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 givesAbbot 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 inPhase 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.

Articles

Deal combines Crestor with either TriCor or experimental fibrate.

Abbott, AstraZeneca Join Race to Develop Combo Cholesterol Drug

A miniscule number of physicians--less than half a percent--have opted to restrict their prescribing data from drug sales reps.

As of yesterday, about 2,900 of the nation's 800,000 practicing physicians had enrolled in the American Medical Association's (AMA) prescribing data restriction program (PDRP). The program went into effect July 1, but physicians could sign up as early as May.

Robert Musacchio, senior vice president of publishing and business services at the AMA, called the initial numbers "pretty substantial."

He expects to see an increase in the enrollment rate, but said the level of interest will depend on how physicians view their interactions with sales reps. "Just giving them an option [to opt-out] alleviates their concerns," he said.

Another explanation: Physicians don't know enough about the program yet.

Maritz Research last month polled 118 primary care physicians and 100 specialists about the PDRP. The results showed that while only 18 percent were aware of the program, 53 percent were interested in signing up.

Writing directly to physicians does not work, said AMA spokesman Robert Mills. The group's research shows that physicians don't open AMA mail.

The AMA is instead trying to raise awareness through articles in medical journals and interviews in major newspapers. "I know we've done everything to get the message out," Musacchio said.

About half of respondents in Maritz's poll said that it is appropriate for companies to use prescribing data to prepare patient education materials or provide drug samples. About 21 percent saw no problem with using the data for sales and marketing activities.

Similarly, the AMA reported that a small number of physicians--fewer than five--have rescinded their enrollment in the PDRP once they realized the implications.

"I actually thought these were good numbers; these were numbers pharma should be leveraging," said Madhunika Raghavan, who heads the pharma group at Maritz Research. "Physicians need to know pharmaceutical companies use this data for a number of non-marketing purposes."

As part of a pilot program in California, physicians who choose not to enroll in the PDRP will be able to access their own prescribing data as well as comparative data and educational material on prescribing for common diseases. "Not only is it an opt-out program, but we're also providing physicians with information," Musacchio said.

The day before the PDRP launched, New Hampshire became the first state to ban the sale or use of prescription data for marketing purposes.

Despite their similarities, the AMA measure is considered to be more industry-friendly than the New Hampshire law. In fact, a position paper from AMA stated that it is "troubled" by state measures such as New Hampshire's, and noted that sharing individual prescribing data does not compromise patient confidentiality.

PhRMA too offered its tentative support to the PDRP, but added that it is too soon to gauge its full effect.

The PDRP still allows drug company executives to maintain access to prescribing data--as long as they don't share it with their sales force, noted Ken Johnson, a PhRMA senior vice president, in a statement.

"Unlike the New Hampshire law . . . the AMA project allows important aggregate information to be made available for important health quality efforts," Johnson said.

Some observers believe that the AMA effort might forestall state legislation.

"The PDRP is a lot less restrictive than state legislation," Raghavan said. "I think a lot of the concern right now is whether this is a sign of things to come."

"There are a lot of states in a holding pattern," said Jim Alonso, chairman and CEO at ASI Business Solutions, which makes compliance software. "[New Hampshire] is the first domino that has fallen."

AMA says enrollment depends on physicians' experiences with drug reps.

Pharmaceutical Executive-07-19-2006

Abbott, AstraZeneca Join Race to Develop Combo Cholesterol Drug

Small Percentage of Physicians Enroll in PDRP