Valsartan: Exporting France's Success

Novartis' newfound marketing muscle has turned hypertension drug valsartan (Diovan) into a class leader worldwide, with $1.1 billion in sales last year. But the company's experience in France in tailoring its message to individual physicians has proved particularly successful, and provided a model for other countries.

Launched in Germany in 1996 and a year later in the US, Novartis AG 's valsartan (Diovan in much of the world, Tareg in France) was the second angiotensin II receptor antagonist onto the competitive hypertension market after Merck & Co. Inc. 's losartan (Cozaar). Today, with sales annualizing at $1.5 billion, valsartan is class-leader in a group Novartis has since re-labeled "ARBs"—Angiotensin II Receptor Blockers. As Novartis' largest product, valsartan was one of the primary drivers behind the group's 9% sales growth for the first half this year—and the 5% growth in the most recent quarter.

Valsartan's success stems largely from a fundamental overhaul in Novartis' marketing operations during the late nineties under the leadership of Thomas Ebeling, CEO of Novartis' pharmaceutical operations (see "Renewing Novartis," IN VIVO, January 2001, (Also see "Renewing Novartis" - In Vivo, 1 Jan, 2001.)). Novartis' focused clinical trial data, sharpened execution and emphasis on global messages has generated the largest returns in the US hypertension market—worth $11 billion, according to Goldman Sachs—where first half sales grew 19%, generating 43% of Novartis' global pharmaceutical revenues.

But some of the company's best-practice marketing techniques are being pioneered in Europe. France in particular, explains Christopher Kaplan, head of Novartis' cardiovascular and metabolism franchise, bred the company's "differential detailing" approach and is as a result the prime example of how Novartis has "achieved marketing and sales excellence." Differential detailing describes how sales reps closely adjust their marketing message to physicians according to their current prescribing habits and preferences.

The trick to Novartis' detailing, though, lies in not only differentiating valsartan from other ARBs, like losartan and Sanofi-Synthelabo SA's irbesartan (Avapro in the US, Aprovel in France) but also differentiating the entire ARB class from the many other, older classes used in the treatment of hypertension, most particularly the angiotensin converting enzyme inhibitors (ACE inhibitors). (See Exhibit 1.)

Global Clinical Strategy

To back up its differentiation claims, Novartis' French team relies upon the company's extensive portfolio of clinical data generated as part of a global marketing strategy for valsartan.

As well as coining the term "ARB" to eliminate the possible perception that a class called angiotensin-2 blockers was in some way second rate to ACE inhibitors, Novartis is designing and using clinical trials to distinguish the class from other hypertension treatments. In 1997, the company initiated VALUE (Valsartan Anti-hypertensive Long-term Use Evaluation), a six-year trial comparing valsartan with Pfizer's $3.6 billion CCB amlodipine (Norvasc), hoping to show that valsartan is more effective, for the same decrease in blood pressure, at lowering cardiac mortality and morbidity.

As a class, ARBs still have a smaller share of the hypertension market than CCBs and ACEs. Since ACEs offer primary protection from cardiovascular disease, their usage is expanding beyond heart failure and high-risk patients with hypertension. What's more, many of the CCBs and ACE inhibitors (like the CCB diltiazem and the ACE inhibitor enalapril) have gone or are about to go generic and are therefore preferentially prescribed over the newer, more expensive ARBs in some countries.

Cost, and the relative lack of long-term data for the newer class, means ARBs are indicated in most markets mainly for patients who cannot tolerate ACE inhibitors, usually because of their most common side effect, a dry cough seen in as many as 10-15% of patients during trials.

Yet the genericization of ACE inhibitors and CCBs is also good news for ARBs: it means more people are being prescribed these drugs, experiencing the side-effects—and hence switching to ARBs. "With more patients being prescribed generic forms of the older drugs, those patients switching from ACE inhibitors or CCBs is where the greatest growth is," explains Kaplan. As a result, ARBs are the fastest growing class of anti-hypertensive—growing at nearly 30% annually. ARBs had nearly 27% of the entire market in July this year, according to ABN Amro.

Anecdotal evidence suggests that physicians are increasingly prescribing the products first-line, too, given their improved side-effect profile (and equivalent efficacy) to ACE inhibitors.

Notwithstanding physicians' growing preference for ARBs, Novartis still has to work hard to distinguish valsartan from other ARBs. Although Takeda Pharmaceutical Co. Ltd./AstraZeneca PLC have been able, since September, to claim superiority over losartan in candesartan (Atacand)'s labeling, neither Novartis with valsartan nor Sanofi with irbesartan has approval to do the same, in regard to losartan or to each other.

Sums up Morgan Stanley analyst Andrew Baum, "there's not much difference between the actual molecules but Novartis has just done a terrific marketing job," in particular in the design and leverage of its trials. Merrill Lynch's Nigel Barnes agrees. "Diovan's success [in Europe and elsewhere] is almost entirely due to Novartis' having had an open check" for marketing and for the development on which this marketing is based, Barnes remarks.

New Niches

Novartis is pouring money into further carefully-designed clinical trials with valsartan (see Exhibit 2). Gaining approval for additional niche indications, such as congestive heart failure (CHF) or diabetes, is an important way to secure a competitive edge in the increasingly genericized hypertension market. Valsartan's approval in August 2002 for treating CHF among patients not taking ACEs—based on the 5000-patient ValHeFT study—means the Swiss group can now claim to have the first ARB to be approved in this indication, since Merck's losartan failed to show any benefit among severe heart failure patients in the 3000-strong ELITE II trial in 1999.

In this indication, too, the outcome—valsartan's success, losartan's failure—comes less from differences between the two ARB molecules, according to most analysts, than from trial design and subsequent marketing noise. The ELITE II trial pitted losartan against Bristol-Myers Squibb Co. 's ACE inhibitor captopril (Capoten). Novartis' Val-HeFT was a combination trial, comparing more than 5000 patients on valsartan as well as standard chronic HF therapies such as beta-blockers.

Points out Barnes, Val-HeFT showed "no benefit for valsartan in addition to standard treatments." It was only when given as a substitute for ACEs—in a tiny subsegment of the market—that benefits were seen. As a result, the market for which valsartan is approved in CHF is very small, but the added indication "helps perception," according to Barnes. And the noise generated by the approval in CHF "will endorse Diovan's use in its current indication."

Rising to the French Challenge

The French market has been particularly receptive to Novartis' global marketing efforts. France may not be Novartis' largest market, but with 18.7 million hypertensive patients in 2001, according to Datamonitor, and a rising incidence of the disease due to increased consumption of fatty foods, the French market is one of Europe's fastest growing.

It's also one of the most competitive. Besides losartan (still the leader in that market), home-ground player Sanofi-Synthélabo has been selling irbesartan in France since 1997 (the same year valsartan was launched there). Irbesartan and valsartan are head to head in market share terms, with just over 26% each in 2001 (see Exhibit 3); valsartan's share, however, includes sales of its partner Aventis SA , which co-markets the drug as Nisis. AstraZeneca/Takeda's candesartan (sold in France as Kenzen), Boehringer Ingelheim GMBH /GlaxoSmithKline PLC 's telmisartan (Micardis/Pritor) and Solvay SA 's eprosartan (Teveten) have also entered the fray. "There are a lot of strong, mature organizations in that [French] marketplace, with lots of reps behind them," points out Kaplan.

Yet the French physician community has been particularly receptive to Novartis' marketing style. French doctors like clinical-data—just what Novartis has focused on to back up its messages. Results from the VALUE trial won't be available until next year, but already, contends Kaplan, most French physicians see ARBs as the class-of-the-future in treating CV disease and hypertension.

Indeed, ARB uptake has been particularly quick in France—faster than in the US and other markets, according to Datamonitor. One reason for this is the compliance advantages that ARBs offer over other hypertension treatments—a particularly important issue to French doctors. Since hypertension is asymptomatic, patients are deterred from taking medication by even relatively minor side effects. As a result, non-compliance is one of the major reasons that so many treated patients fail to achieve target blood pressure goals, explains Christine Hollidge, an analyst at Datamonitor.

What's more, because generics are poorly penetrated in France, the downward price spiral seen among CCBs, ACE inhibitors and other older drug classes elsewhere will not be as steep there as in other countries, giving a smaller incentive for doctors to prescribe them in preference to ARBs.

The French affinity for ARBs, however, helps Novartis' competitors there too. This competitive pressure has forced Novartis' team to sharpen its differential detailing. Physicians aren't only segmented into Tareg-prescribers and non-Tareg prescribers, but also, at a drug class level, those who prefer—or don't prefer—ARBs to other drug types, particularly CCBs and ACE inhibitors.

Novartis' sales reps, for example, give doctors who hate ARBs and love ACEs a message about the key benefits of ARBs, whereas "those [doctors] who are already happily prescribing ARBs are told about the superior efficacy of this class and talk specifically about valsartan's characteristics," explains Novartis' Ebeling.

Based on different user groups (identified using historical prescribing data and other computerized information), Novartis' reps identify key selling messages for Novartis' own products, and key messages against the competition. "Our French team is definitely best [among Novartis' sales organizations] at using differential detailing," says Ebeling.

As a result, although valsartan hasn't overtaken Sanofi's irbesartan in France, it is providing stiff competition there—and is certainly on most cardiologists' radar screens. Irbesartan's recent approval for diabetic nephropathy—the first ARB to be approved in this indication—will ensure the battle continues.

Overall, though, valsartan is undoubtedly driving growth in the ARB class. The drug itself grew by nearly 23% in the year to July in Europe, and Morgan Stanley expects it will account for 10% of Novartis' total sales by 2005.

Novartis' global marketing strategy is the main engine behind valsartan's growth. But local tactics such as differential detailing can accentuate that growth in unique ways. And these practices needn't stay local; Novartis has successfully exported its differential detailing to other markets such as Spain. "Although businesses are ultimately local, when we have identified a good practice, we try to roll it out into other countries," sums up Ebeling.

—by Melanie Senior

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