Novartis pushes on with efforts to protect hypertension franchise

Analysis

Novartis announced data from two trials conducted with its core hypertension products at the American College of Cardiology meeting this week, Diovan and Tekturna. Both studies were part of the company’s huge ongoing attempt to protect this franchise from generic competition that is only going to intensify over the next few years and, unfortunately, neither generated positive data.

The studies were attempts to broaden these drugs’ use beyond hypertension, so a nice-to-have rather than a must-have. Much more important data from a huge clinical programme being conducted with Tekturna will start appearing later this year. Diovan sales probably peaked last year at just over $6bn and with patent protection lapsing in Europe at the end of 2011 and the US in 2012, Novartis is relying on Tekturna to keep it a significant player in the hypertension market. Analysts’ forecasts suggest opinions vary widely as to how successful the drug will be.

Generic erosion

The table below sets out Novartis’ hypertension franchise, illustrating how it is already expected to almost halve in value with the loss of mega-blockbuster Diovan. The extent of the decline largely depends on both the performance of Tekturna and how quickly Diovan is lost to generics.

Diovan is an angiotensin II receptor blocker (ARB), used to treat heart failure in patients who cannot tolerate ACE inhibitors.

ACE inhibitors, now widely available generically but previously a multibillion dollar class dominated by brands such as Servier’s Coversyl, Sanofi-Aventis’ Tritace and Merck & Co’s Vasotec, are still the most widely prescribed anti-hypertensive drugs. In fact, there is evidence that their use is still growing over ARBs like Diovan, Daiichi Sankyo’s Benicar and Boehringer Ingelheim’s Micardis which, due to remaining patent protection, are much more expensive.

The first major ARB, Merck & Co’s Cozaar, which sold $3.56bn last year, loses patent protection next month.

Novartis itself has admitted this will hit Diovan prescriptions and has said it will respond with rebates, as well as by diverting marketing efforts into other areas of its hypertension portfolio, which most notably includes Tekturna.

Protect and prolong

Tekturna, which Novartis gained full control of through the acquisition of Speedel in 2008, was bought largely in an attempt to extend the company’s hypertension franchise. Serious marketing money has been spent in the last couple of years, and Tekturna revenues in 2009 doubled largely as a result.

The table below shows that analysts see the product becoming a blockbuster itself by 2012, but these numbers mask vastly different opinions.

Morgan Stanley for example does not expect the product to ever become a billion-dollar seller, pencilling in peak sales of $645m for 2014, the same year that UBS has pencilled in sales of $2.34bn.

Clearly, banks will be taking different views about how resilient Tekturna itself is to the genericisation of the ARB class. The drugs work differently, ARBs targeting angiotensin II which causes blood vessels to tighten and narrow whilst Tekturna inhibits rennin, an enzyme produced by the kidneys that starts a process which leads to the formation of angiotensin II.

Additionally, a number of combination drugs have recently been launched or filed, including Valturna, a pill that combines Tekturna and Diovan, and a combination of Tekturna and amlodipine, Pfizer’s Norvasc and a Tekturna/amlodipine/diuretic triple combination. Opinions also differ on how successful these products will be; although one-pill combinations are more convenient price is increasingly becoming an issue in this area, even in the US.

But analysts could also be taking a view on how successful the Aspire Higher programme is likely to be in establishing Tekturna as a better product, or at least a worthy add-on to what will then be cheap generics.

Aspire higher

Around 35,000 patients are being recruited for 14 studies under the programme, several of which are outcome studies striving to establish a mortality benefit, something that could have a big impact on future sales. They are also seeking to establish a benefit in new, defined patient populations.

Key outcome studies include Accelerate in uncontrolled primary hypertension and Astronaut in acute heart failure, with data due in 2011; Altitude the following year in type II diabetes and then Atmosphere in chronic heart failure due in 2013. Apollo, in high risk elderly patients with normal blood pressure is also underway.

The study reported today was conducted in patients who had previously suffered a heart attack and were already on standard therapies; unfortunately adding Tekturna did not improve heart function for these patients. Novartis has decided not to pursue an outcome study in this group.

The study with Diovan, Navigator, was conducted in pre-diabetic patients who were on another Novartis drug, Starlix, and attempted to show whether the combination could delay progression to diabetes and reduce cardiovascular disease or risk factors. Over five years patients received a significant reduction in developing new-onset diabetes, but no reduction in the risk of cardiovascular events. Reviewers in the New England Journal of Medicine concluded that this combination was not worthy of use in clinical practise.

Clearly, the latter trial is disappointing, but in reality it is Tekturna that Novartis wants positive results from. With the combination pills hitting the market in the coming months and further data due from Aspire Higher, this topic is likely to become an increasingly common talking point for Novartis followers.

Novartis' hypertension franchise - marketed and late-stage pipeline WW annual sales ($m)
Status Product Generic Name Pharmacological Class Patent Expiry 2008 2010 2012 2014 CAGR (08 - 14)
 Marketed Diovan valsartan Angiotensin II antagonist 21-Sep-12 5,740 5,854 3,873 1,852 (17%)
Tekturna/Rasilez aliskiren hemifumarate Renin inhibitor 21-Jul-18 144 575 1,137 1,597 49%
Exforge amlodipine & valsartan Angiotensin II antagonist & calcium antagonist 21-Sep-12 406 771 853 363 (2%)
Lotrel amlodipine besylate & benazepril hydrochloride ACE inhibitor & calcium antagonist 18-May-07 386 187 123 97 (21%)
DynaCirc/Lomir isradipine Calcium antagonist - 84 74 76 78 (1%)
 Approved Valturna aliskiren & valsartan Angiotensin II antagonist & renin inhibitor 21-Jul-18 - - - - -
Filed Rasilez amlo aliskiren & amlodipine Renin inhibitor - - - - - -
Phase III LCZ696 - Angiotensin II antagonist & NEP inhibitor - - - - - -
Rasilez amlo HCT aliskiren, amlodipine & hydrochlorothiazide Renin inhibitor - - - - - -
Phase II SPP635 - Renin inhibitor - - - - 100 n/a
LCI699 - Aldosterone synthase inhibitor - - - - - -
Total franchise sales 6,760 7,460 6,063 4,087 (8%)
Total Novartis Group Prescription Sales 34,462 41,129 44,913 45,525 5%
% hypertension franchise 20% 18% 13% 9%

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