Exelon

Drug Overview

Novartis first launched Exelon as a twice-daily oral formulation in Europe in 1998 and in the US in
2000 for the treatment of mild to moderate Alzheimer’s disease. This was followed by the launch of a
once-daily transdermal patch formulation of Exelon in the US and Europe in September 2007. In
Japan, the patch formulation was co-developed by Novartis’s Japanese partner Ono Pharmaceutical
under the brand name Rivastach and was launched in July 2011 (Ono Pharmaceutical, 2011a; Ono
Pharmaceutical 2011b). In 2013, the Exelon Patch 13.3mg was approved in the US and EU for the
treatment of severe Alzheimer’s disease, enabling Exelon to compete with Aricept for the on-label
treatment of all severities (PR Newswire, 2013; Medtrack, 2015).
In addition to inhibiting the activity of acetylcholinesterase (AChE), rivastigmine also inhibits
butyrylcholinesterase, another enzyme involved in the degradation of acetylcholine (ACh). It is also
the only cholinesterase inhibitor with a preferential selectivity for the G1 isoform of AChE. Unlike
other AChE isoforms, G1 expression levels are not decreased by Alzheimer’s disease and largely
predominate the brain. The dual cholinesterase inhibition and isoform specificity result in a
pronounced ACh effect, which underlies Exelon’s symptomatic relief. Furthermore, preferential
targeting of the G1 isoform limits the activation of peripheral associated side effects (FDA, 2015a;
Grossberg, 2003).

Analyst Outlook

Exelon (rivastigmine; Novartis/Ono Pharmaceutical) is a cholinesterase inhibitor, and its patch
formulation is unique in the Alzheimer’s disease market. The 2013 approval of the Exelon Patch’s
13.3mg dose allowed Novartis to target patients across the entire spectrum of disease severity,
competing fully with Aricept (donepezil; Eisai/Pfizer) and its generics. The success of the patch
formulation has enabled Novartis and Ono Pharmaceutical to maintain global sales of $1bn for
several years, despite the generic erosion of rivastigmine capsules. In September 2015, the first
generic equivalents of the Exelon Patch were launched in the US, jeopardizing the sales of Novartis’s
successful franchise. Furthermore, generic rivastigmine patches have been available in some countries
in the EU since 2013.