvus.

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PHARMERGING MARKETS: A DIFFERENT GAME
The dynamics for first-to-market products are less rigid in the Tier 1 and Tier 2
pharmerging markets than we’ve observed in developed markets. In Brazil, Russia,
and India, for example, Merck’s Januvia was launched before Novartis’s Galvus.
Nevertheless—and unlike mature markets—Novartis’s family of products accounted
for more than 50 percent of the DPP-IV market in 2011. (See Fig. 3) Most of this
success is attributable to Eucreas, which has outperformed Janumet considerably.
Meanwhile, Galvus has held its own against Januvia; its uptake has been comparable
to that of Januvia in Brazil and Russia, and greater than Januvia in India.
FIGURE 3: SPLIT OF DPP-IV CLASS VALUE SALES BY COUNTRY 2011 IN US$*
Share of Market
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
6%
35%
36%
3%
20%
EU5
1%
2%
10%
23%
63%
1%
9%
4%
1%
10%
• In Brazil Galvus and Eucreas
launched at the same time;
21%
24%
17%
Janumet lagged Januvia
• Galvus embarked on a
16%
16%
17%
broader effort to promote
than Januvia
15%
38%
55%
USA Brazil Russia India
Tradjenta
Kombiglyze XR
Onglyza
Janumet
Januvia
Galvus
Eucreas
*Galvus launched Jan 2012 in China so no sales data as yet. Galvus and Eucreas not launched in USA. Indian sales include local branding of
Jalra, Jalra-M, Zomelis, Zomelis-M, Istamet and Istavel assigned accordingly to Galvus, Eucreas, Januvia and Janumet.
A number of interacting factors cause the differences in market dynamics between
mature and pharmerging markets. The first is that companies may focus on mature
markets at the expense of pharmerging markets based on assumptions about where
the best return on investment may be achieved. It is time to revisit these assumptions,
considering that in 2011, combined sales for non-insulin anti-diabetics across BRIC
were higher than they were in each of Germany, France, or the UK. What is more,
these pharmerging markets experienced an average annual growth of 26 percent for
diabetes products from 2007-2011—a rate that is expected to continue. Although
generic products currently dominate the pharmerging markets, growth of branded
product sales is stellar, at 38 percent between 2010 and 2011.
Local issues and local knowledge are also likely to have a big impact on the relative
success of different DPP-IVs in the pharmerging markets. Novartis’s vildagliptin
family of products gained the upper hand in Brazil for a number of reasons. Novartis
promoted Galvus more heavily than Merck promoted Januvia, and Novartis launched
its two vildagliptin-based products together (whereas Merck launched Janumet after
Januvia). These factors combined to help Novartis achieve sales for its family of DPP-
IVs that were 40 percent higher in 2011 than Merck’s were for the Januvia family.
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27%
29%
100%
China

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Another opportunity is to employ different approaches to commercialization: winning
in pharmerging markets is driven by adaptation to the local environment, not by the
precedent of mature market success. In pharmerging markets, the importance of local
knowledge means that “going it alone” may not be an effective strategy. This is
illustrated in the different approaches and outcomes for Novartis and Merck in India.
In late 2008, Novartis joined forces with a local partner, USV, to co-promote Galvus
and Eucreas. Local branding of the products as Jalra and Jalra-Met and a large sales
force led to fast market penetration. In contrast, Merck did not capitalize on its firstto-market
position, but waited until after Novartis launched Galvus to increase its
sales force. Eventually, three years after launching Januvia and more than two years
after the Novartis/USV agreement, Merck partnered with Sun Pharma. Together they
launched local brands, Istamet and Istamel, in 2011. This was too late to unseat
Novartis’s products, however. In 2011, Novartis’s family of products had secured
56 percent of the Indian DPP-IV market, compared with 34 percent for Merck’s family
of products.
DIFFERENTIATION: HOW MUCH IS ENOUGH?
IMS’s research with Key Opinion Leaders, providers, and payers suggest that recent
DPP-IV launches have lacked clear and meaningful points of differentiation in the
eyes of prescribers and patients, despite manufacturers’ efforts to the contrary. IMS
Therapy Forecaster interviews suggest that physicians tend to believe that “all DPP-
IV inhibitors are the same”. That is, they do not see the differentiation that exists as
being clinically meaningful. Onglyza, for example, is more potent than Januvia and
Galvus, but the lower doses required with this product do not improve efficacy or
safety. The distinction, therefore, doesn’t register with physicians.
Patients, too, are difficult to sway. Kombiglyze XR is taken once daily, compared with
twice daily for Janumet. From the uptake of Kombiglyze XR in the U.S., however, it
would appear that patients do not value this additional convenience enough to switch
medications.
Given the size of the global diabetes market, segments of the diabetes population
represent valuable opportunities, and new products can be targeted to capture them.
But, this strategy, too, is fraught with challenges. Boehringer Ingelheim targeted a
niche patient segment—those with renal impairment—with Tradjenta because the
product is not excreted via the kidneys, unlike other DPP-IV inhibitors at the time.
Although it remains to be seen if this product will be successful in the U.S., it is
experiencing slow uptake in Europe following two blows. First, Onglyza received
supplementary approval for the same patient group. Second, the German Institute for
Quality and Efficiency in Health Care (IQWIG) failed to find that Tradjenta provided
an added benefit and ruled that it should be compared not only against other DPP-IV
inhibitors, but against other diabetic agents. This resulted in Boehringer Ingelheim
choosing not to launch in Germany rather than accept a sub-optimal price, with wider
European ramifications.
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Several combination products that have recently launched have struggled because the
convenience of the combination was simply not great enough for patients. Merck’s
Juvasync (sitagliptin and simvastatin) is a case in point. Patients still have to also
take metformin along with it, and so it is no more convenient to take Juvasync plus
metformin than to take Janumet and a separately administered statin. It could also be
that patients and physicians prefer a regimen consisting of Janumet and a separately
administered statin, since more recent statins (such as atorvastatin) may be preferred
(and are now generic).
Although differentiation of the follower products has not worked for the DPP-IVs, in
the injectable GLP-1 segment of the diabetes market, the follower product, Novo
Nordisk’s Victoza ® , has in fact done better than the first to market agent,
Amylin/Lilly's Byetta. Here, Victoza had some clear points of differentiation to Byetta,
including once daily administration because of a longer half life, less risk of
immunogenicity because it was fully humanized, and a superior performance in
lowering blood-sugar levels in head-to-head trials. The lesson here is that
differentiation of the follower can work if it is seen as clinically meaningful by
prescribers and payers and if benefits cannot be taken as a “class effect,” shared by all
members of that class.
Four more DPP-IV inhibitors are in late-stage development. The lessons of the first
four products strongly suggest that, unless there is true differentiation backed up with
a very effective campaign across stakeholders, they are likely to be chasing ever
decreasing portions of the market in most countries, and at best will achieve limited
success in certain markets, such as the marketing company’s home market.
Given the size of the global diabetes market, even patient niches represent
valuable opportunities.
FUTURE DIABETES CLASSES: FAMILIAR GROUND
There are many companies with up-and-coming treatments for Type II Diabetes in the
pipeline; all should be looking to apply the lessons of recent launches, as history tends
to repeat itself given similar circumstances. And it does seem that the circumstances
surrounding the next major class of drugs about to launch, the sodium-glucose
transporter inhibitors (SGLT-2s), will give us déjà vu...
Products in this class are likely to experience market dynamics that mirror those of the
DPP-IV inhibitors. Multiple examples of these molecules are in late-stage
development and are expected to launch around the same time. As with the DPP-IV
inhibitors, IMS Key Opinion Leader interviews suggest the SGLT-2 inhibitors may not
be clearly differentiated from one another in the eyes of prescribers and payers in
terms of safety, efficacy, or convenience. The first-to-market product will therefore, as
with Januvia, have a significant advantage, and European approval for AZ/BMS’s
dapagliflozin suggest that this agent will enjoy this role; however it may still be
possible for late-to-market products to succeed if they learn the lessons of the DPP-IVs.
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The SGLT-2 inhibitors are destined to be used in later lines, so combinations with
any of the existing diabetes classes could help in securing market share. In order for
these combinations to succeed, though, they must provide a real convenience benefit
to patients.
Successful Strategies for the First to Market
• Do not allow being first to market tempt you into complacency. Capitalize on your
position, promoting heavily to truly “own” the market prior to the launch of
competitors.
• Launch combination products quickly in mature markets to reduce the opening for
competitors to establish a beachhead.
• Don’t neglect pharmerging markets. To maximize your potential in them, form
alliances with local companies and consider local branding. Local partners have
in-depth knowledge of the target market, can furnish local resources, and can
extend sales force reach and make better use of local relationships and knowledge
than their multi-national counterparts.
• As competitors enter, emphasize homogeneity in the class as a whole, since
physicians tend not to switch patients off of existing therapy for a new, but
clinically comparable, product.
Successful Strategies for Late-to-Market Products
• Look beyond the largest markets for sales opportunities. The pharmerging markets
may present opportunities to be first.
• Treat combination products as a second chance to be first. Aim to be first with a
combination product, and consider positioning, branding, and investing in this
product as if it were a completely new launch.
• Identify points of differentiation, but ensure they are truly clinically relevant—and
targeted toward identifiable patient segments and unmet needs.
• Ensure that other differentiators—such as those that deliver patient convenience—
will be recognized and appreciated by prescribers and patients.
It might well be worthwhile to seize the first-to-market advantage with a
combination product, even if you don’t have a single-compound product.
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CONCLUSION
The diabetes market is the single large, predominantly primary-care therapy
area that IMS forecasts will continue to out-perform the pharmaceutical
market as a whole. Accordingly, the success of launches into this market are
of huge importance to many major pharmaceutical companies, and to the
health of the research-based pharmaceutical industry as a whole. Of the many
products in development for Type II Diabetes, only a handful will enjoy firstmover
advantage. That does not mean, however, that every other product
need be an “also ran.” As we’ve seen with the DPP-IV inhibitors, it is possible,
with the right strategy, timing, and resources, to enjoy strong market
performance even as a later entrant.
This point in time—with several major launches completed, but a number still
on the way—is an ideal time to review and reflect upon past experience and
ask what learnings can be applied to improve future diabetes launches. As the
Spanish-American philosopher George Santayana said: “Those who cannot
remember the past are condemned to repeat it.”
For further information, please contact Sarah Rickwood or Carolyn Gauntlett
SRickwood@uk.imshealth.com CGauntlett@uk.imshealth.com
+44 (0)20 3075 5322
www.imshealth.com
We gratefully acknowledge the contributions of James Harris to the development of this white paper
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IMS capabilities in Launch Excellence
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Our proven framework – leveraged successfully
with more than 50 launch teams – ensures
best-in-class diagnostics, planning and tracking
for optimal launch performance. We partner with
clients for their end to end launch consulting
needs or can be flexible to work on selected issues
and areas of focus.
With an offering built on deep functional
knowledge and expertise in more than 90 therapy
areas, we combine the skills and experience of
1,700 IMS consultants across the launch spectrum,
to drive best-practice launch execution and
internal change management for our clients.

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