Rheumatoid Arthritis Drugs in the Pipeline

What Does the Future Hold for RA Treatment?

RA Drug Pipeline
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The drug pipeline for rheumatoid arthritis (RA) contains some promising new drugs that could help improve the outlook and quality of life for people with this debilitating disease. "Drug pipeline" is a phrase used to describe all the drugs that are currently in development by manufacturers.

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 future innovative therapies could further improve life for people with RA.

Current RA Treatments

So far, no one has discovered a cure for rheumatoid arthritis. Numerous drug options exist, but many of them are extremely expensive. In addition, most RA drugs are given by either infusion at a medical facility or self-injection. Researchers are currently working to create RA drugs that are less expensive and available in pill form.

With current treatments, goals include:

  • Reducing joint pain and inflammation
  • Increasing joint function
  • Preventing joint damage

Early and aggressive treatment is important for improving outcomes and preventing disability. Numerous successful therapies are available in a variety of forms. The most aggressive treatments include DMARDs, biologics and JAK inhibitors.

DMARDs

"DMARD" stands for disease-modifying anti-rheumatic drug. Common ones include:

These drugs block inflammation to preserve joints. Without them, the inflammation of RA would slowly destroy your joints, making them painful and, eventually, disfigured.

Biologics and Biosimilars

Also known as biologic response modifiers, biologics are designed to reduce or prevent the joint-damaging inflammation RA is known for.

Brand name biologics include:

Biologics target the molecules in the cells of your immune system and joints that are responsible for inflammation and joint damage. Several different types are available, each targeting a different molecule, including:

Some of these drugs must be given by self-injection while others require intravenous infusion in a doctor’s office or hospital setting. 

These medications are also very expensive and may not be covered by insurance. However, many less-expensive biosimilars are now on the market. In order to become approved by the U.S. Food and Drug Administration (FDA), biosimilars must be demonstrated to have no clinically meaningful differences from the original drug.

Some common biosimilars include:

  • Amjevita (adalimumab-atto, biosimilar to Humira)
  • Erelzi (etanercept-szzs, biosimilar to Enbrel)
  • Inflectra (infliximab-dyyb, biosimilar to Remicade)

JAK Inhibitors

Janus Kinase (JAK) inhibitors, such a Xeljanz (tofacitinib), Olumiant (baricitinib), and Rinvoq (upadacitinib) are the newest RA drugs. 

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

Rheumatoid Arthritis Drug Pipeline

RA treatments have traditionally focused on targeting inflammation pathways and responses. However, newer research is now focusing on the management of additional components that cause rheumatoid arthritis progression and immune system malfunction. 

Below are some of the up-and-coming drugs in the RA pipeline that may potentially reduce RA’s effects, and in some cases, even reverse the disease’s progression.

Filgotinib

Gilead Sciences, Inc. in late 2019 submitted a New Drug Application to the FDA for the selective JAK-1 inhibitor filgotinib (GLPG0634). The application seeks approval for the drug as a treatment for adults "who are living with moderate-to-severe" RA.

A selective JAK-1 inhibitor targets a specific enzyme rather than a whole group of them. Researchers hypothesize that this narrower target could mean fewer side effects and higher potential doses than with non-selective JAK inhibitors like the ones currently on the market.

Peficitinib

This drug is a 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.

Two phase-IIB studies have suggested that this drug can improve outcomes in rheumatoid arthritis.

Plivensia

Initially, the FDA rejected Johnson & Johnson’s Plivensia (sirukumab), 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.

More recent research indicates sirukumab can reduce clinical signs and symptoms of RA and reduce damage over two years in comparison to DMARDs. If eventually approved, sirukumab would compete with two other Il-6 inhibitors, Actemera (tocilizumab) and Kevzara (sarilumab). 

ART-I02

ART-I02 is currently 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.)

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.

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.

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

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 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 plays a role in RA. They hypothesize that it may secrete damaging compounds into the joints that then attack immune cells, which promotes joint inflammation and pain.

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, design clinical trials, measure treatment outcomes, and deliver treatments that are effective and less costly. The hope is to allow people living with RA high-quality and pain-free lives.

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