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Quick Note: Galapagos NV (GLPG US, Buy) - Positive Top-line CF Results from ALBATROSS
November 20, 2017
Americas Biotechnology
Stock Rating: Buy
Target Price: USD 124.00
GLPG.OQ (USD 90.83)
Sunday night, GLPG reported positive top-line results from ALBATROSS, a Ph2 study of its CF corrector GLPG2222. ALBATROSS was conducted in patients with heterozygous gating mutation (F508del), a mutation that was shown to be amenable to GLPG2222 correction in cellular assays. Thirty seven patients received GLPG2222 orally administered at either 150mg, or 300mg QD, on top of a Kalydeco regimen. The trial recruited in just five months. Three triple combo trials are set to begin with first data expected 2H18.
Sweat Chloride Decreases Stat Sig, FEV1 Increased Dose Dependent. The randomized, double-blinded, placebo controlled Ph2 study’s primary objectives were to evaluate safety and tolerability as well as drug pharmacokinetics. Two doses, 150mg and 300mg PO, were tested—no serious AEs or discontinuations due to AEs were reported. Two measures of efficacy, sweat chloride concentration and percent predicted FEV1, were also measured for each of the three cohorts. Sweat chloride decreased in a dose-dependent manner, and ppFEV1 improved modestly (in a dose-dependent manner). Dose-dependent changes strengthen evidence for activity due to the drug’s MOA.
Concordant Dose Dependent Changes Are Promising and Bode Well For Triple Combo. Efficacy was dose-dependent and statistically significant; the decrease in sweat chloride concentration was 6 mmol/L in the highest dosing cohort. Change in ppFEV1 vs. baseline was +2.2%. By comparison, Kalydeco resulted in a nearly 50 mmol/L decrease in sweat chloride and a nearly 11 percentage point difference in ppFEV1. However, Orkambi (lumacaftor in combo with Kalydeco) is an FDA approved formulation that only had an FEV1 benefit over placebo of approx. 3%.
Results Similar to Tezacaftor-Ivacaftor in Similar Population. Earlier this month, it was reported that tezacaftor and Kalydeco produced a 4% absolute change in ppFEV1, and ~10 mmol/L decrease in chloride in a Ph3 study in patients with F508del mutations.
Moving to the Triple Combo: Three triple combo trials will test C1 corrector ‘2222 with either potentiator ‘2451 or ‘3067 and C2 ‘2737 or ‘3221. First up is triple of ‘2451+’2222+ ’2737, with data possibly in early 2H18. New 3067 potentiator addresses long half-life concerns of ‘2451, and patient studies could begin in 4Q17 for a dual combo, 1Q18 for a triple.