On 6th May, 2009, Roche announced the approval of Avastin for the treatment of glioblastoma multiforme – the fifth approved indication for the angiogenesis inhibitor – after it had initially been launched in metastatic colorectal cancer in early 2004. After an early forecast from October 2004 predicted sales of $1.2 billion by 2012 (1), by 2005 Avastin had already surpassed this figure with sales of $1.4 billion (2). According to Roche, 2008 sales were $4.9 billion (3), and recent forecasts anticipate Avastin to become the industry’s biggest selling product by 2013, with sales of $8.1 billion in 2012 (4). Genentech’s own forecasts for the US range from $6.7 billion (probability adjusted) to $10.2 billion (unadjusted for probability) in 2015 (5). Whereas one might be tempted to explain this huge difference in forecasts for the same product over time with the inherent difficulties of predicting the future, there is another factor in play: a tremendously successful lifecycle management programme with multiple therapeutic expansions. Roche/Genentech’s anti-VEGF-R antibody exemplifies a common theme in oncology and other therapeutic areas. It is efficacious not only in the original indication, but has successfully been developed in several additional tumour indications, showing the expansion potential of the drug.
The example of Avastin illustrates how important strong lifecycle management, after obtaining the initial approval, has become in an industry that is wrestling with poor R&D productivity and more demanding payers and regulators. In addition, a more aggressive generics industry and the rapidly evolving field of biosimilars further increase the pressure on originators to realise as much value as possible during the precious years of market exclusivity.
DEFINITION OF LIFECYCLE MANAGEMENT
The term lifecycle management (LCM) means different things to different people – therefore, a clear definition is needed. As illustrated in Figure 1, LCM in the biopharmaceutical industry comprises a continuum of measures, ranging from relatively small modifications of the drug product with limited effort and risk, to demanding developments – in terms of time, costs and risk – of an existing drug in a new indication. Some people even include modified versions of existing molecules in LCM. However, here we will focus on what is arguably the biggest lever for value creation – therapeutic expansion, defined as the development of existing products for approval in new indications.
TRUE VALUE ADDED?
As one countermeasure against the ongoing R&D productivity crisis, many companies have put a strong emphasis on LCM activities, often establishing ‘lifecycle teams’ that replace the classical project development teams, once initial approval has been obtained. However, classical LCM measures, such as reformulations, new dosages or fixed-dose combinations, are increasingly viewed as attempts to secure their incomes at the expense of other stakeholders in the healthcare environment, such as payers or even patients. Hence, healthcare systems are reluctant to accept and to pay premium prices for such products, and the impact of such measures in prolonging lifecycles of drugs is questionable in a future where health technology assessment – by authorities such as NICE – will be increasingly adopted by payers across the globe.
Therefore, LCM measures have to prove their value to patients and the healthcare environment in a similar way to true new molecular entities (NMEs). It is crucial to developers – whether small biotechs or Big Pharma players – that they both maximise and fully exploit the potential of a drug early in its lifecycle. These two aspects can be combined in following a therapeutic expansion strategy, as shown in the example of Avastin.
A prerequisite for such a strategy is the therapeutic expansion potential of the drug based on the mechanism of action (MoA) and the targeted disease pathway. Drugs addressing a mono-causal genetic disease such as phenylketonuria (for example, Biomarin’s Kuvan, which reduces phenylalanine levels in these patients) are most likely to have only a very limited expansion potential into other indications, or none at all (although niche drugs can still become ‘nichebusters’ based on the unmet need, the therapeutic benefit and respective price, as Genzyme’s Cerezyme exemplifies).
