GLPG0634 at the EULAR 2014 in Paris

GLPG0634 is selective inhibitor of Janus kinase 1 (JAK-1) and I have been quite thrilled by this new drug since the ACR 2012 in Washington. The big news is, GLPG0634 has a name now: filgotinib.

F. Namour and colleagues presented [THU0123]: "DOSE SELECTION OF GLPG0634, A SELECTIVE JAK1 INHIBITOR, FOR RHEUMATOID ARTHRITIS PHASE 2B STUDIES: PK/PD AND EXPOSURE-DAS28 MODELING APPROACH". Conclusions: "Current modelling and simulation on the basis of early clinical data suggests that the pharmacokinetics of GLPG0634 is dose proportional at doses up to 200 mg QD, in agreement with observed data, and shows that both GLPG0634 and its main metabolite contribute to biomarker response. Simulations of the pSTAT1 and DAS28 dose-response relation suggest that the efficacy is favorable up to a daily dose of 200 mg GLPG0634, with clinical response in the range of that observed with registered compounds. A daily dose range from 50 to 200 mg is currently being tested in the DARWIN Phase 2B program."

C. Belleville-Da-Costa and colleagues presented [THU0138]: "GLPG0634M1, A MAJOR METABOLITE OF THE JAK1-SELECTIVE INHIBITOR GLPG0634, IS ALSO JAK1-SELECTIVE AND EFFICIENT IN THE RAT CIA MODEL". I skip this one.

F. Namour and colleagues presented [AB0460]: "GLPG0634, A SELECTIVE JAK1 INHIBITOR, CONFIRMS ITS LOW LIABILITY FOR DRUG-DRUG INTERACTIONS". Let's skip this one, too.

Darwin returned from his voyage with the beagle in 1836 and published his abstract "On the Origin of Species by Means of Natural Selection, or The Preservation of Favoured Races in the Struggle for Life" in 1859. Let's hope that the DARWIN study will publish results more quickly.

Links:

http://rheumatologe.blogspot.de/2013/06/glpg0634-at-eular-2013.html

http://rheumatologe.blogspot.de/2012/12/glpg0634-at-acr-2012-in-washington.html

GLPG0634 at the EULAR 2013

GLPG0634 is selective inhibitor of Janus kinase 1 (JAK-1). And I had been quite thrilled by this new drug at the ACR 2012 in Washington. Now, I was eager to see, what new developments would be presented at the EULAR 2013 in Madrid.

B. Vayssiere and colleagues presented a rodent study [THU0116]: “Biological effects of the jak1 selective inhibitor GLPG0634 on inflammation markers in arthritic mice”. Conclusions: “ … These data establish that selective JAK1 inhibition by GLPG0634 is sufficient to mediate strong efficacy in an established arthritis model …”. That wasn’t so thrilling.

F. P. Vanhoutte and colleagues presented [THU0229]: “Safety and efficacy of GLPG0634, a selective JAK1 inhibitor in patients with rheumatoid arthritis: results of a 4-week phase II a dose ranging, multi-center trial”. Conclusions: “These early clinical results demonstrate that selective inhibition of JAK1 by once-daily dosing of GLPG0634 from 75 mg to 300 mg is efficacious and generally well tolerated for 4-weeks treatment of RA, and confirm data from a previous study at a 200 mg daily dose. A dose of 30 mg QD was suboptimal for efficacy. Larger, longer term studies in RA are being initiated to evaluate optimal doses for efficacy and safety.” I looked into the results and agree with the authors’ conclusions.

F. Namour and colleagues presented a third study [THU0236]: “Once-daily dosing of GLPG0634, a selective JAK1 inhibitor, is supported by its active metabolite“. Conclusions: “The results of these studies indicate that an active metabolite supports the activity of GLPG0634. The long half-life of this metabolite provides a lasting effect, though at a lower level of JAK1 inhibition than GLPG0634. …”.

As EMEA seems to be reluctant to approve tofacitinib, maybe GLPG0634 has a better chance. With two PK inhibitors prices might come down to level, where it’s affordable for society. So I wish both drugs good luck!

Link:
http://rheumatologe.blogspot.de/2012/12/glpg0634-at-acr-2012-in-washington.html

GLPG0634 at the ACR 2012 in Washington

New data from the EULAR 29013 in Madrid: http://rheumatologe.blogspot.de/2013/06/glpg0634-at-eular-2013.html

GLPG0634 is selective inhibitor of Janus kinase 1 (JAK-1). If you look at the development of NSAIDs you see a similar phenomenon: non-selective NSAIDs that also block COX-1 have certain side effects, whereas COX-2 selective NSAIDs don’t have these side effects. With JAK-inhibitors it seems that JAK-2-driven side effects limit the use of non-selective JAK-inhibitors. GLPG0634 has a 30-fold selectivity for JAK-1 over JAK-2 in human whole blood.

F. Namour and colleagues presented: "Once Daily High Dose Regimens of GLPG0634 in Healthy Volunteers Are Safe and Provide Continuous Inhibition of JAK1 but Not JAK2." (Abstract No. 1331). Conclusion: “At high doses, exceeding those showing high level efficacy in a 4-week RA patient study, GLPG0634 was well tolerated and safe in healthy volunteers. No safety signals were found with GLPG0634; …”

F. Vanhoutte and colleagues presented: "Selective JAK1 Inhibition in the Treatment of Rheumatoid Arthritis: Proof of Concept with GLPG0634" (Abstract No. 2489). Results included: “GLPG0634 met the primary endpoint of significant improvement in ACR20 response rate.” Conclusions included: "These early clinical results are the first to demonstrate that selective inhibition of JAK1 is efficacious and safe for the treatment of RA. Consistent with the lack of inhibition of JAK2, no anemia was observed. ..."

Let´s see if this compound by Galapagos NC is going to make it. If it shows the same efficacy as tofacitinib and has less side effects because of JAK-1 selectivity, well then … but let’s not dream and wait for results of further studies. Of course, we wait eagerly! Good luck, Galapagos!