Doubling up in battle to beat cholesterol

London Tuesday August 23, 2005- Dyslipidemia, or high blood cholesterol is one of the most prevalent conditions in the western world, with over 266 million suffers in the seven major pharmaceutical markets- more than twice the population of Japan. Furthermore, according to a new report from independent market analyst Datamonitor* (DTM.L), the diagnosed population is expected to increase in the years to come, especially now that updated guidelines have lowered the threshold further and more people need to be treated. The rise in obesity and type 2 diabetes and the increased awareness of metabolic syndrome is also expected to drive both awareness and significantly increase the number of people diagnosed. Fortunately, due to the large patient pool, there is no shortage of drug manufacturers willing to invest in the market, which already boosts the best selling pharmaceutical product in the world.

Variety of conditions

Dyslipidemia is a disorder of lipid metabolism. This term is often used as a blanket term to describe any imbalance in the level of blood lipids, thus, it is often used to describe a variety of conditions characterized by either excessively high and excessively low levels of certain lipids in the bloodstream. These lipids include cholesterol, cholesterol esters, phospholipids and triglycerides.

In terms of total prevalence, it is a disease of middle age, with the peak in men occurring between 35 and 55 years of age and between 55 and 65 years of age in women. Lipid levels are relatively high in juveniles under the age of 14, but this is generally not considered a risk in the same way as for adults. Prevalence then rises rapidly into middle age, peaking around 45 years of age for men, whilst continuing to climb for women to around age 60. One of the reasons for this delayed rise in dyslipidemia in women is that estrogen provides a degree of natural protection against coronary atherosclerosis before menopause, according to Datamonitor cardiovascular analysts Jasjeet Mohain. “Combined with the greater life expectancy in women, this leads to the visible difference between men and women in the ages for peak prevalence of dyslipidemia,” she says.

Biggest of big guns

Pfizer’s Lipitor is the most widely used treatment for lowering cholesterol and the best-selling pharmaceutical product of any kind in the world. In fact in 2004, Lipitor became the pharmaceutical industry’s first $10 billion product. It holds approximately 40% of the worldwide sales in the lipid-lowering market and more than 42% of the US market in total prescriptions and continues to post strong growth (18% growth in 2003–04) around the world (1).

However the two leading product in Pfizer’s cardiovascular portfolio- Lipitor and Norvasc- are at risk of generic erosion, with Norvasc losing patient as early as 2007. Lipitor loses its key product patient in the US in 2010 and potentially as early as 2007 in Europe, Mohain says. “Hence it is unsurprising that Pfizer is keen to protect sales of Lipitor, as well as maintain a strong cardiovascular portfolio. Datamonitor has identified at least 16 drugs in Pfizer’s developmental pipeline for the indication of dyslipidemia alone- including preclinical drugs.”

In order to protect the large amount of its revenue that is derived from its cardiovascular portfolio, Pfizer has decided to develop torcetrapib (the first in the cholesteryl ester transfer protein (CETP) class) only in combination with atorvastatin, causing outrage to many physicians. As this product will only be marketed in combination with atorvastatin, it prevents torcetrapib from being used with any other statin or with generic atorvastatin (when it becomes available). Pfizer has designed a thorough and extensive Phase III clinical trial which plans to enroll 25,000 patients. However there will be no clinical trial information on how torcetrapib performs in combination with any therapy other than Lipitor, leaving those who are unable to tolerate (or afford) Lipitor without a way to obtain torcetrapib for use with another statin that may suit them better, Mohain says.

“However Pfizer argue that it is not feasible for any one provider to fund studies of torcetrapib in combination with all the currently available statins. The development of the atorvastatin and torcetrapib combination alone will cost Pfizer $800m.”

In clinical trials torcetrapib in combination with atorvastatin has been shown to increase HDL (‘good’ cholesterol) levels by 55%—significantly more than any other compound that is currently on the market. It also decreased LDL (‘bad’ cholesterol) by 17%. This LDL lowering was beyond the LDL reductions seen during the placebo phase of the study when patients received atorvastatin only (2).

It also appears to be more potent than currently available combinations such as Advicor and the pipeline drug KS-01-019 (simvastatin + Niaspan) which are plagued by the flushing side effect of Niaspan. And due to Pfizer’s strong marketing capabilities Datamonitor sees this combination as the most promising in the pipeline. Thus, Pfizer’s atorvastatin + torcetrapib combination is forecast to reach sales of $4,321 billion by 2015.

Adjunctive therapy the way forward?

Datamonitor forecasts Japanese Tobacco/Roche’s JTT-705 (a CETP inhibitor) to become the second most successful drug in the pipeline, with sales of $674m by 2015, Mohain says. “JTT-705 has a great potential as an adjunctive (combination) therapy as physicians will be able to prescribe it to patients receiving any statin. The value of a statin/CETP-inhibitor combination therapy would allow a dual approach to lipid-profile management and acknowledges the fact that physicians have increasingly come to view reduced HDL cholesterol as a risk factor comparable in importance with increased LDL cholesterol.”

In fact there appears to be a lot of investment in adjunctive therapies throughout the antidyslipidemic pipeline, with approximately 69% of the drugs in the pipeline being trialed as adjuncts. However the pipeline is still relatively young, with 91% of drugs in either Phase I or II.

The pipeline is dominated by the peroxisome proliferators-activated receptor (PPAR) class, with a total of nine in development out of the 44 products. With the dyslipidemia market already saturated with third-generation statins, finding a superior therapy is likely to be difficult, Mohain says. “However the possible improvement with drug classes such as PPAR alpha agonists could expand the adjunctive market. This potential is set to increase by the fact that the number of patients with mixed dyslipidemia and diabetes is increasing, which is expanding the patient population,” she says.     

Ends

Notes for editors
* Pipeline Insight: Antidyslipidemics - The Power of Two

(1)Pfizer’s financial report 2004
(2)Brousseau et al., 2004

Datamonitor’s report Pipeline Insight: Antidyslipidemics - The Power of Two, is an in-depth, critical evaluation of compounds in development for dyslipidemia. It assesses the commercial prospects for the launch of innovative new products against the level of existing unmet needs, and provides event and sales forecasts to 2015.

Click title to purchase Pipeline Insight: Antidyslipidemics - The Power of Two

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