Roche ends dalcetrapib trial, questions linger on CETP class

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A treatment Roche called a longshot has been left in the dust. The drugmaker announced Monday that it was ending tests of the drug dalcetrapib based on recommendations of an independent Data and Safety Monitoring Board which said the drug had a “lack of clinically meaningful efficacy” when it came to preventing heart attacks in patients with stable coronary heart disease who previously suffered clogged arteries.

Dalcetrapib, a CETP inhibitor, had already cleared two Phase IIb trials in August 2011, and Roche's decision in 2011 to start a second large Phase III trial helped fuel expectations. The drug worked by raising levels of HDL, or "good" cholesterol, a tack which the drugmaker thought could have a heart-protective effect.

However, Roche's attempt joins the trash heap along with Pfizer's torcetrapib, a molecular cousin of dalcetrapib which failed in 2006 due to safety issues. The Swiss firm said today that it's terminating the trial, called dal-OUTCOMES, and all the studies in its dal-HEART program.

Analysts have not derided today's outcome. “It has always been appreciated by the market that this was a higher-than-normal risk study, a point that Roche frequently reiterated,” Jefferies analyst Jeffrey Holford wrote in a research note.

That hadn't stopped blockbuster forecasts. By Holford's estimate, success could have brought in $1.4 billion in sales had dalcetrapib launched two years for now, and $5 billion at its peak. However, analysts say the loss isn't going to lower their company expectations, since most had no forecasts for CETP inhibitors in any of their company models.

But the news leaves analysts pondering the fate of this class. Roche was not the only drugmaker that saw hope in using HDL to protect the heart. Merck is currently exploring anacetrapib and Eli Lilly is looking into evacetrapib, which both function on the same principle: up HDL-cholesterol levels and reduce the risk of heart disease. Both Holford and ISI Group analyst Mark Schoenebaum say Roche's failure doesn't doom the category. “Merck's drug has far more profound impact on good and bad cholesterol than Roche's, and thus might still succeed,” Schoenebaum advised investors today.

The hope lies in the slightly different ways these other molecules may impact CETP. Bernstein Research's Tim Anderson wrote, "there is a 'bull case' to be made with anacetrapib because (a) it seems to lack the safety problems of torcetrapib, and (b) unlike dalcetrapib that only raised HDL cholesterol, Merck's product both raises HDL cholesterol and lowers LDL cholesterol. It is possible that the LDL lowering alone could carry anacetrapib across the finish line."

Holford noted that Merck and Lilly's contenders “provide significantly greater levels of HDL raising than dalcetrapib," around 3-4 fold more. ”Monday's announcement removes the only cardiometabolism drug [Roche] expected to file by 2013. The small molecule Aleglitazar is Roche's next cardiometabolic candidate, and the company expects to file an application with the FDA in three years, according to its website. Aleglitazar targets cardiovascular risk in type 2 diabetics.
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