FDA approves guselkumab for psoriatic arthritis

July 16, 2020

Guselkumab becomes the first IL-23 inhibitor approved for treatment of psoriatic arthritis by the U.S. Food and Drug Administration (FDA) following positive phase 3 results from two trials investigating the safety and efficacy of the drug.

Physicians now have another option to treat patients with psoriatic arthritis (PsA), with today’s approval of guselkumab (Tremfya, Janssen Pharmaceutical Companies of Johnson & Johnson) by the U.S. Food and Drug Administration (FDA). Guselkumab has been approved for treatment of active PsA in adult patients, making it the first selective interleukin-23 (IL-23) inhibitor approved for active PsA.

Guselkumab is a fully human monoclonal antibody and can be used as monotherapy or in combination with Disease Modifying Anti-Rheumatic Drugs (MARD) like methotrexate.

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"Tremfya is the first and only selective IL-23 inhibitor approved for both active psoriatic arthritis and moderate to severe plaque psoriasis, as well as the only biologic approved for the treatment of psoriatic arthritis to have improvement in fatigue as measured by FACIT-F included in the U.S. Prescribing Information. Today's approval marks an exciting milestone as we follow the science and search for solutions for patients with these complicated diseases," says David M. Lee, M.D., Ph.D., therapeutic area head of immunology at Janssen Research & Development.1

The approval is based on the results of two phase 3 randomized, placebo-controlled, double-blind trials (DISCOVER-1 and DISCOVER-2) that investigated the safety and efficacy of guselkumab versus placebo in 1,120 patients with active PsA who experienced an insufficient response to standard therapies.

Additionally, DISCOVER-1 had 31% of patients who had been treated with a maximum of two anti-tumor necrosis factor alpha (anti-TNFα) biologics. Meanwhile, all DISCOVER-2 patients were naïve to biologic therapy. Fifty-eight percent of subjects from both trials had previous concomitant methotrexate use.

Patients were randomized to either receive guselkumab 100 mg every four weeks (q4w) or every eight weeks (q8w) over the course of 52 weeks, or placebo with a switch to guselkumab q4w at week 24 for the remainder of the 52 weeks.

“The DISCOVER study program is the first time we’re seeing one-year phase 3 results evaluating an antibody with this mechanism of action (an antibody that selectively binds to the p19 subunit of IL-23 and inhibits its interaction with the IL-23 receptor) in active psoriatic arthritis,” says Alyssa Johnsen, M.D., Ph.D., vice president and rheumatology disease area leader at Janssen Research & Development. “We understand that targeting IL-23 can be effective and safe for the treatment of psoriasis, and now demonstrate that Tremfya is also effective in psoriatic arthritis. We’ll continue to advance research in IL-23 and psoriatic arthritis to gain greater understanding of the long-term benefits of treatment.”3

A release from the company states that the American College of Rheumatology (ACR) response rates included non-responder imputation (NRI) data in the results, which labels patients who withdrew from the studies after week 24 as non-responders.2

Results of the DISCOVER-1 study showed 73% of guselkumab q4w and 60% of guselkumab q8w achieved an ACR20 response compared to 22% of the placebo group (p<0.0001), while 54% of guselkumab q4w and 39% of guselkumab q8w achieved ACR50 at week 52 (NRI).

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In the DISCOVER-2 trial, 71% of guselkumab q4w and 75% of guselkumab q8w patients achieved ACR20 versus 33% of placebo (p<0.0001) at week 52, while 46% of guselkumab q4w and 48% of guselkumab q8w patients achieved ACR50 (NRI).

Guselkumab also relieved soft tissue pain and inflammation in the fingers and toes of patients in both trials, with 50% reporting resolved enthesitis in pooled analysis of both studies at week 24 versus 29% of placebo (p=0.0301). Dactylitis was also resolved in 59% of combined guselkumab patients compared to 42% placebo (p=0.0301) at week 24.1

Additionally, both studies demonstrated an improvement in psoriasis skin manifestations with 83% of guselkumab q4w, 69% of guselkumab q8w and 82% of placebo to guselkumab q4w patients in DISCOVER-1 and 84% of guselkumab q4w, 77% of guselkumab q8w and 84% of placebo to guselkumab q4w patients in DISCOVER-2 achieved a rating of clear (0) or almost clear (1) from baseline in skin improvement according to the Investigator’s Global Assessment (IGA) scale.2

Observed adverse events (AEs) of both DISCOVER trials were consistent with AEs of previous studies.

“Psoriatic arthritis is a complex disease and patients can suffer from a variety of symptoms, including inflammation of the joints and surrounding soft tissues, as well as the skin lesions associated with psoriasis,” says Dr. Johnsen. “These results demonstrate that inhibition of IL-23 is efficacious not just for psoriasis, but also for the musculoskeletal signs and symptoms and the impacts on physical function that define psoriatic arthritis.”

Currently, guselkumab is approved to treat adult active PsA in the U.S., Brazil and Japan, and moderate-to-severe plaque psoriasis in the U.S. Canada, Japan, European Union and other countries.

References:

1. TREMFYA (guselkumab) Approved by U.S. Food and Drug Administration as the First Selective Interleukin (IL)-23 Inhibitor for Active Psoriatic Arthritis. (2020, July 15). Retrieved July 15, 2020, from https://www.firstwordpharma.com/node/1740173?al=3a2380-a882871cf1564cc5f229595ac3bb61d7%5E%7C%5EMTEwOTg5Ng

2. New First-in-Class Phase 3 TREMFYA®▼ (guselkumab) Data Demonstrate Improvement in Psoriatic Arthritis Joint and Skin Symptoms at Week 52. (2020, June 03). Retrieved July 15, 2020, from https://www.businesswire.com/news/home/20200603005461/en/New-First-in-Class-Phase-3-TREMFYA%C2%AE%E2%96%BC-guselkumab-Data

3. Johnsen, A. (2020, June 25). DISCOVER-1 and DISCOVER-2 Guselkumab Results [E-mail interview].