Rheumatoid Arthritis Drugs in the Pipeline

What Does the Future Hold for RA Treatment?

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The rheumatoid arthritis (RA) drug pipeline—what's currently in development by manufacturers—contains some promising new medications. They could help improve the outlook and quality of life for people with this debilitating disease.

Drugs that have been in development include:

  • Peficitinib
  • Plivensia
  • Iberiotoxin
  • Others too new to have names

This article tracks their progress through the testing and approval phase.

Research Scientist Looks into Microscope. He's Conducts Experiments in Modern Laboratory.
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When a drug is in development, it means that the manufacturer is testing its effectiveness and safety. This long, arduous process includes laboratory studies on microorganisms and animals, human trials, and, finally the Food and Drug Administration (FDA) approval process.

RA Drug Trends

The introduction of biologics in the late 1990s revolutionized the treatment of RA. Since then, researchers have uncovered a wealth of information about:

  • Disease progression
  • Symptom improvement
  • How innovative future therapies could further improve life for people with RA

This knowledge is propelling drug research forward. RA treatments have traditionally targeted inflammation pathways and responses.

But now some researchers have shifted their focus to other elements, including immune system malfunction and the progression of the disease.

Peficitinib

Peficitinib is an oral Janus kinase 1 (JAK-1) and JAK-3 inhibitor under investigation for rheumatoid arthritis.

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

Thus far, it's approved for use as an RA drug in Japan and Korea, where it's marketed under the name Smyraf.

Two phase 3 trials suggested this drug can improve outcomes in adults with moderate-to-severe RA who haven't respond well to the drug methotrexate and other therapies. Studies suggest peficitinib improves symptoms and suppresses joint destruction.

Peficitinib is going through the FDA approval process. Its suggested use is as either a monotherapy (taken alone) or in combination with other disease-modifying anti-rheumatic drugs (DMARDs).

Filgotinib

In late 2019, Gilead Sciences, Inc., submitted a new drug application to the FDA for the selective JAK-1 inhibitor filgotinib. The FDA in 2020 rejected the application due to concerns over testicular toxicity. Filgotinib is approved for RA in Europe and Japan under the brand name Jyseleca.

Plivensia

Plivensia (sirukumab) is an injected interleukin-6 (IL-6) inhibitor. Interleukin-6 is a substance made 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 excess 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.

Phase III trials suggest it can significantly reduce RA symptoms and inhibit the progression of structural damage, and that it does so in people who didn'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). 

Iberiotoxin

This unusual medication is based on scorpion venom. A 2018 study on rodents suggested components of 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.

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.

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 for 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. It's designed to halt inflammation in RA and other inflammatory autoimmune diseases.

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. Unlike biologics, it's available as a pill, so it doesn't need to be injected in the bloodstream. That makes it less expensive and easier to take. Also, the immune system sometimes rejects biologics. ATI-450 isn't expected to have the same negative effect on the immune system.

Summary

Drugs in the RA pipeline include JAK inhibitor peficitinib, interleukin-6 inhibitor Plivensia, scorpion venom-derivative iberiotoxin, interferon-beta drug ART-102, and selective p38-alpha MAPK inhibitor ATI-450.

The JAK inhibitor filgotinib was rejected by the FDA and is no longer in development in the U.S.

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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