OBJECTIVES: Drug development productivity has decreased over the past 10 years. The objectives are to a) better describe the reasons for discontinuations and b) help define the scale of the issue around discontinuing products and additional indications for reasons related to an anticipated lack of pricing and reimbursement flexibility. METHODS: A restricted and confidential survey to four pharmaceutical companies on their discontinued projects for lead and follow-on indications during the period 2005-2009. Reasons for discontinuation distinguished two major categories, ‘technical’ (including failure to meet safety or efficacy targets) and ‘commercial’ reasons. RESULTS: The four companies reported a total of 1,053 projects which had been active during the period 2005-2009. Of those, 51% were discontinued (n=541) by the end of 2009; 332 were lead indications and 209 were follow-on indications. About 72% of discontinuations for lead indications were for technical reasons. The pattern for follow-on indications is more complex. Technical reasons triggered a smaller proportion of discontinuations, presumably because many were addressed with the lead indication. However, a greater percentage of the discontinuations were after Phases II and III, implying higher costs to this point. Portfolio prioritisations and exiting the disease area accounted for 20% of discontinued projects. CONCLUSIONS: The results for lead indications reinforce previous results about the growing importance of non-technical i.e. commercial reasons as drivers for project discontinuations, around 20-25% in our sample. However, our results show for the first time an analysis for follow-on indications and where no comparison to previous literature is possible.