Sanofi-Aventis' Multaq Fails to Shine Following Mixed Data

December 24, 2008 Sanofi-Aventis' Multaq fails to shine following mixed data

Lisa Urquhart

Given that there are already small, but niggling, doubts about its chances of approval, what Sanofi-Aventis did not need was yesterday’s mixed results for Multaq, the arterial fibrillation drug, and the brightest hope in its R&D pipeline.

A study of 504 patients that compared Multaq with standard treatment showed that 36.5% of patients taking Multaq experienced atrial fibrillation after electrical cardioversion compared with 23.4% of those taking amiodarone. Electrical cardioversion is where an electrical current is used to reset the heart's rhythm back to its regular pattern, the success of the procedure tends to increase when anti-arrhythmic drugs are given beforehand.

Multaq, while less effective at stopping the recurrence of atrial fibrillation did, however, have a better safety profile than amiodarone and was better tolerated when gastro-intestinal events were excluded. Sanofi-Aventis will be releasing more data from the Dionysos trial next year, which it will be hoping will show more of a conclusive benefit over amiodarone.

Some analysts are now speculating that the mixed looking data from this trial means that its chances of gaining approval first time round are much slimmer, despite the fact that in previous trials it has shown itself to be highly efficacious and is currently only one of a handful of treatments in development for the disorder (see table below).

Anti-arrhythmic drugs in development

Annual WW Sales

($m)

Generic Phase Rank Product Company 2007 2014 Name (Current)

1 Multaq dronedarone Sanofi-Aventis Filed - 877

Astellas Pharma/Cardiome 2 Kynapid vernakalant Filed - 132 Pharma

- Propafenone SR propafenone Par Pharmaceutical Filed - -

- AZD1305 - AstraZeneca Phase II - -

Celivarone (SSR - celivarone Sanofi-Aventis Phase II - - 149744)

- ATI-2042 - ARYx Therapeutics Phase II - -

Total - 1,010

Multaq has already suffered a series of setbacks. In September 2006, it received an approvable letter after an earlier trial, Andromeda, which showed an increased risk of mortality with the drug in high risk patients. More recently, despite having fast track status that could have seen it approved by the end of this year, the FDA decided to hold an advisory committee in March, which could delay launch until mid 2009.

Much is riding on the success of Multaq. Some analysts are predicting that the drug has the potential to be a blockbuster, consensus sales forecasts from EvaluatePharma predict sales of $877m by 2014, well before its peak.

The drug is also Sanofi-Aventis’ most valuable pipeline product, worth $2.1bn to the company according to EvaluatePharma’s NPV Analyzer. It is also one of the group’s top 10 most valuable treatments. As such, it was not surprising that news of the data caused the shares to decline 5% to €44.15 over the last two days.

Poor approval track record

What any delay to approval will also do is further erode confidence in Sanofi-Aventis’ ability to get drugs into the market. The company, despite currently having 91 drugs in development, including 24 in phase III, last got a drug approved in the US in 2005, the worst track record in the industry (FDA bumps Sanofi-Aventis’s Multaq into slow lane, November 27, 2008).

Sanofi-Aventis, like other drug makers, needs new treatments to counter the effects of generic challenges to its marketed drugs. By 2012 seven of the French company’s drugs are set to lose patent protection including Plavix and Lovenox. All of these drugs are forecast to have combined sales of over $13bn this year (see table).

Sanofi Aventis drug patent expiries to 2012

Annual WW Sales ($m)

Generic Pharmacological Patent Rank Product 2007 2008 2009 2010 Name Class Expiry

Heparin, low Feb 1 Lovenox/Clexane enoxaparin 3,582 3,989 3,754 3,648 molecular weight 2012

Platelet ADP Nov 2 Plavix clopidogrel 3,324 3,761 3,298 3,204 antagonist 2011

May 3 Taxotere docetaxel Taxane 2,570 2,973 2,959 2,427 2010

Angiotensin II Sep 4 Avapro irbesartan 1,481 1,759 1,620 1,678 antagonist 2011

Mar 5 Ambien CR zolpidem Imidazopyridine 753 710 354 193 2009

leuprolide Jan 6 Eligard LHRH analogue 130 150 156 171 acetate 2011

Sep 7 Xyzal levocetirizine Anti-histamine 11 141 228 329 2012

Total 11,850 13,483 12,371 11,650

Things have not been helped by pipeline hiccups, including the withdrawal of weight-loss drug Acomplia from both the US and Europe following concerns of psychiatric side effects.

As such, with such a big patent hole to fill Sanofi-Aventis not only needs Multaq to get past the regulators on the first pass, but also speed up its drug development.