Risky Cholesterol Drug Proves Positive for Roche

With all the negative news about Vytorin coming out of the American College of Cardiology's (ACC) annual conference this week, it has been easy to overlook some of the positive developments.

Such as? Roche's announcement that its anti-cholesterol drug, R1658, showed positive safety data in short-term Phase II trials. According to a statement sent to Pharm Exec, "R1658 does not show any drug-related increase in adverse events. Results also showed that R1658 raised HDL- C and exhibited potentially favorable effects on other lipid parameters."

Developed jointly by Roche and Japan Tobacco, R1658 is a cholesteryl ester transfer protein (CETP) inhibitor—a novel class designed to boost high-density lipoprotein (HDL) cholesterol levels and cut the formation of arterial plaque and the risk of cardiovascular disease.

Not Your Pfizer's CETP Inhibitor
The Roche data are being eagerly eyed because it remains to be seen whether the mechanism of action can work as designed. The first CETP inhibitor, Pfizer's blockbuster-to-be torcetrapib, had to be canned in late 2006 for causing more deaths than placebo in two large, Phase III trials. But Roche claims that R1658 shows no effect on blood pressure or activation of renin angiotensin aldosterone (the system involved in blood pressure control)—which doomed its older brother.

Still, the clinical trials cited at ACC only lasted for four or 12 weeks—nowhere near long enough to properly gauge safety issues for a drug that will be taken daily for years by millions of people. Roche said that the most common side effects observed in these test runs included headaches and gastrointestinal disorders. The drug has yet to go head to head against other anti-cholesterol drugs.

"These results are encouraging and show that, based on Phase II results, the compound does not appear to exhibit adverse cardiovascular effects or adverse effects on blood pressure when compared to placebo," stated lead author, George Steiner, Department of Medicine, Toronto General Hospital, Canada. "We will await future results with interest to see if R1658 has the potential to reduce morbidity and mortality in patients with cardiovascular disease and, at the same time, is without significant safety concerns."

Raise High the HDL—and the Hurdles
Michael Latuis, corporate analyst at Decision Resources, said that the drug is being watched very closely and that the HDL-raising market remains an appealing target market to go after.

"The Pfizer problem definitely caused people to stop and take a closer look at these drugs—and extended the time frame for Roche to be able to bring this product to market," Latuis told Pharm Exec. "But based on the data we have seen, we do think it will make it to market around 2013."

R1658 is now headed into Phase III clinical trials for a cardiovascular outcomes study with 15,000 patients. "The Phase III trials will need to be long and extensive to clear FDA's hurdles on this one," Latuis said.