- Evaluation of C1 corrector GLPG2222 on top of ivacaftor (Kalydeco®[1]) in heterozygous Class III/F508del CFTR patients
- Patient study recruited within 5 months in Europe and Australia
- GLPG2222 was well tolerated dosed once daily for 28 days
- Dose dependent increase in FEV1
- Statistically significant dose dependent decreases in sweat chloride
- Further clinical validation of in vitro predictive platform
MECHELEN, Belgium I November 19, 2017 I Galapagos NV (Euronext & NASDAQ: GLPG) reports positive topline results from its ALBATROSS Phase 2 study in cystic fibrosis patients with C1 corrector GLPG2222.
The ALBATROSS study included 37 cystic fibrosis patients with a gating (Class III) mutation on one allele and F508del (Class II) mutation on the other allele. All patients were on long-term stable Kalydeco treatment (150mg twice daily) at screening and continued their Kalydeco treatment throughout the study. The ALBATROSS study was fully recruited within five months.
Primary objectives of this randomized, double-blinded, placebo controlled study were to evaluate the safety and tolerability and pharmacokinetics of novel C1 corrector GLPG2222 in this CF patient population. Once daily doses of 150mg GLPG2222, 300mg GLPG2222 or placebo were administered.
Overall, GLPG2222 was well tolerated, with observed treatment emergent adverse events being predominantly mild or moderate, and typical for a CF patient population. There were no serious adverse events reported and no discontinuations due to adverse events.
The targeted exposures of GLPG2222 were achieved in this patient study, further strengthening dosing modelling for the first investigational triple combination. Exposures achieved in patients were in line with those observed in healthy volunteers.
The additional activity observed with treatment with GLPG2222 on top of Kalydeco was in line with what was observed with tezacaftor combined with Kalydeco in a Phase 2 study in this population. A statistically significant dose dependent decrease in sweat chloride concentration was observed amounting to a decrease of 6 mmol/L in the 300mg cohort. Mean percent predicted FEV1 (ppFEV1) levels overall were 70% at screening (prior to treatment with GLPG2222). At the end of treatment with 300mg GLPG2222, ppFEV1 levels increased by 2.2%.
| Placebo (n=7) | 150mg (n=15) | 300mg (n=14) | |
| Sweat chloride, mean change D29 vs baseline, in mmol/L |
+5.6 (3.75^) |
-3.8 (2.55)* |
-6.0 (2.66)* |
| ppFEV1, mean change D29 vs baseline, % |
-0.8% (1.79)
|
-0.6% (1.23) |
+2.2% (1.28) |
* = p<0.05
^= LS-means (SE) from an ANCOVA model with treatment as factor and baseline as covariate
“The results of this trial are encouraging as they show that the addition of the novel CFTR corrector molecule GLPG2222 on top of highly efficacious CFTR modulator treatment already given for years in patients with gating mutations was well tolerated and may bring additional benefit to patients. Also, this clearly demonstrates the interest and willingness from the CF community to continue develop novel treatments for patients.” commented Prof. Scott Bell from the Prince Charles Hospital in Brisbane, Australia and principal investigator for ALBATROSS.
“The ALBATROSS results are the first results demonstrating that GLPG2222 is well tolerated in CF patients. In addition, the exposures achieved, coupled with the activity observed, support our dose selection plans for the investigational triple combination therapy,” said Dr. Piet Wigerinck, CSO of Galapagos. “We are impressed with the magnitude of the effects we saw on sweat chloride and FEV1 in patients whose treatment with ivacaftor has been optimized following years of therapy.”
GLPG2222 is an investigational therapy; its safety and efficacy have not been established.
About Galapagos
Galapagos (Euronext & NASDAQ: GLPG) is a clinical-stage biotechnology company specialized in the discovery and development of small molecule medicines with novel modes of action. Galapagos’ pipeline comprises Phase 3 through to discovery programs in cystic fibrosis, inflammation, fibrosis, osteoarthritis and other indications. Our target discovery platform has delivered three novel mechanisms showing promising patient results in, respectively, inflammatory diseases, idiopathic fibrosis and atopic dermatitis. Galapagos is focused on the development and commercialization of novel medicines that will improve people’s lives. The Galapagos group, including fee-for-service subsidiary Fidelta, has approximately 578 employees, operating from its Mechelen, Belgium headquarters and facilities in the Netherlands, France, and Croatia. More information at www.glpg.com.
SOURCE: Galapagos
