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The previous generation of statin treatments, although extremely profitable, had plenty of problems. Statins like Pfizer's (NYSE: PFE ) Lipitor, Merck's (NYSE: MRK ) Zocor, and AstraZeneca's Crestor were effective at reducing levels of LDL ("bad") cholesterol, but they also had some pretty bad side effects, including liver, muscle, and nerve damage, digestive problems, memory loss, and an increased risk of developing type 2 diabetes.
Nevertheless, statins have been some of the best-selling drugs over the past decade. Pfizer's Lipitor generated peak sales of $13 billion in 2011 and became the top-selling drug of all time. However, that heyday couldn't last forever -- Zocor and Lipitor's patents expired in 2006 and 2011, respectively, and generic statins flooded the market.
However, a new class of cholesterol drugs, known as PCSK9 inhibitors, have arrived, led by Sanofi, Regeneron, and Amgen.
PCSK9 is an enzyme that binds to the liver's LDL receptors and degrades them, ultimately limiting the liver's ability to lower LDL cholesterol levels. PCSK9 inhibitors attempt to keep the enzyme from binding to LDL receptors.
Statins, by comparison, target the HMG-CoA enzyme in the liver to inhibit the production of LDL cholesterol. However, this can be counterproductive, since statins have been found to actually stimulate the production of PCSK9, ultimately throttling the liver's ability to naturally lower LDL cholesterol levels.
Sanofi and Regeneron's alirocumab
Sanofi and Regeneron's PCSK9 inhibitor, alirocumab, is the current leader in this new class of drugs.
Last month, Sanofi and Regeneron reported positive phase 3 results for the drug in tests against Merck's Zetia, a drug that decreases the absorption of cholesterol in the small intestine.
Patients given alirocumab showed a 47.2% reduction in LDL levels, compared to a 15.6% reduction in the Zetia group. However, it should be noted that although Zetia can be taken alone, it is often combined with statin treatments. Merck's other cholesterol drug, Vytorin, is actually a combination of Zetia and Zocor.
The most common side effects reported by patients from alirocumab monotherapy included the common cold, influenza, and respiratory infections. Sanofi and Regeneron are expected to release more detailed top-line results from the phase 3 trial in early 2014.
If approved, alirocumab would be a big step for both Sanofi and Regeneron. Sanofi currently relies heavily on the continued growth of its diabetes treatments and rare diseases unit, Genzyme. Meanwhile, Regeneron is highly dependent on its eye disease treatment Eylea, which accounted for 61% of its total revenue last quarter.
If approved, alirocumab could hit peak annual sales of $3.5 billion, helping diversify the drug portfolios at both companies.
Amgen's AMG 145 is catching up quickly
Amgen is not that far behind Sanofi and Regeneron with its PCSK9 inhibitor, AMG 145. On Nov. 19, Amgen reported that the drug reduced LDL levels by 52% after a year with no serious increase in adverse events during a phase 2 trial.
However, the trial cannot be directly compared to Sanofi and Regeneron's, since Amgen's study compared patients receiving AMG 145 with statins to a second group that only received standard treatments.
In addition, Sanofi and Regeneron's aforementioned monotherapy trial only tested their drug on 103 patients, while Amgen tested its drug along with statins on a much larger group of 1,104 patients. Sanofi and Regeneron are also testing alirocumab on a much larger group of 18,000 patients in conjunction with other lipid-lowering therapies.
Eventual market approval for AMG 145 could be a major step in decreasing Amgen's dependence on Enbrel, the blockbuster arthritis treatment that accounted for 25% of its revenue last quarter.
Peak sales estimates for AMG 145 run as high as $4 billion -- which would come close to matching the $4.2 billion in sales that Enbrel generated last year.
Could RN-316 be Pfizer's next blockbuster?
Last but not least, Pfizer is looking to get back into the cholesterol treatment market with its own PCSK9 inhibitor, RN-316.
RN-316 is in phase 3 trials, and Pfizer has outlined some ambitious plans for the treatment -- it is testing the drug on lowering LDL levels, as well as its impact on cardiovascular health. Pfizer's test group is even bigger than Sanofi and Regeneron's, at 22,000 patients, and tests RN-316 on patients with a wide variety of cholesterol levels.
Pfizer's study has two main stages -- the first study will see if RN-316 can help patients whose levels of LDL cholesterol cannot be effectively reduced by statins alone. The second study will attempt to reduce LDL cholesterol to levels lower than competing treatments.
There haven't been any peak sales estimates for RN-316 yet, due to the lack of concrete trial data, but it's likely that sales projections will come close to those for alirocumab and AMG 145.
Pfizer clearly believes that RN-316 could be its ticket back into the cholesterol treatment market, which could be a positive catalyst for the company, considering that its former top-selling statin Lipitor only generated $533 million in revenue last quarter -- a 29% drop from the prior-year quarter.
The Foolish takeaway
Although PCSK9 inhibitors are promising new treatments for high cholesterol, let's not get ahead of ourselves. These new treatments won't completely replace statins, at least not right away.
If approved, they will initially be prescribed to patients who cannot tolerate statins. For other patients, PCSK9 inhibitors will also prescribed along with statins, rather than as a monotherapy. There are also troubling concerns that when combined with statins, PCSK9 inhibitors could actually lower cholesterol levels too much and cause other health problems.
Yet there's still plenty of excitement for PCSK9 treatments, fueled by blockbuster peak sales projections from analysts. However, investors shouldn't simply expect these PCSK9 treatments to immediately become the next Lipitor. Instead, they should study the long-term growth potential of these treatments and if they can actually stand alone as a replacement for statins.
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