Goed nieuws voor Galapagos! Betreffende report op inhoudelijk draadje gezet.
Leerink Partners 26/10/'16
VERTEX PHARMACEUTICALS INCORPORATED Hedging Triple Combo Bets w/ Many Shots on Goal, Uncertain Safety Limits Upside
• Next Generation Corrector Safety Concerns Overhangs Phase II Triple Trials. The company’s triple development plans initially seemed straightforward and encouraging but became increasing more complicated during the conference call. Management announced that both drugs in phase Ia would advance to phase II, in both het-mins and homozygous delF508’s, in similar two-part triple combination trials. In explaining why they had chosen a multi-part format for each triple drug program, management disclosed that one of the two drugs had been associated with significant GI adverse events (Vx152) at the higher doses tested in phase Ia, while the other drug was associated with significant teratogenicity risks from pre-clinical studies (Vx440), thus restricting its use in women to those on “pre-specified, non-hormonal” contraception. This compound appears to be complicated by the occurrence of liver enzyme induction, which impairs the effectiveness of hormonal contraception, and presumably also has drug-drug interaction issues with other medicines also prescribed to CF patients. • Two Additional Next Generation Correctors Also Announced. Along with their announcement about the parallel phase II trials in both hetmin and delF508 homozygous CF patients, management also disclosed the development of a 3 rd “next gen” CF corrector (Vx659) that is being studied in a combined phase Ia/Ib trial (in a triple combination) in both healthy subjects and delF508/minimum function patients. The company described this next generation corrector as having greater in-vitro potency than either Vx440 or Vx152 and as being “only six months behind.”
• This is hard to understand given the one-year timeline required for the completion of the phase Ia trials for Vx440 and Vx152, and suggests that Vx659 might be on the “fast track” designed to catch up with Vx440 and Vx152 – presuming it has a more favorable pre-clinical profile than its predecessors. The company also announced a fourth next-generation corrector it plans to advance into clinical development in 2017.