Sales of monoclonal antibodies will almost double by 2013 to $49 billion as the ‘big five’ - Avastin, Herceptin, Rituxan, Humira and Remicade – are joined by the “emerging eight”, notes a new study.

The analysis by Datamonitor notes that the small molecule segment will continue to account for the majority of total pharmaceutical sales, but it is growing at a slower rate. In contrast, mAbs will still account for a modest share of total market sales in 2013, but will grow at an impressive rate of 10.9% from 2007–13.

The primary reason for the difference between small molecule and monoclonal antibody growth outlooks is the degree of exposure to generic competition, the report says, but it is not the only factor, says Datamonitor analyst John Bird. “mAbs currently – and will continue to do so in 2013 – command a three-fold average revenue per product premium over small molecules,” he says, because they address areas of “high unmet need and lower competitive intensity due to accessing a novel target space”.

The study says that “remarkably”, the three cancer mAbs – Avastin (bevacizumab), Herceptin (trastuzumab) and Rituxan (rituximab) – plus the two anti-inflammatories Humira (adalimumab) and Remicade (infliximab) – each have or are forecast to have annual sales greater than $3 billion from 2007-2013. Indeed, the big five are expected to retain their market leadership with a combined 60% market share by then.

However, Datamonitor has identified eight emerging therapies that are each forecast to demonstrate significant increases in annual sales – to greater than $500m – between 2007 and 2013. There are Elan/Wyeth’s bapineuzumab, Amgen/Eisai’s denosumab, AstraZeneca/Abbott’s Numax (motavizumab), Johnson & Johnson/Schering Plough’s golimumab, plus four already-approved drugs – Genentech/Novartis’s Lucentis (ranibizumab), Roche’s Actemra (tocilizumab), Biogen Idec/Elan’s Tysabri (natalizumab) and UCB’s Cimzia (certolizumab pegol).

Together, the ‘emerging eight’ will generate a combined increase in annual sales of approximately $11 billion between 2007 and 2013, Datamonitor says, noting that bapineuzumab and denosumab are “both commercially reminiscent of the ‘big five’ members in their embryonic launch phase. Each hold the promise of the ‘land grab’ of a novel target (amyloid beta and RANKL, respectively) and also address disease areas with high unmet need”.

However, the study warns that the “sheer novelty and unprecedented nature of their targets carries a significant risk of development failure”. Still, they could also lead therapeutic diversification of the mAb segment away from its historical core focus on oncology, immunology and inflammation and into new areas such as Alzheimer’s disease (bapineuzumab) and osteoporosis (denosumab).

Datamonitor adds on a technical note that one of the key competitive advantages of mAbs to date “has been their ability to modulate protein targets that no other molecule type can reach, most notably small molecules”. However, those mAbs that bind target proteins that possess a cytoplasmic tyrosine kinase domain “will face a potential threat from small molecule agents targeting this domain”.

Mr Bird says that for mAbs targeting receptor/ligand pairings which contain members of the receptor tyrosine kinase superfamily (such as Avastin and Herceptin), “tyrosine kinase domains present a weak point, or a ‘way in’ for direct small molecule competitors”. In contrast, those mAbs that bind target receptor/ligand pairings devoid of small molecule-suited hydrophobic pockets (Rituxan/CD20, denosumab/RANKL and bapineuzumab/amyloid beta) “look set to remain insulated from any direct small molecule competitive threat”.