Jazz Pharmaceuticals plc / Gentium S.p.A.

Severe Hepatic Veno-Occlusive Disease (VOD/SOS) post-HSCT

$60M Jazz expected $50-60M incremental annual revenue from Defitelio at deal time

Disease Overview

Hepatic veno-occlusive disease (also called sinusoidal obstruction syndrome, SOS) is a life-threatening complication of hematopoietic stem cell transplant conditioning, in which sinusoidal endothelial injury blocks small hepatic veins, causing painful hepatomegaly, ascites, jaundice, and multi-organ failure. Severe VOD with multi-organ dysfunction historically carried mortality above 80% with only supportive care.

Competitive Landscape

At the time of the December 2013 Jazz-Gentium deal, severe hepatic VOD post-HSCT had no approved therapy in the US and only supportive care globally. Gentium's Defitelio (defibrotide) became the first and only therapy approved by the European Commission (October 2013) for severe hepatic VOD in adults and children undergoing HSCT. Defibrotide had a complicated regulatory history — the FDA had refused to file a 2011 NDA, prompting Gentium to withdraw, while EMA later granted full approval. Off-label use of antithrombin III, tissue plasminogen activator (tPA), and N-acetylcysteine had been attempted historically but lacked controlled data. Jazz acquired Gentium for ~$1B at $57/share to add Defitelio to its hematology/oncology orphan portfolio alongside Erwinaze (asparaginase). Jazz subsequently obtained North/South American rights from Sigma-Tau in 2014 and ultimately won FDA approval for Defitelio in March 2016 — five years after the original FDA rebuff. Source: https://www.fiercebiotech.com/financials/jazz-pharma-trades-1b-for-gentium-and-a-well-traveled-orphan-drug