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Jyseleca in RA

RA is a chronic autoimmune disease that affects more than three million patients in the United States and Europe. RA is characterized by inflammation and degeneration of the joints. Patients suffer from pain, stiffness, and restricted mobility due to a persistent inflammation of multiple joints, ultimately resulting in irreversible damage of the joint cartilage and bone. The current market for RA treatments in the EU5 is approximately €3.3 billion, with 60% of patients treated with advanced therapies, including injectables, biological therapies and tsDMARDS.

Despite progress in the treatment of RA, there remains a considerable unmet need as sustained remission is rare.1

Oral therapies targeting the Janus kinase (JAK) signaling pathway are approved to treat inflammatory diseases. In 2003, we discovered JAK1 as a novel, differentiated target in an inflammation target discovery assay and subsequently developed filgotinib as a novel small molecule inhibitor with preferential selectivity for JAK1.

Within the commercial space of the RA market in the EU5, we observe an expanding market share for JAK inhibitors, compared to anti-TNF and other biologics. To date there are 4 JAK inhibitors approved for the treatment of RA in EU5, including Jyseleca as a JAK1 preferential inhibitor. The growth of the JAK class can be seen in both the total and dynamic (switchers and naïve patients) market share, as shown in the figure below.

Expanding JAKi market in EU5

JAKi RA market share (total) (bar chart)
Source: Therapy Watch, Q4 2021 (6-month average)

Regulatory approvals of Jyseleca in RA

In September 2020, Jyseleca (filgotinib 200mg and 100mg) obtained approval in European Union, Great-Britain, and Japan for the treatment of adult patients with moderate to severe active RA.

The European Summary of Product Characteristics for filgotinib, which includes contraindications and special warnings and precautions, is available at www.ema.europa.eu. The interview form from the Japanese Ministry of Health, Labour and Welfare is available at www.info.pmda.go.jp. The individual Great Britain and Northern Ireland Summary of Product Characteristics can be found at www.medicines.org.uk/emc and www.emcmedicines.com/en-GB/northernireland respectively.

In 2020, Gilead received a Complete Response Letter (CRL) from the U.S. FDA for the New Drug Application (NDA) for filgotinib. Consequently, Gilead decided not to advance with resubmission in the U.S. for approval of filgotinib as a treatment for RA.

Commercialization of Jyseleca in RA

In 2021, we took full ownership of the manufacturing and commercialization of Jyseleca in Europe and became MAH in 27 European countries, Iceland, Norway, and Liechtenstein. The medicine is now reimbursed in 14 countries, including the major markets of Germany, France, Spain, Italy, and Great Britain. In Central and Eastern Europe, Portugal, Greece and the Baltic countries, our partner Sobi is responsible for the distribution and commercialization. The graphic below represents the reimbursement progress throughout Europe since approval in September 2020. See details on the revised Gilead collaboration on filgotinib in the Notes to the consolidated financial statements.

Jyseleca reimbursement in RA

Jyseleca reimbursement in RA (graphic)

Following the amended agreement, Gilead remains responsible for Jyseleca outside of Europe, including in Japan where Jyseleca is approved in RA and is co-marketed with Eisai.

Safety and efficacy in the filgotinib RA development program

Filgotinib has shown favorable results in terms of onset of action, efficacy, safety, and tolerability from the FINCH Phase 3 and DARWIN Phase 2 clinical study programs.

As part of the filgotinib development program we initiated FINCH 4 in RA. The FINCH 4 study is a multi-center, open-label, long-term extension study to assess the safety and efficacy of filgotinib in patients with RA, enrolling subjects who completed either FINCH 1, FINCH 2, or FINCH 3 studies.

We and Gilead published integrated safety data from 7 RA studies in Annals of the Rheumatic Diseases (Winthrop et al 2021). Data were integrated from 3 Phase 3 studies (FINCH 1 – 3), 2 Phase 2 studies (DARWIN 1, 2), and 2 long-term extension studies (DARWIN 3, FINCH 4) including up to 5.6 years of filgotinib exposure, and over a median of 1.6 years. In this pooled analysis, filgotinib was well-tolerated, and no new safety concerns were identified. Adverse events of MACE and DVT/PE were rare and occurred in similar numbers among all treatment groups, and with similar incidence rate across dose groups. The data highlight the acceptable safety and tolerability profile of filgitinib as monotherapy and in conjunction with MTX/csDMARDs2 in RA.

In animal toxicology studies in the preclinical phase, filgotinib at an exposure dose above the approved dose in humans induced adverse effects on semen parameters. Consequently, Gilead and Galapagos committed to conducting dedicated male patient semen analysis studies in RA, AS, and PsA patients, called MANTA-RAy, and in UC and CD patients called MANTA, concurrent to all Phase 3 programs.

In March 2021, we were pleased to report on the primary endpoint with the MANTA and MANTA-RAy studies investigating the effect on semen parameters, indicating that 8.3% of patients on placebo and 6.7% of patients on 200mg filgotinib had a 50% or more decline in sperm concentration at week 13.

Phase 2 program for filgotinib in RA. DARWIN 1 explored three doses, in twice-daily and once-daily administration, for up to 24 weeks in RA patients with insufficient response to methotrexate (MTX) and who remained on their stable background treatment with MTX. DARWIN 2 explored three once-daily doses for up to 24 weeks in RA patients with insufficient response to methotrexate (MTX) and who washed out of their treatment with MTX. DARWIN 1 and 2 were double-blind, placebo-controlled trials which recruited approximately 900 patients globally and for which results were reported in 2015. DARWIN 3 is a long term extension trial in which all patients are on 200 mg filgotinib, except for U.S. males who are on 100 mg. The week 156 results from DARWIN 3 were reported in 2019
The U.S. Food and Drug Administration is an agency responsible for protecting and promoting public health and in charge of American market approval of new medications
Phase 3 program evaluating filgotinib in RA
Formerly known as GLPG0634, commercial name is Jyseleca. Small molecule preferential JAK1 inhibitor, approved in RA in European Union, Great Britain, and Japan, and in UC in European Union and Great Britain. Application for approval for ulcerative colitis was filed in Japan. Filgotinib is partnered with Gilead. Filgotinib currently is in Phase 3 trials in CD, and in a Phase 4 trial in RA
Major adverse cardiovascular events; a composite endpoint frequently used in cardiovascular research
A Phase 2 semen parameter trial with filgotinib in male patients with CD or UC
Methotrexate; a first-line therapy for inflammatory diseases
New Drug Application

1 1Chen Y, et al. Clin Rheumatol. 2019 Mar;38(3):727-738. doi: 10.1007/s10067-018-4340-7. Epub 2018 Oct 19.

2 2csDMARD, conventional synthetic disease-modifying antirheumatic drugs