Hypertension: excitement grows around Novartis hypertension franchise update in Big Apple

Despite almost 200 million people suffering from hypertension in the seven major pharmaceutical markets alone, according to a new report, innovation is scarce within antihypertensive R&D. What little innovation that does exist is being delivered by Novartis, which is set to launch two new antihypertensives in 2007 in the shape of oral renin inhibitor Rasilez, and the 'two-in-one' pill Exforge.

The eyes of all those with a vested interest in the antihypertensives market will be on the 21st annual meeting of the American Society of Hypertension (ASH) in New York, as Novartis is scheduled to present new clinical trial data on both products. Datamonitor believes this data could show significant benefits for patients with hypertension and boost each products' potential sales accordingly.

Hypertension...what's the big deal? 

According to recently published Datamonitor research, in 2005 the number of people with hypertension - defined as a blood pressure over 140/90mmHg - across the seven major markets reached 192 million, with this figure set to rise to over 210 million by 2015. 

On the back of this, sales of antihypertensive medications in 2005 reached $34.7 billion, up 4.8% on 2004 sales, with much of the value and growth in this market being delivered by the angiotensin-receptor blockers (ARBs), the last innovative class of antihypertensive drugs, which commanded nearly a third of the market with sales of just over $11 billion. 

While these patient numbers and the value of the market are compelling, it is important to bear in mind that the level of blood pressure and its reduction is essentially a 'surrogate end-point'. The primary aim in treating hypertension is the reduction of overall cardiovascular disease (CVD) and coronary heart disease (CHD) risk, for which blood pressure reduction is an evidence-based strategy. 

Weak pipeline, despite big market 

One would think that such a huge market would attract drug developers in their droves, with each attempting to get a slice of the action. The reality is, however, that the antihypertensives market is mature, with poor growth prospects due, in part, to a high level of genericization and a distinct lack of R&D innovation. A recent analysis of R&D activity within the antihypertensives market by Datamonitor has revealed a common trend among pharmaceutical developers; wring everything you can out of existing products.

With over 40% of current R&D projects looking to develop fixed-dose combinations (FDCs) of currently marketed antihypertensives, either with other approved therapies or with various new chemical entities (NCEs), low risk life-cycle management strategies are preferred over the higher risk, innovative strategies that seek newer, more effective ways of treating this disease. 

In Datamonitor's view, the lack of innovation and reliance on lifecycle management has been caused by two things. Firstly, sweeping cost-containment measures across many key markets have caused companies to re-appraise R&D efforts. For example, on the basis of the much publicized healthcare reforms in Germany, many German-based companies have threatened to withdraw R&D operations from the country due to R&D efforts not being rewarded. 

Secondly, and most importantly, scarce innovation could also be a reflection of the lack of novel targets and a belief that current treatments are as good as things are going to get, a belief shared by many industry experts and key opinion leaders. 

Innovation left to Novartis 

Since 1994, when the much-vaunted ARBs were introduced to the market as a revolution in the treatment of hypertension, very little innovation has been seen in the field of antihypertensive R&D. New approaches, such as Bristol-Myers Squibb's Vanlev (omapatrilat), a vasopeptidase inhibitor, failed to make it to market at the final hurdle due to an increased risk of debilitating side effects. 

Moreover, companies involved in developing and marketing antihypertensives have concentrated on the products they have, ensuring a maximal return on investment, rather than developing new, innovative treatments for the disease. 

However, with the expected launch of Rasilez (aliskiren), Novartis' first-generation orally active renin inhibitor in 2007, this is about to change. In collaboration with Speedel, Novartis is set to introduce the first innovative treatment for hypertension in over a decade. 

Comparative efficacy concerns aside, Rasilez has the potential to become an important option in the treatment of hypertension, particularly in resistant hypertensives and patients who require more than monotherapy to control their disease. It has thus far shown strong safety and efficacy, ARB-like tolerability and true '24-hour activity', providing Rasilez with the ability to control blood pressure overnight. This key differentiating factor for Rasilez should form a crucial element in Novartis' initial marketing campaign.

In-depth late-stage clinical trial data for Rasilez due to be presented at ASH 2006 this week should confirm Rasilez' potential, potential that Datamonitor believed Rasilez possessed in December 2005 despite a very bearish outlook from the Street. 

Initial uptake for Rasilez is expected to be good with first year sales of only $100 million rising to $1.4 billion by 2010. Moreover, the data presented at ASH 2006, and from the long-term outcome program for Rasilez expected in 2011, is expected to be positive and will accelerate sales from 2011 onward.

Beyond Rasilez 

With excitement surrounding Rasilez at an all-time high, Novartis' other pipeline antihypertensive Exforge, a FDC of the company's top-selling drug Diovan (valsartan) and the top-selling antihypertensive Norvasc (amlodipine), dipped under the radar until Novartis gave some top-line clinical trial data at an R&D day in January 2006. 

Like Rasilez, detailed late-phase clinical trial data for Exforge is scheduled for release at ASH 2006, with all eyes on in-depth data on the benefits of combining an ARB with a calcium-channel blocker (CCB). Early signs are that a combination of valsartan with amlodipine delivers excellent systolic (SDP) and diastolic blood pressure (DBP) lowering efficacy. Moreover, it seems that the incidence of edema, a common side-effect of CCBs, is reduced significantly by combining a CCB with an ARB and could potentially have a significant impact on patient compliance. 

In terms of market potential, Datamonitor believes Street estimates of $500 million annually are achievable, but stresses that Exforge, on the basis of reductions in blood pressure seen in late-stage clinical trials, could be limited to use in patients who have stage 2 hypertension (i.e. 160/110 mmHg), as defined by Chobanian et al (2003). 

According to an analysis of the US National Health and Nutrition Examination Survey (NHANES) data for 1999-2000, only 4.3% of hypertensives in the US are classified as stage 2. As such, should Exforge be limited to use in severe cases of hypertension, the market potential for Exforge may be limited. In essence, due to Exforge's efficacy, Novartis' patient potential may be limited.

Datamonitor will be publishing forecasts for Exforge during Q2 2006.

All eyes on the Big Apple 

So as the great and the good of hypertension research, development and marketing make their way to New York, Datamonitor believes that, while the program for ASH 2006 holds much to interest many, all eyes will be on Novartis as it updates the financial and medical communities on the company's new products, Rasilez and Exforge. 

With Novartis' top-selling antihypertensive, Diovan, bringing in $3.5 billion in 2005, according to IMS Midas Sales data, Novartis is seeking ways to shore up its cardiovascular and hypertension franchise as Diovan loses patent protection in 2012. By combining a well-harnessed lifecycle management strategy to its current franchise with cutting edge innovation, Novartis is set to become a hypertension powerhouse in the years to come.

Related research:

§          Pipeline Insight: Antihypertensives - Weak pipeline leaves innovation to Novartis priced $11,400

§          Commercial Insight: Antihypertensives - Two Years to Shape the Market? priced $15,200

§          Stakeholder Insight: Hypertension - Multiple Layers of Therapy Cover all Eventualities priced $15,200