GLOBAL REPORT 2012
`
`Merck’s Januvia raced to diabetes dominance in many countries. But it’s a different game among
`combination products and in emerging markets, as competitors seize rostrum spots in their quest for
`gliptin gold. Sarah Rickwood and Carolyn Gauntlett reveal opportunities for competitive advantage
`
`THE DIABETES
`OLYMPICS
`The market for non-insulin diabetes treatments has experienced strong growth over the last decade, averaging
`
`9.5% over the past five years. Epidemiology and unmet need have combined to generate demand for new
`product classes. The first of these, the DPP-IV class, is dominated by Merck’s Januvia, but further launches
`are lining up in another major new class, the SGLT-2s.
`Given the similarities in the competitive characteristics of this new class compared to the DPP-IVs, there may
`be significant learning opportunities from the successes and failures of recent oral diabetes agent launches—
`knowledge that companies can apply to gain advantage in a highly competitive field.
`Type II diabetes, paradoxically, is dominated by old and off-patent drugs in the early stages of treatment, but
`remains a significant growth opportunity for new patented products because of the progressive nature of the disease,
`and considerable remaining unmet need. DPP-IVs, therefore, offered a new alternative in the treatment pathway,
`post metformin alone and prior to the later stages of treatment with insulins, or, latterly, GLP-1s pre-insulin.
`These diabetes medicines have been the primary success story over the last five years, capturing 33% of
`worldwide value sales of non-insulin, anti-diabetic products. In the eight mature markets, DPP-IVs account for
`a significant percentage of value growth in diabetes treatments.
`The first DPP-IV inhibitor to enter the market was Januvia (sitagliptin), introduced in 2006 in the US by Merck.
`Today, Januvia dominates sales of DPP-IV products in developed markets, with the brand accounting for about
`80% of worldwide sales for single-compound products. Januvia’s success can be attributed to both an excellent
`commercialization plan from Merck and a strong element of serendipity.
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`mmm-online.com x AUGUST 2012 x MM&M 35
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`AstraZeneca Exhibit 2141
`Mylan v. AstraZeneca
`IPR2015-01340
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`THE DIABETES OLYMPICS
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`Fig. 1: A second chance to unseat the champ
`In emerging markets, Novartis’s Galvus and Eucreas account for more than 50% of the DPP-IV market. Share, by country, according to 2011 sales*
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`100
`
`80
`
`60
`
`40
`
`20
`
`0
`
`BRAZIL
`
`INDIA
`
`Galvus
`
`Eucreas
`
`RUSSIA
`
`CHINA
`
`USA
`
`Januvia
`
`Janumet
`
`Onglyza
`
`Tradjenta
`
`Kombiglyze ER
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`* Galvus launched Jan. 2012 in China, so no sales data as yet. Galvus and Eucreas not launched in US. Indian sales include all local brands.
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`Source: IMS Health MIDAS MAT Dec 2011
`
`Januvia could have launched in direct competition to Novartis’
`Galvus (vildagliptin) in the US, but shortly before launch, Galvus
`was delayed, a consequence of side-effect concerns. This left the field
`open to Januvia, allowing it to enjoy three years of US exclusivity
`in its class before AstraZeneca/Bristol-Myers Squibb introduced
`Onglyza (saxagliptin).
`During this time, Merck aggressively promoted Januvia to gain
`early buy-in from stakeholders and to build a positive brand image.
`Januvia secured its place as “the” gliptin, an image
`followers have found hard to challenge despite
`comparable promotional spending. Similar market
`dynamics occurred in Europe, where Januvia was
`launched in 2007. Galvus hit the European market
`in 2008, but has managed sales of just 9% com-
`pared to Januvia.
`
`Fixed-dose combinations offer a sec-
`ond chance to be first
`While it’s been standard for single-compound
`oral agents to be followed by combinations of
`those agents, most frequently with metformin,
`these products have been follower, second
`brands—with less importance and potential
`than the original single agent. However, with
`the DPP-IVs, combination products have posed
`an opportunity to gain competitive advantage.
`In major European markets, Novartis launched
`its combination product, Eucreas (vildagliptin/
`metformin), concurrently with Galvus. While
`Galvus was the second-to-market single-com-
`pound product, Eucreas was the first launched
`combination DPP-IV product.
`In contrast, Merck delayed launching its fixed-
`dose combination product, Janumet (sitagliptin/
`metformin), until a year after Januvia’s launch.
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`36 MM&M x AUGUST 2012 x mmm-online.com
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`This meant that Janumet was the second-to-market combination
`product. Although uptake of Eucreas did not match that of Janumet
`across the top five European countries—likely because Janumet ben-
`efited from Januvia’s established patient base—Eucreas performed
`significantly better than Galvus in most European markets.
`The competitive success of Eucreas versus Galvus raises questions
`about the relative importance of single-compound products versus
`combination products in overall diabetes brand success. After two
`years on the market in France, Germany and Spain,
`Eucreas represents 85-90% of vildagliptin family
`sales. In contrast, Janumet represents 40-60% of
`sitagliptin family sales. In the first quarter post
`launch, Novartis’ promotional spending on Eucreas,
`as audited by IMS Health, was three times higher
`than it was for Galvus.
`In the US, Merck was first to market with both
`Januvia and Janumet. The second combination
`product to come to market was Kombiglyze XR,
`which has not been able to compete with Janu-
`met’s first-mover advantage and has seen poor
`uptake. In 4Q 2011, Kombiglyze XR accounted
`for just 2% of the DPP-IV market, compared
`with 16% for Janumet.
`
`Pharmerging markets: A different game
`Pharmerging markets (a term coined by IMS to
`include 17 countries with income levels under
`$25,000 per capita and relatively rapid growth)
`account for most of the volume potential of the
`diabetes market, driven by growing and aging
`populations acquiring Western habits. But they
`have, until now, accounted for very little dia-
`betes market value, and less of the global sales
`of recently launched agents. This is starting to
`change with the battle among the DPP-IVs.
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`In Brazil, Russia and India, Merck’s Januvia was launched before
`Novartis’s Galvus. Nonetheless, Novartis’ family of products account-
`ed for more than 50% of the DPP-IV market in 2011 (see Fig. 1),
`mostly thanks to Eucreas, which has outperformed Janumet consid-
`erably. Meanwhile, Galvus has held its own against Januvia.
`Pharmerging markets offer a new opportunity for diabetes
`launches, and the opportunity to overturn the competitive dynam-
`ics seen in the established markets. The first opportunity is one of
`size. In 2011, combined sales for non-insulin anti-diabetics (albeit
`both generic and branded) across BRIC were higher than sales in
`Germany, France and the UK.
`Additionally, pharmerging markets experienced average annual
`growth of 26% for diabetes products from 2007-2011. The second
`opportunity is to employ different approaches to commercialization:
`winning in pharmerging markets is driven by adaptation to the local
`environment, not by mature market success.
`Local issues and knowledge have had a significant impact on the
`success of DPP-IVs in pharmerging markets. In Brazil, Novartis
`heavily promoted Galvus and launched both plain and combination
`products together. This helped Novartis achieve sales for its DPP-IVs
`that were 40% higher than Merck’s Januvia family in 2011.
`Additionally, the importance of local knowledge means that “going
`it alone” may not be an effective strategy. In late 2008, Novartis
`joined forces with a local partner, USV, to co-promote Galvus in
`India. Local branding of the product as Jalra and a large sales force
`resulted in fast market penetration. In contrast, Merck waited until
`after Novartis launched Galvus to increase its sales force and partner
`with Sun Pharma to launch the local brand Istamet.
`
`Differentiation: How much is enough?
`IMS’s research program of interviews with key opinion leaders
`(KOLs), providers and payers suggests that recent DPP-IV launches
`have lacked clear points of differentiation in these stakeholders’ eyes,
`despite significant clinical investment. However, given the size of the
`global diabetes market, even small patient niches represent valuable
`opportunities and new products can be targeted to capture them.
`Boehringer Ingelheim targeted a niche patient population—those
`with renal impairment—with Tradjenta (linagliptin), because the
`product is not excreted via the kidneys. While the jury is still out in the
`US on Tradjenta’s market performance, the product is experiencing
`slow uptake in Europe due to differentiation not being achieved.
`Additionally, Onglyza received supplementary approval for the
`same patient group; and the German Institute for Quality and Effi-
`ciency in Health Care (IQWiG) failed to find that Tradjenta provided
`an added benefit, resulting in Boehringer Ingelheim choosing not
`to launch in Germany rather than accept a sub-optimal price with
`wider European ramifications.
`Several combination products that have recently launched have
`delivered lesser initial performance because their main differentia-
`tion, convenience and compliance, were simply not a strong enough
`sell. For example, Merck’s Juvasync (sitagliptin and simvastatin) has
`struggled because patients still have to take metformin with it.
`Four more DPP-IV inhibitor products are in late-stage develop-
`ment. 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 chase ever-decreasing
`portions of the market in most countries, and at best achieve limited
`success in certain markets.
`
`uerosTo commodo odionul
`
`Lessons learned from long-distance launches
`Four more DPP-IV inhibitor products 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 chase ever-decreasing portions of the
`market in most countries, and at best achieve limited success in certain
`markets. The next major class of diabetes drugs—sodium-glucose
`transporter inhibitors (SGLT-2s)—are likely to experience market dynam-
`ics that mirror those of the DPP-IV inhibitors. Here are some tips for new
`entrants
`First-to-market products
`
`competitors—and launch combination products quickly in mature
`markets to reduce the opening for rivals.
`
`1 Capitalize on the position—promoting heavily prior to the launch of
`2 Leverage pharmerging markets. Form alliances with local compa-
`3 As competitive products enter, emphasize homogeneity in the class
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`nies and consider local branding. Local partners can help shield a
`product from negative attitudes directed toward the sponsor.
`
`as a whole, since physicians tend not to switch patients off of exist-
`ing therapy for a clinically comparable product.
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`Late-to-market products
`
`ing markets may present opportunities to be first, especially for
`combination products.
`
`1 Look beyond the largest markets for sales opportunities. Pharmerg-
`2 Ensure that points of differentiation are really clinically relevant.
`3 Ensure that other differentiators, such as those that deliver patient
`
`This will be an issue for the follower DPP-IV and SGLT-2 brands, the
`majority of which KOLs have had trouble distinguishing.
`
`convenience, will be recognized and appreciated by prescribers
`and patients.
`
`Future diabetes classes: Sodium-Glucose Transporter
`Inhibitors (SGLT-2s)
`With an abundance of treatments for Type II diabetes in the pipe-
`line, companies should be looking to apply the lessons of recent
`launches (see sidebar). The next major class of drugs—sodium-glucose
`transporter inhibitors (SGLT-2s) —are likely to experience market
`dynamics that mirror those of the DPP-IV inhibitors.
`A large number of these molecules are in late-stage development
`and are expected to launch around the same time. Like the DPP-IV
`inhibitors, IMS KOL interviews suggest the SGLT-2s may not be
`clearly differentiated from one another in the eyes of prescribers in
`terms of safety, efficacy or convenience. The first-to-market product
`will therefore, as with Januvia, have a significant advantage.
`European approval for AstraZeneca/BMS’s dapagliflozin suggests
`that this agent will be the beneficiary here; however it may still be
`possible for late-to-market products to succeed if they learn the
`lessons of the DPP-IVs. n
`
`Sarah Rickwood is director, European thought leadership group,
`and Carolyn Gauntlett is consultant, European thought leadership
`group, IMS Health.
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