Filgotinib in psoriatic arthritis

Filgotinib in inflammation

PsA is an inflammatory form of arthritis, affecting up to 30% of psoriasis patients. In 2018, 3.5 million patients suffered from PsA in the U.S., EU5 and Japan and the market for PsA treatments was worth nearly $7 billion in 2018 in these seven major markets.1Sources: Decision Resources Group, Global Data, Galapagos Custom Research

PsA can cause swelling, stiffness and pain in and around the joints and cause nail changes and overall fatigue. Studies show that delaying treatment for PsA as little as six months can result in permanent joint damage. Early recognition, diagnosis and treatment of PsA are critical to relieve pain and inflammation and help prevent joint damage. Despite the availability of a number of treatment options, few current treatments effectively relieve the enthesitis (inflammation of the tendons or ligaments) and symptoms in the joints and the skin.

EQUATOR Phase 2 program with filgotinib in PsA

The EQUATOR Phase 2 trial was a multi-center, randomized, double-blind, placebo-controlled trial to assess the safety and efficacy of filgotinib in adult patients with moderate to severe active PsA. 131 patients were randomized in the trial in a 1:1 ratio to receive 200 mg filgotinib or placebo once-daily administered for 16 weeks. EQUATOR was recruited in eight European countries.

In May 2018, Gilead and we announced that the EQUATOR trial achieved its primary endpoint of improvement in the signs and symptoms of PsA at Week 16, as assessed by ACR20 score. There was an ACR20 response of 80% for filgotinib versus 33% for placebo (p<0.001). The ACR50 and ACR70 responses at week 16 were also significantly higher for filgotinib versus placebo (ACR50: 48% for filgotinib versus 15%, p<0.001; ACR70: 23% versus 6%, p<0.01).

Durable response in EQUATOR PsA Ph2

Durable response in EQUATOR PsA Ph2 – ACR20, ACR50, ACR70 (line chart)

Source: Coates et al. ACR 2019

This efficacy response was sustained in the open label extension of EQUATOR, up to 52 weeks:

Durable response in EQUATOR PsA Ph2

Durable response in EQUATOR PsA Ph2 – Equator open label extension (line chart)

Source: Coates et al. ACR 2019

Filgotinib was generally well-tolerated in the EQUATOR trial, with no new safety signals observed and similar laboratory changes compared to those reported in previous trials with filgotinib in RA patients. The adverse event rate was similar in both groups with mostly mild or moderate events reported. There was one serious infection in the filgotinib group, a patient who experienced pneumonia with a fatal outcome. One other patient receiving filgotinib developed herpes zoster. There were no cases of opportunistic infection, tuberculosis, thromboembolism, or malignancy. The full results of EQUATOR were published in The Lancet and presented in a plenary session at ACR 2018 (Mease et al. 2018), and a safety update through 52 weeks was presented at ACR2019 (Coates et al. 2019).

TEAEs of special interest

incidence
# of pts (%)
FIL 200 mg, n=65
wk 0-16

incidence
# of pts (%)
placebo, n=66
wk 0-16

rate/100 PYE
# of events
FIL 200 mg, PYE=160
wk 0-52

all serious infections

1 (1.5)

1.9 (3)

opportunistic infections

herpes zoster

1 (1.5)

0.6 (1)

malignancies

0.6 (1)

deep vein thrombosis

pulmonary embolism

major cardiac events (adjudicated)

0.6 (1)

deaths

1 (1.5)

0.6 (1)

Global PENGUIN Phase 3 program with filgotinib in PsA

In December 2019, Gilead dosed the first patient in the PENGUIN Phase 3 program in PsA. The PENGUIN program investigates the efficacy and safety of 100 mg and 200 mg filgotinib once-daily compared to placebo. PENGUIN 1 will compare the efficacy and safety of filgotinib, adalimumab, and placebo in approximately 1000 patients with active PsA who are naive to bDMARD therapy. PENGUIN 2 will measure efficacy and safety of filgotinib vs placebo in 390 patients with active PsA who have an inadequate response or are intolerant to bDMARD therapy. The primary endpoint of each trial is ACR20 response at Week 12, with multiple secondary endpoints on signs and symptoms of PsA up to week 24 in PENGUIN 1, and week 16 in PENGUIN 2.

1 Source: Decision Resources Group, Global Data, Galapagos Custom Research