Rheumatoid Arthritis Drugs in the Pipeline

What Does the Future Hold for RA Treatment?

In This Article

The drug pipeline for rheumatoid arthritis (RA)—what's currently in development by manufacturers—contains some promising new drugs that could help improve the outlook and quality of life for people with this debilitating disease. These include filgotinib, plivensia, and others you may or may not have yet heard of.

The introduction of biologics in the late 1990s revolutionized the treatment of RA, and, since then, researchers have uncovered a wealth of information about disease progression, symptom improvement, and how innovative future therapies could further improve life for people with RA. This knowledge is propelling research to improve the lives of patients.

RA treatments have traditionally focused on targeting inflammation pathways and responses, but now some researchers have shifted their focus to other elements that influence immune system malfunction and the progression of rheumatoid arthritis.

When a drug is in development, it means that the manufacturer is testing it to see if it has the desired effect and what side effects it may cause. This long and arduous process includes laboratory studies on microorganisms and animals, human trials, and the approval process of the U.S. Food and Drug Administration (FDA).

Filgotinib

In late 2019, Gilead Sciences, Inc., submitted a new drug application to the FDA for the selective Janus Kinase 1 (JAK-1) inhibitor filgotinib (GLPG0634). The application seeks approval for the oral medication as a treatment for adults "who are living with moderate-to-severe" RA.

JAK inhibitors work by hindering the activity of one or more of the Janus kinase enzymes, which are responsible for cell signaling that causes the inflammation and immune responses seen in RA.

A highly selective JAK-1 inhibitor targets a specific enzyme rather than a whole group. Researchers hypothesize that this narrower target could mean fewer side effects and higher potential doses.

Filgotinib has completed phase 3 clinical trials. In addition to the application submitted to the FDA, Gilead has also submitted a priority review application, which may speed up the approval process.

Peficitinib

Peficitinib is an oral JAK-1 and JAK-3 inhibitor under investigation for RA. Thus far, it's only approved for use as an RA drug in Japan, where it's marketed under the name Smyraf.

As a JAK-1 and JAK-3 inhibitor, peficitinib targets two specific Janus kinase enzymes. Two phase 3 trials have suggested that this drug can improve outcomes in people with moderate-to-severe RA who don't respond well to the drug methotrexate and other therapies.

Studies suggest that the drug improves symptoms and suppresses joint destruction.

Peficitinib is going through the FDA approval process for adults with moderate to severe RA who can't tolerate or have an inadequate response to methotrexate.

Its suggested use is as either a monotherapy (taken alone) or in combination with disease-modifying anti-rheumatic drugs (DMARDs).

Plivensia

Plivensia (sirukumab) is an injected interleukin-6 (IL-6) inhibitor. Interleukin-6 is a substance produced by your immune system that is involved in inflammation. Drugs that inhibit it are believed to help reduce inflammation.

In 2017, the FDA rejected the new drug application for Plivensia, citing an imbalance in the number of deaths in people taking the drugs versus the control group.  However, a 2018 RMD Open report says sirukumab's safety profile is much like that of any anti-IL agent. The FDA has yet to review this evidence.

Research indicates that Plivensia can reduce clinical signs and symptoms of RA and reduce damage over two years in comparison to DMARDs. Phase 3 trials suggest that it can significantly reduce RA symptoms and inhibit the progression of structural damage, and that it does so in people who don't have success with DMARDs.

If eventually approved, Plivensia would compete with two other IL-6 inhibitors currently on the market, Actemera (tocilizumab) and Kevzara (sarilumab). 

ART-I02

ART-I02 is being investigated by the biopharmaceutical company Athrogen. It's a gene therapy medication that may reduce interferon-beta (IFN-β), which produces proteins that promote the development of RA. 

Pre-clinical studies have found that one single injection of ART-I02 in animals is beneficial to managing the symptoms of RA and other types of arthritis, including osteoarthritis.

Researchers are now looking at the effect ART-102 has on humans.

ATI-450/CDD-450

This drug used to be designated CDD-450, but when Aclaris Therapeutics, Inc., acquired the company that was developing it, the designation changed to ATI-450. (Alpha-numeric designations are assigned before generic drug names.)

It's classified as a selective p38-alpha MAPK inhibitor, which means that it blocks cellular communication that can lead to inflammation.

A 2018 study reported in the Journal of Experimental Medicine finds ATI-450 can reduce the damage associated with RA. ATI-450 is designed to halt inflammation and may be able to reduce the damage associated with inflammatory autoimmune diseases, including RA.

In early 2020, Aclaris announced positive results from its first Phase I human trial and an intent to move on to Phase II studies.

This new drug is expected to have some advantages over biologics. Biologics need to be injected in the bloodstream, which makes them expensive and unpopular with patients. Additionally, your immune system may see biologic drugs as foreign invaders and reject them. ATI-450 would be available as a pill and isn't expected to have the same negative effect on the immune system.

Iberiotoxin

This unusual medication is based on scorpion venom. A 2018 study on rodents reported in the Journal of Pharmacology and Experimental Therapeutics demonstrated that components in scorpion venom may have the potential to reduce the severity of RA in animal models. In some cases, researchers say it even reversed joint damage.

Moreover, this study shows iberiotoxin may have fewer side effects than other types of RA medications.

The researchers suggest iberiotoxin could block the action of fibroblast-like synoviocytes (FLS), which they believe play a role in RA. They hypothesize that FLS may secrete damaging compounds into the joints that then attack immune cells, promoting joint inflammation and pain.

Research into iberiotoxin for RA is in the earliest stages, so little is known about its safety or effectiveness.

A Word From Verywell

The current research on RA drugs in the pipeline is ongoing, with scientists all over the globe exploring new ways to prevent and diagnose RA and to deliver treatments that are effective and less costly. The hope is to help people living with RA achieve high-quality and pain-free lives.

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