New gene therapy drug for rheumatoid arthritis undergoes phase 1 trial 

Arthrogen, a biopharmaceutical company specializing in gene therapy, is now recruiting individuals with rheumatoid arthritis to test the new drug ART-I02.

 
Khun Nantida does not wear clothes with buttons. Most of her pants have waistbands and do not require zipping. She uses only electric toothbrushes because she cannot brush her teeth as efficiently on her own. When Khun Nantida cooks for her children, she makes sure to fasten the lids  of the spice bottles loosely so that she can open them easily the next day. Khun Nantida, a forty-year-old mother of three, has rheumatoid arthritis.
 
Although the picture above is rhetorical, it is a common scenario for many individuals living with rheumatoid arthritis. Getting out of bed, showering, and getting dressed—all everyday routines—can become burdensome for those with rheumatoid arthritis. Rheumatoid arthritis affects over 600,000 Thais and also about 220,000 foreign expats living in Thailand. It affects more women than men. And researchers expect this number to increase steadily over time.
 
Rheumatoid arthritis is accompanied by symptoms of swollen, stiff, and painful joints. Individuals also experience joint warmth, redness, and deformity, as well as an overall decrease in mobility. While doctors are still unable to identify the exact cause of rheumatoid arthritis, they believe that genetic, environmental, and hormonal factors play a role.
 

Current pharmacological treatments for rheumatoid arthritis

Doctors commonly prescribe medications such as disease-modifying anti-rheumatic drugs (DMARDs), non-steroidal anti-inflammatory drugs (NSAIDs), analgesics, and corticosteroids. Early therapy with DMARDs has become the standard of care since it can slow the progression of the disease and induce more remissions.
Depending on the patient’s situation, doctors may prescribe DMARDs alone or in combination with other treatments. However, recent research has noted that the newer therapies of DMARDs can lead to higher risk for infections because they suppress the immune system.
 

Clinical remission is the primary goal

Despite the course of treatment, the primary goal of treating rheumatoid arthritis is to achieve clinical remission. Clinical remission is when there are no signs and symptoms of significant inflammatory activity. To achieve clinical remission, the current treatments aim to reduce inflammation and pain in the joints. Since rheumatoid arthritis is an immune-mediated disease, the medications reduce inflammation by targeting cytokines or immune cells that contribute to damaging the joints.
 
Over the last decade, treatment with biologic drugs has significantly improved disease outcomes in a significant proportion of patients with rheumatoid arthritis. The biopharmaceutical company Amgen notes this in a clinical trial statement published by ClinicalTrials.gov. However, they do note that drug-free remissions are still rare, requiring most patients to continue immunosuppressive treatments. This predisposes them to potentially serious infections.
 

A need for additional therapies with good tolerability and efficacy

Up to half of the patien ts with rheumatoid arthritis also continue to undergo symptoms of the disease. In these patients, doctors often inject glucocorticoids into the joints when single joints are inflamed. However, the duration of this treatment varies, and often, one or more joints still display signs of inflammation while inflammation in other joints has reduced.
 
Amgen has noted that there is a need for additional therapies with “good tolerability and efficacy” profiles to use in patients who still experience inflamed joints despite previous treatment. They believe that intra-articular gene therapy could be a solution to provide local treatment for those with rheumatoid arthritis.
 

Intra-articular gene therapy with new drug ART-I02

ART-I02 is an investigational new drug produced by Amgen. As a gene therapy medication, this drug expresses interferon-beta (IFN-β), a protein that has the ability to reduce the production of other proteins that play a part in the development of rheumatoid arthritis.
In pre-clinical studies, researchers found a single injection with IFN-β to be beneficial in mice and rhesus monkeys with induced arthritis. The ART-I02 drug has now moved on to a phase I clinical trial in human subjects.
 

Recruiting participants for the phase I clinical trial

Sponsored by Amgen and led by Dr. William O. Martin at the University of Calgary in Calgary, Alberta, researchers are now recruiting eligible patients with rheumatoid arthritis in the wrist to test the safety and tolerability of ART-I02. The phase I, non-randomized, open-label trial is looking to recruit a total of 15 individuals.
 
For the study, the researchers will follow a dose escalation design. They will group participants into three groups:
 
Single injection at the lowest dose
Single injection at the highest dose
Single injection at the maximum tolerated dose as assessed by the first two groups
They will start with a group of three individuals undergoing the lowest dose and three patients undergoing the highest dose. The time between dosing patients will be at least two weeks to allow for safety investigation. After the last patient is dosed in groups 1 and 2, there will be a pause of two weeks to allow for safety assessments.
 
Enrollment into the third group will only continue after a thorough assessment of safety and tolerability in the patients. They expect to enroll nine patients in the third group at the maximum tolerated dose as assessed by the first two groups.
 
The study started on January 3, 2018, and they expect to complete it by January 2020.
 
References:
ART-I02 in Patients With Rheumatoid Arthritis With Inflamed Wrists [Internet]. Clinicaltrials.gov. 2018 [cited 1 May 2018]. Available from: https://clinicaltrials.gov/ct2/show/record/NCT03445715?recrs=a&cntry=CA&draw=6&view=record
(2) Aalbers C, Bevaart L, Loiler S, de Cortie K, Wright J, Mingozzi F et al. Preclinical Potency and Biodistribution Studies of an AAV 5 Vector Expressing Human Interferon-β (ART-I02) for Local Treatment of Patients with Rheumatoid Arthritis. PLOS ONE. 2015;10(6):e0130612.
(3) Rheumatoid Arthritis: Practice Essentials, Background, Pathophysiology [Internet]. Medscape. 2018 [cited 1 May 2018]. Available from: https://emedicine.medscape.com/article/331715-overview#a2
(4) Evans C, Ghivizzani S, Robbins P. Gene Delivery to Joints by Intra-Articular Injection. Human Gene Therapy. 2018;29(1):2-14.
(5) Rheumatoid Arthritis | UCB [Internet]. UCB-Canada. 2018 [cited 1 May 2018]. Available from: https://www.ucb-canada.ca/en/Patients/Conditions/Rheumatoid-Arthritis
(6) Widdifield J, Paterson J, Bernatsky S, Tu K, Tomlinson G, Kuriya B et al. The Epidemiology of Rheumatoid Arthritis in Ontario, Canada. Arthritis & Rheumatology. 2014;66(4):786-793.
(7) Scott D, Wolfe F, Huizinga T. Rheumatoid arthritis. The Lancet. 2010;376(9746):1094-1108.