As the race heats up to develop a combination cholesterol therapy that will lower low-density and raise high-density lipid levels, a new deal gives Abbot Laboratories and AstraZeneca two promising candidates.
The two companies want to combine one of Abbott's fibrate compounds with Crestor (rosuvastatin), a statin made by AstraZeneca. Fibrates raise HDL levels and lower triglycerides.
The two Abbott compounds proposed for the single-pill therapy are TriCor (fenofibrate), which is already on the market, and ABT-335, which is in Phase III clinical trials.
"It's a big opportunity for us," said Eugene Sun, MD, vice president of global pharmaceutical development. "I think this gives us a step into the larger space."
The new combination therapy would compete with Pfizer's proposed combination of Lipitor (atorvastatin) with torcetrapib, an HDL-raising drug also in Phase-III clinical trials. Many analysts see the move as part of a larger strategy to extend Lipitor's patent life.
Meanwhile, Merck is testing Zocor (simvastatin) with an experimental compound that might increase HDL levels and decrease triglycerides. Kos recently launched Advicor, a combination of Niaspan (niacin) and lovastatin, and is also testing a Niaspan/simvastatin combination.
"I think statins are going to be the cornerstone of cholesterol treatment," said Peter Jones, MD, a consultant for Abbott who is an associate professor of medicine at Baylor College of Medicine. "[But] the real future of preventing cardiovascular disease is combination therapy."
Of Abbott's two fibrates, ABT-335 might be more bioavailable than TriCor, meaning it could be given at a lower dose, Jones said.
Abbott is testing both compounds in combination with Crestor but will ultimately select only one for the combination pill.
Abbott had considered other statins for a one-pill therapy, and the company will test TriCor as a co-administered therapy with other LDL-lowers. But Sun noted that the physical properties of Crestor might make it more complementary in a single pill.
"Crestor is a very powerful statin," Sun said. "Gram for gram, it has more LDL-lowering capacities."
Abbott will test its fibrates with the 5, 10, and 20 mg doses of Crestor, not the high doses that have been linked to muscle and kidney side effects.
"At the doses Crestor is being used, it has the same safety profile as some of the other statins," Sun said.
A study presented at November's American Heart Association meeting found that TriCor alone reduced microvascular complications from diabetes even though it did not meet its primary endpoint of preventing fatal heart attacks. Since TriCor might have greater benefits when combined with a statin, the AstraZeneca deal may allow Abbott to move into related markets, such as diabetes.
Abbott completed its acquisition of Guidant's vascular business in April, and is hoping to become a stronger player in the cardiovascular market. The therapy similarly helps build AstraZeneca's diabetes franchise.
Prescribing fibrates with statins is already a common treatment for patients with dyslipidemia, says James Blassetto, MD, executive director of strategic development at AstraZeneca. "It actually is felt to be a growing population," Blassetto said.
Under the proposed terms of the deal, AstraZeneca will hold the NDA on the new compound while Abbott will conduct the clinical trials and be responsible for regulatory registration. The companies will co-market the product, pending approval. They forecast a 2009 FDA submission.