Three of Europe's biggest drugmakers - AstraZeneca, Novartis and Sanofi - reported product setbacks, underlining the difficulties of developing new medicines to make up for those going off patent.

With the weakest pipeline of its European peers, AstraZeneca was hit hardest by a double blow to treatments for cancer and depression, which triggered $381.5 million in charges and will push 2011 profits to the lower end of its forecast range.

Novartis, meanwhile, faces plunging sales of blood pressure pill Rasilez after patients taking it actually did worse in a clinical trial, and Sanofi's hopes of competing in the new market for oral multiple sclerosis (MS) drugs were dented by failure in a head-to-head study.

While AstraZeneca's and Sanofi's experimental medicines were known to be risky projects, the setback for Rasilez - an established treatment - caught analysts by surprise.

Kepler's Martin Voegtli said the fact there were more adverse events when the Novartis drug was added to standard blood pressure pills was a "major setback" and was likely to lead to the drug being pulled from the market, wiping out an estimated $1.7 billion in peak annual sales.

AstraZeneca Vulnerable

Anglo-Swedish AstraZeneca is more vulnerable, given its limited pipeline of new drugs to offset looming patent losses on blockbusters like Seroquel for schizophrenia and Nexium for heartburn and ulcers.

Its shares, which already trade at a discount to the European sector, fell 2.3% on what Merchant Securities analyst Navid Malik described as further evidence of "pipeline capitulation."

AstraZeneca's olaparib will not progress into final Phase III testing for ovarian cancer, due to disappointing results in a mid-stage clinical trial, while experimental antidepressant TC-5214 failed to meet its goal in a second Phase III study.

AstraZeneca is developing TC-5214 with U.S. biotech partner Targacept.

Despite research and development impairment charges of $285 million for olaparib and $96.5 million for TC-5214, AstraZeneca still expects to hit its broad target for 2011 earnings - but it warned that core earnings per share, which exclude certain items, would now be in the lower half of the previously indicated range of $7.20 to $7.40.

Sanofi Lags In MS Race

French drugmaker Sanofi is looking in a weaker position in the competitive MS drug market after its experimental Aubagio pill failed to show it was better than Rebif, a commonly used injectable treatment from Germany's Merck KGaA.

But Aubagio, known chemically as teriflunomide, was well tolerated compared with Rebif, which caused more flu-like symptoms.

The trial was the second completed study of five efficacy studies of Aubagio, which Sanofi plans to use for its marketing application in Europe. Sanofi filed for U.S. approval in October and expects to file in Europe in the first quarter of 2012.

Berenberg analyst Alistair Campbell called the data disappointing, but said they did not change his low expectations for Aubagio, for which he forecasts peak sales of €200 million ($260 million).

Aubagio is one of the two MS drugs Sanofi has in late-stage development. The other is Lemtrada, which has shown it can significantly reduce both relapses and worsening of disability, although side effects remain an issue for the novel injectable treatment.