Shire plc / ViroPharma Incorporated

Hereditary Angioedema (HAE)

$327M Cinryze 2012 net sales (US)

Disease Overview

Hereditary Angioedema (HAE) is a rare autosomal dominant genetic disorder caused by deficient or dysfunctional C1 esterase inhibitor protein, leading to unpredictable, recurrent attacks of severe swelling in the skin, abdomen, and airway. Laryngeal attacks can be life-threatening. The disease is chronic, lifelong, and historically underdiagnosed.

Competitive Landscape

At deal close in 2013, the HAE market was small but premium-priced and rapidly expanding around prophylactic therapy. ViroPharma's Cinryze (plasma-derived C1-INH for routine prophylaxis) was the franchise crown jewel, generating $290M in US net sales over the first nine months of 2013, up 28% YoY (genengnews.com). Shire already commercialized Firazyr (icatibant), a bradykinin B2 receptor antagonist for acute attacks, plus had Kalbitor (ecallantide, plasma kallikrein inhibitor, marketed by Dyax) competing in the acute setting. CSL Behring's Berinert (acute) and Haegarda (later prophylaxis launch) were the main C1-INH competitors. The Shire/ViroPharma combination uniquely paired the leading prophylactic agent with the leading on-demand agent, giving Shire end-to-end HAE coverage and a dominant rare disease franchise expected to exceed $2B in combined revenues by 2014. Analysts called the 58x EBITDA price 'eye watering' but 'strategically very sound' (Panmure Gordon, per Nasdaq commentary). The deal cemented Shire's pivot toward rare disease and set up Cinryze sales to reach a projected $700M by 2018.