Galapagos NV recently released the positive top line results of a phase 1b study of tyrosine kinase 2 (Tyk2) inhibitor glpg3667 in the treatment of psoriasis. Glpg3667 was discovered by Galapagos company and is a special selective Tyk2 compound. In a randomized, placebo-controlled, double-blind phase 1b study, 31 patients with moderate to severe plaque psoriasis were treated. In the study, patients were randomly assigned to oral glpg3667 (low or high dose) or placebo in a ratio of 1:1:1 for 4 weeks. The main purpose of this study was to evaluate the safety, tolerance and clinical activity of glpg3667 at week 4.
The results showed that glpg3667 was well tolerated in phase 1b trial. One patient in the low-dose group was interrupted for one day due to deterioration of psoriasis. Most of the treatment-related adverse events (AE) were mild and transient. There were no deaths or serious adverse events in the four week study.
At week 4, 4 of 10 patients in the glpg3667 high-dose group achieved pasi50 response (psoriasis area and severity index [PASI] improved by at least 50% from baseline), and 1 of 10 patients in the placebo group achieved pasi50 response. However, there was no pasi50 response in glpg3667 low-dose group. The PASI scores of four responding patients in the glpg3667 high-dose group were improved by 52%, 65%, 74% and 81% respectively compared with the baseline, while one responding patient in the placebo group was improved by 52% compared with the baseline. At week 4, compared with placebo, high-dose glpg3667 also observed positive response signals for other endpoints (including affected body surface area, overall evaluation by doctors and patients).
Dr Walid ABI Saab, chief medical officer of Galapagos, said: “we are satisfied with the efficacy and safety of glpg3667 in patients with psoriasis after 4 weeks of treatment. Based on these results, we plan to launch the psoriasis global phase 2B project next year as part of our project to develop our selective oral Tyk2 inhibitor glpg3667, which aims to assess gplg3667 for a wide range of inflammatory indications. “
Dr Diamant Thaci, Professor of medicine at the comprehensive inflammatory medicine center of Lubeck University in Germany, said: “the pasi50 response score and other efficacy data after 4 weeks of treatment, combined with the observed safety, are very helpful to promote the compound to a larger scale psoriasis trial. The psoriasis population still needs more treatment options, especially oral therapy. “
Jyseleca filgotinib chemical formula (photo source: Wikipedia)
Galapagos is committed to the discovery and development of small molecule drugs with new mechanisms of action, some of which have shown good efficacy. Currently, the company is working with Gilead sciences to develop an oral anti-inflammatory drug, jyseleca (filgotinib).
Filgotinib is a highly selective Jak1 inhibitor, which was discovered and developed by Galapagos. Gilead and Galapagos reached an agreement with a total amount of US $2 billion at the end of December 2015 to jointly develop and commercialize filgotinib around the world. Due to the major setback in US regulation, the two sides revised the commercial and development agreement of filgotinib in December 2020. Galapagos will be responsible for the commercialization of filgotinib in Europe (the transition period is expected to be completed by the end of 2021), while Gilead will continue to be responsible for the distribution of filgotinib outside Europe, including Japan (where Gilead co sells filgotinib with Sinoma).
Filgotinib is being developed to treat a variety of inflammatory diseases, including rheumatoid arthritis, Crohn’s disease and ulcerative colitis.
Jyseleca has been approved for marketing in the European Union, the United Kingdom and Japan for the treatment of adult patients with moderate to severe rheumatoid arthritis (RA) who do not respond to or tolerate one or more disease modifying antirheumatic drugs (DMARD). In terms of medication, jyseleca can be used as monotherapy or in combination with methotrexate (MTX).
At present, jyseleca’s application for new indications for the treatment of ulcerative colitis (UC) is also under the regulatory review of the European Union, the United Kingdom and Japan. The specific application is for the treatment of adult patients with moderate to severe active ulcerative colitis (UC) who lack response to conventional therapy or biological agents, lose response, or intolerance. It is worth noting that due to safety considerations, the US FDA has not approved any indications for jyseleca.