Development and Marketing of INCIVEK (Telaprevir; VX-950): A First-Generation HCV Protease Inhibitor, in Combination with PEGylated Interferon and Ribavirin

In the years before the development of direct-acting antiviral (DAA) drugs, patients were treated with a toxic combination of PEGylated interferon (P) and ribavirin (R) which was associated with a low success rate in patients with the most common genotype 1 hepatitis C virus (HCV) infection (40–50%), significant treatment-limiting side effects, and a long (48-week) duration of treatment. The HCV protease inhibitor telaprevir (VX-950) was discovered as part of a research collaboration between Vertex and Eli Lilly scientists. Clinical development of telaprevir in combination with PEGylated interferon alfa plus ribavirin (PR) was in collaboration with Tibotec (Janssen) and Mitsubishi Tanabe Pharma. INCIVEK (telaprevir) in combination with PR was approved in 2011, 10 days after the approval of Schering-Plough/Merck’s HCV protease inhibitor VICTRELIS (boceprevir), also in combination with PR. Both INCIVEK and VICTRELIS had similar safety and tolerability concerns, similar efficacy, three times daily dosing, and similarly complex treatment plans requiring significant attention by medical personnel. INCIVEK’s list price was higher than VICTRELIS, and INCIVEK was Vertex’s first launch, whereas Schering-Plough had been a HCV market leader with sales of Peg-INTRON/Rebetron. This chapter will briefly review the scientific challenges faced in the development of telaprevir and INCIVEK, as this story has been the subject of numerous review articles and book chapters. More emphasis will be given to the lesser-known story of how Vertex worked to prepare the HCV market, and we will unpack the variables contributing to the conundrum of why, despite being similar drugs, INCIVEK significantly outsold VICTRELIS.