Antidyslipidemics: market set for contraction as generics hit hard

London Wednesday October 4 2006 – 

At the end of 2005 the antidyslipidemics market was worth a staggering $27 billion*, with the statin class commanding over 85% of the market. The reasons for the statins’ dominance are several-fold, but centre largely on aggressive, multi-channel marketing of statins by ‘big pharma’ companies. However, according to a new report from independent market analyst Datamonitor**, the winds of change are set to blow through the antidyslipidemics market. Between 2006-15, three high profile branded statin patent expiries – Zocor and Pravachol in 2006 and Lipitor in 2011 – are expected to wipe $14 billion off the value of the market. Combined with the fact that pipeline products are not expected to make up the difference, the antidyslipidemics market is on the verge of significant contraction.

Dyslipidemia; a brief overview?

Dyslipidemia is a disorder of lipid metabolism. This term is often used as a blanket term for any imbalance in the level of blood lipids. As such, it is often used to describe a variety of conditions characterized by either excessively high or excessively low levels of certain lipids in the bloodstream, such as cholesterol and triglycerides. The main cholesterol carrier is low density lipoprotein cholesterol (LDL-C; sometimes called “bad” cholesterol) and there is much evidence to suggest a direct relationship between levels of LDL-C and rates of coronary heart disease.

As such, much of the current therapeutic focus is on reducing levels of LDL-C, explains Datamonitor’s senior healthcare analyst, Dr Duncan Emerton. “There now exists a huge body of evidence to show the clinical benefits of reducing LDL-C via pharmacotherapeutic intervention. Since 1994, when the statin era began with the publication of the 4S study1, aggressively treating elevated LDL-C has become the cornerstone of antidyslipidemic therapy due to significant improvements in cardiovascular outcomes. However, the war is far from won.”

Statins have brought us a long way, but not all the way

Despite the introduction of the statins, by far the most effective LDL-C reducing therapy on the market, there is still a lot left to do in preventing cardiovascular events such as heart attacks and strokes. Dr Emerton says: “the most effective reduction in cholesterol using statins in a recent meta-analysis2 was about 1.7mmol/l, which was associated with a 38% reduction in coronary events like heart attacks. However, what this really means is that 62% of patients still had a major coronary event, suggesting that statins have brought us a long way, but there is still some distance to travel.”

When combined with the fact that most of the statins are marketed by cardiovascular kingpins such as Pfizer and Merck, its not difficult to understand why the statins were the dominant class of antidyslipidemics across all major markets in 2005. “To put this dominance into perspective”,

Dr Emerton says, “at the end of 2005, the antidyslipidemics market* was worth $27 billion, of which, 85% was generated by the statins. Additionally, Pfizer’s Lipitor (atorvastatin) alone commanded 40% of the entire antidyslipidemics market with sales of $10.6 billion. As I explained previously, robust clinical trial data plays a part in this success. However, I believe that aggressive, multi-channel marketing by big pharma is the key reason for such overwhelming commercial success.”

The statins dominate, but for how long?

Historical dominance aside, future trends in the antidyslipidemics market are expected to change significantly as a result of high profile generic entrants into the market. In 2006 Merck’s Zocor (simvastatin) and Bristol Myers Squibb’s (BMS) Pravachol (pravastatin) both lost US patent protection, an event that is expected to mark a turning point in the global value of the antidyslipidemics market, Dr Emerton says. “2006 is likely to mark an inflexion point in the sales value of the statin class across the seven major markets as a decline in the class’s dominance begins.

Generic erosion of Zocor and Pravachol revenues in the US are forecast to wipe $8 billion off the sales branded statin monotherapy in the US market in the five years between 2006-11 alone.”

Moreover, a more long-term threat to the dominance of the statin market is expected to hit hard in 2011, when Pfizer’s Lipitor begins to lose patent protection in several major markets. In addition to the impact of generic simvastatin and pravastatin, a further $6 billion is likely to be lost when Lipitor begins to lose patent protection in 2011. With the US statin sales accounting for just over 60% of total antidyslipidemic sales*, these events are expected to have an impact on global market value; evidence that US trends significantly impact global market movements,” he says.

What of the future in antidyslipidemic therapy?

Strategies designed to limit the impact of generic erosion on lipid management franchises include the development and commercialization of novel products. With further advances in LDL-C lowering efficacy unlikely without reductions in patient safety, current research is focused on developing better tolerated and more effective HDL-C targeted therapies. “Pfizer’s CETP inhibitor, torcetrapib, is a good example of this new approach”, Dr Emerton says. “The compound has promising Phase II data in combination with Lipitor, but some concerns exist regarding torcetrapib’s pro-hypertensive side effects. Additionally, with a recent commitment from Pfizer that the company would sell torcetrapib as a monotherapy3, Pfizer is poised to execute a highly successful launch of a torcetrapib/atorvastatin combo pill in the first instance, followed by the launch of the monotherapy at a later date.”

In addition to torcetrapib, other HDL-C targeted therapies in development include the Apo-A1 mimetics. Two such projects include Pfizer’s ETC-216 (apo A-1 Milano) and Novartis’s APP018, both of which were acquired from smaller companies, namely Esperion and Bruin Pharmaceuticals, respectively.

Due to ETC-216’s injectable formulation, Dr Emerton predicts that Novartis’s APP018, which can be taken orally, will be a huge commercial success. “Despite only being in Phase I trials and about 6-8 years from seeing a pharmacy shelf, APP018 has the potential to be a huge product for Novartis, and will build upon the company’s strong cardiovascular heritage.”

“Early animal data for APP018 is exciting as not only have we seen excellent HDL-C elevating efficacy, APP018 has been shown to reduce the amount of atherosclerotic build-up in diseased vessels; the Holy Grail of lipid management and anti-atherosclerotic R&D.”

What these deals illustrate is a growing trend in lipid management and anti-atherosclerotic R&D; big pharma willing to pay top dollar for companies and products in the short-term should the longer-term return on investment be sufficiently great, Dr Emerton says. “R&D productivity within the pharma industry has been the subject of much debate over the last 3-5 years, as the number of new products emerging from big pharma has fallen due to issues of internal R&D productivity. What these deals show is that big pharma who are active in the lipid management market are not immune to such trends and are willing to pay huge sums for products that have shown potential.”

“For example, Novartis paid $200m for APP018 and it was barely out of the lab. However, this will seem like small change compared to the billions of dollars Novartis, and other companies like Novartis, will be able to generate from these next generation antidyslipidemic products.”

Notes

*across the seven major markets: UK , US, France , Germany , Italy , Japan and Spain

**Commercial Insight: Antidyslipidemics - Branded statins beware, generics are amongst you

References

1.         Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4,444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994; 344: 1383–1389.

2.         Cholesterol Treatment Trialists’ (CTT) Collaborators. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005; 366: 1267–1278.

3.         Heart pill to be sold by itself. New York Times; 26 July 2006

Datamonitor’s (DTM.L) report Commercial Insight: Antidyslipidemics - Branded statins beware, generics are amongst you, provides analysis of the current status and future potential of the marketed antidyslipidemic drug classes across the seven major markets. Covers the statins, fibrates, ion-exchange resins, fixed-dose combinations, and cross-risk factor products.

  (4/10/06)