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Roche Seeks Win on Heart Pill Where Pfizer Failed

By Naomi Kresge - Aug 19, 2011

Roche Holding AG (ROG) may get the first signs at a cardiology conference this month that the Swiss drugmaker can garner $6.8 billion in sales with a pill to combat heart disease by raising so-called good cholesterol.

The drug, dalcetrapib, may reap that much in annual revenue by 2020 if it works in patients who have had heart attacks, estimates Gbola Amusa, a UBS AG analyst in London. He gives the pill a one-in-four chance of succeeding.

That’s by no means a sure thing. Basel, Switzerland-based Roche, known for cancer medicines such as Avastin and Herceptin, is venturing into a new area. The basic concept was dealt a setback in May when a study found an Abbott Laboratories (ABT) drug to raise good cholesterol didn’t prevent heart attacks. Pfizer Inc. (PFE) had to scrap its version in 2006 after patients died.

“There’s excitement,” said Chris Cannon, a cardiologist at Brigham and Women’s Hospital in Boston, in a telephone interview. “We’ve been thinking about this for decades. On the other hand, there’s renewed caution and realization that it’s hard to make things work.”

Roche will present results at the European Society of Cardiology conference in Paris from a pair of trials that look at the drug’s effect on blood vessel function and see whether it can shrink artery-clogging plaque.

Called dal-Vessel and dal-Plaque, respectively, the two trials won’t answer the more pressing question of whether Roche’s drug helps keep patients alive and blocks heart attacks and strokes, Cannon said. That’s being addressed in a bigger study known as dal-Outcomes.

Results in 2012

Interim results from the 15,800-patient trial are expected early next year, with a first set of final results by December 2012, Pascal Soriot, Roche’s pharmaceutical unit head, said in a conference call with analysts on July 21.

Still, Cannon said, “if plaque shrinks, that is a huge win and very exciting, and everyone is going to be jumping up and down saying, ‘Hurray, this class works.’” An abstract of data for the dal-Plaque study is scheduled to be posted on the conference website tomorrow. Dal-Vessel is due to be presented in an oral session on Aug. 28.

Eli Lilly & Co. (LLY), based in Indianapolis, and Merck & Co. of New York have similar drugs in development aimed at increasing good cholesterol, or HDL, in the bloodstream.

HDL flushes fat deposits from arteries to the liver to be eliminated from the body. By contrast, statins such as simvastatin and Pfizer’s Lipitor, the best-selling drug in the world, decrease levels of bad cholesterol, or LDL, which blocks arteries and leads to heart attacks.

Multiple Blockbusters

If both smaller Roche dalcetrapib trials are successful, they could increase the probability of success in the larger study, UBS’s Amusa said in a telephone interview. If the best case occurs, and HDL-raising drugs prove as successful as statins in larger studies, the market could rival the size of that for cholesterol-lowering medicines and produce multiple drugs with sales of more than $1 billion a year, he said.

“It’s very difficult for this drug to be anything but either an outright failure or a mega-blockbuster,” he said. He has a “neutral” rating on Roche’s shares. Peak sales may be higher than his forecast if the medicine sees use in the bigger pool of high-risk patients who haven’t had a heart attack yet, Amusa said.

Interest is higher in this month’s results from the smaller trials because of the Pfizer history, Roche Chief Executive Officer Severin Schwan said in an interview at the company’s headquarters in July.

‘Rewriting the Textbooks’

“It’s a high-risk project, because what we want to know is that HDL has a positive effect,” Schwan said. “Nobody has proven this yet. I always say dalcetrapib is the biggest proof- of-concept study we ever did.”

In a conference call with analysts in 2010, Schwan said the drug had the potential of “rewriting the textbooks in cardiovascular medicine” and named the pill among a group of medicines with potential for more than 5 billion francs ($6.3 billion) in sales, according to the call transcript. He declined in July to elaborate on the sales potential for the drug.

Roche may have good reason to be cautious. Pfizer abandoned its pill to raise HDL, torcetrapib, five years ago after it unexpectedly raised increased death rates even as it raised levels of good cholesterol. The New York drugmaker had invested $1 billion in the drug to stem the loss of revenue when Lipitor loses patent protection this year. Since then Pfizer has cut jobs, closed research labs and bought Wyeth for $68 billion in 2009 to help plug the gap to be left by Lipitor.

‘Real Concern’

Roche decided to continue with dalcetrapib after Pfizer’s failure because of experiments showing the two drugs don’t work the same way and don’t share the same toxicity, Alexander Klauser, a spokesman for Roche, said in an e-mail.

“Step one with your drug is to make sure it doesn’t kill anyone, and with this class, given the experience with torcetrapib, safety’s been a real concern,” said Jack Scannell, a London-based analyst for Sanford C. Bernstein Ltd.

Meanwhile, in May the National Institutes of Health stopped a study of another HDL-raising drug, Abbott’s Niaspan, after it was linked to strokes and failed to reduce heart attacks. Niaspan works to raise good cholesterol in a different way than the Roche and Merck drugs, and it has different side effects, said Graeme Green, a London-based analyst for Decision Resources, in a telephone interview.

Roche helped alleviate some concerns by saying in July that the Outcomes trial had continued after an initial interim safety analysis had been completed, Bernstein’s Scannell said. He rates Roche shares “market perform.”

Merck’s Drug

Cannon, the Brigham and Women’s cardiologist, agreed. The dalcetrapib trial set some safety concerns to rest by progressing further than Illuminate, the torcetrapib trial Pfizer had to abandon in 2006, he said. Cannon is involved in studies of Merck’s good-cholesterol pill anacetrapib.

A study presented in November at the American Heart Association meeting in Chicago showed the Merck drug raised HDL, lowered LDL and left patients with fewer heart complications. The study numbers were small though, with just 1,623 patients.

Doctors have “great hope, but we simply have to wait and see what the trials show,” Cannon said.

Many drugs have looked good in earlier trials and then failed in the final studies needed to get approval, said Steven Nissen, the Cleveland Clinic head of cardiology who helped test Pfizer’s unsuccessful good-cholesterol pill.

“The graveyard of drugs is littered with examples,” said Nissen, who’s now working on Lilly’s HDL drug.

To contact the reporter on this story: Naomi Kresge in Berlin at [e-mail]

To contact the editor responsible for this story: Phil Serafino at [e-mail]