Pipeline is fixed, says Novartis

Two years after reforming its R&D process Novartis said it has seen a 40 per cent increase in productivity, and declared the pharmaceuticals research strategy a success in delivering novel compounds to the clinic. This reflects the benefits of sustained investments in R&D, the Swiss company told an investor meeting this week (19 November).  

A total of 88 new entities are in the pipeline, a 40 percent increase since 2005. And productivity is up, with 80 percent of compounds that were successful in proof-of-concept clinical trials in 2006-2007, making it through to Phase II/III trials, a 60 percent improvement from trials during 2003-2005.

Novartis has put the priority on diseases where the greatest patient need is coupled with strong molecular understanding of the disease. It is selecting homogeneous clinical trial populations, either by testing for genes that are known to be causative or through biomarkers, and says this approach has improved the success rate from exploratory to confirmatory clinical development.

“Our strategy is working to deliver more effective medicines to patients rapidly,” said Mark Fishman, President of the Novartis Institutes for BioMedical Research. “In a relatively short time we have dramatically increased the size and power of our pipeline and believe many of these compounds have the potential to change the practice of medicine.”

Novartis has been building its position in biological therapeutics, especially monoclonal antibodies, and these now constitute 25 percent of the pre-clinical research portfolio. Clinical development has been expedited by a new Biologics Unit, dedicated specifically to protein therapeutics. A 2007 survey shows Novartis has 14 biological projects in clinical development, ranking among the top competitors in the pharmaceutical industry.

 Novartis says it has been consistently ranked as having one of the industry's strongest and most novel pipelines, with 139 projects in clinical development.

“We are working to transition pharmaceuticals development into highly integrated teams […] with biotech-like intensity, focus and flexibility,” said Trevor Mundel, Head of Global Development Functions.

Another important shift is a move to model-based drug development. The FDA has encouraged the industry to adopt quantitative evaluation from empirical analysis in early-stage research.

A drug-disease model translates quantifiable knowledge and beliefs about disease processes and drug action into predictions of measurable markers and responses of interest to drug development scientists, payers and regulators. It is useful in accelerating clinical trials, especially dose escalation. The Novartis Modeling & Simulation group has 50 researchers.

One example of this approach was the development of BAF312 that is planned to enter late-stage studies in 2009 for treating multiple sclerosis. Applying lessons from another compound, FTY720, which is now in Phase III trials for multiple sclerosis, the Modeling & Simulation team was able to accelerate the dose selection decision, provide a narrower range of doses for Phase III and reduce by over 50 percent the number of patients in the Phase II group.