Regeneron, Sanofi drug slashes cholesterol in late-stage trial

Reuters

* Alirocumab cuts LDL-C by 47.2 pct vs 15.6 pct for Zetia

* Small clinical trial is just one of 12 to run until 2018

* Sanofi, Regeneron hope to seek drug approval by late 2015

By Ransdell Pierson and Natalie Huet

NEW YORK/PARIS, Oct 16 (Reuters) - A new type of cholesteroldrug from Regeneron Pharmaceuticals Inc and Sanofi SA, when used by itself, cut levels of "bad" LDLcholesterol almost in half in the first of a dozen late-stagetrials of the medicine.

The injectable drug, called alirocumab, is from a promisingnew class of medicines called PCSK9 inhibitors also beingdeveloped by Amgen Inc and other drugmakers. It hasbeen touted by industry analysts as a potential blockbuster thatcould bring annual sales of over $3 billion.

These man-made antibodies block a protein that prevents thebody from eliminating LDL cholesterol from the bloodstream andoffer a new way of fighting the build-up of artery-cloggingfatty deposits that put patients at risk of heart attacks.

They work differently from widely-used statins - pills thatinhibit the liver's production of LDL cholesterol in the firstplace, and to which some patients don't respond well.

In earlier mid-stage studies, when combined with statins,alirocumab and Amgen's own PCSK9 drug cut levels of LDLcholesterol by close to 70 percent, more than statins alone.

But the Phase III study unveiled on Wednesday involvedpatients who either took just alirocumab, or just Merck & CoInc's cholesterol drug Zetia (ezetimibe) - a pill oftenused by patients who cannot tolerate statins, whose side effectscan include muscle pain.

In this 103-patient study, alirocumab, which has to beself-injected every two weeks, reduced levels of LDL cholesterolby 47.2 percent after 24 weeks of treatment, compared to 15.6percent in those taking daily 10-milligram doses of ezetimibe.

"What we're seeing in the first Phase III trial of our drugis in line with what we saw in Phase II," George Yancopoulos,Regeneron's research chief, said in an interview.

"The good news here is there were no surprises, and that itsupports the good efficacy and safety profile we've seen todate."

Patients taking alirocumab started out with a low75-milligram dose every two weeks, but this was increased to 150milligrams at week 12 if their LDL levels at week eight wereabove 70. Most patients, however, remained on the low dosethroughout the study because they got their LDL levels belowthat threshold - an aggressive LDL target - by the eighth week.

"It shows that a low dose, when used as a monotherapy, canbe quite effective," Yancopoulos said, noting that no worrisomeside effects were seen in the study nor in earlier trials.

Shares in Sanofi, which rose 0.8 percent in early trade,were down 0.8 percent at 1150 GMT, roughly in line with theSTOXX Europe 600 Healthcare index.

Citi analyst Andrew Baum said the monotherapy data was"incrementally positive" but further trials on targeted patientgroups, such as patients with high cardiovascular risk, wereneeded to really assess the drug's utility.

Patients in the so-called Odyssey Mono trial had highcholesterol levels but were deemed to have only moderatecardiovascular risk due to the absence of many other riskfactors.

FIVE MORE YEARS OF TRIALS

The Odyssey Mono study is the first of 12 Phase III trialson some 23,000 patients and the drug's ultimate success willdepend on longer-term studies, some of which will only giveresults in around five years. But Sanofi and Regeneron arehoping positive trial data could be enough to get the drugapproved for some patients and on the market before then.

PCSK9 drugs are mainly aimed at the millions of people whoeither cannot tolerate statins such as Pfizer Inc's Lipitor or AstraZeneca Plc's Crestor or who cannot gettheir cholesterol levels under control with statins alone.

Yancopoulos said Regeneron and Sanofi hope to seekregulatory approvals by late 2015 for their drug, for use byitself and with statins.

Yancopoulos said Amgen's rival drug might reach market soonafter alirocumab, or even before. But he predicted neither drugwould have much of an advantage by getting approved first.

"But we're hoping to have bragging rights for the firstapproval," Yancopoulos said.

At an investor conference last month, Sanofi's CEO ChrisViehbacher said the drugmaker could look at nearly doubling itsstake in Regeneron, voicing confidence in the drug's success.Sanofi holds about 16 percent of Regeneron.

Deutsche Bank analysts said in a report last month that thenew drug could be priced at around $15 per day, comparable tothe cost of injectable diabetes drugs known as GLP-1s, such asNovo Nordisk's Victoza.

"Today's results should go some way to building confidencein Sanofi's improving pipeline capability and in our view formsthe first step to bridging credibility following recent poorfinancial results," Deutsche Bank wrote in a note on Wednesday.

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