Since the company was founded, biotechnology company Kezar Life Sciences (“Kezar”) has worked to develop therapies for patients with oncologic and autoimmune disorders. Recently, they highlighted a potential treatment, KZR-616, in two poster presentations during the American College of Rheumatology Annual Meeting, or ACR Convergence 2020. According to a press release, Kezar shared data on KZR-616 and its impact on patients with systemic lupus erythematosus (SLE / “lupus”), lupus nephritis, and inflammatory myositis. You can find the poster presentations on the Kezar website.
Developed by Kezar, KZR-616 is a novel selective immunoproteasome inhibitor. It is administered subcutaneously. Normally, the immunoproteasome is stimulated or expressed when cells express some sort of inflammatory signal. However, when over expressed, researchers believe it could contribute to autoimmune disorders. By inhibiting the immunoproteasome in animal models, researchers prevented inflammation without complete immunosuppression.
In the first ACR Convergence 2020 presentation, Dr. Richard Furie, M.D., shared results from the Phase 1b MISSION clinical trial. This trial evaluated KZR-616 for patients with lupus. Some enrolled patients also had lupus nephritis, while others did not. Altogether, the trial evaluated varying doses of KZR-616 up to 75mg. Researchers evaluated the safety, efficacy, tolerability, pharmacokinetics, and pharmacodynamics. Overall, researchers found KZR-616 to be relatively safe and well-tolerated. As clinical development continues, researchers will focus on doses between 45-60mg.
In the 2nd poster presentation, Dr. Marta Del Rio Oliva, PhD, will discuss the impact of KZR-616 on mice models of inflammatory myositis. Researchers found that KZR-616 improved muscle function and protected against muscle and tissue damage. Next, researchers will use the Phase 2 PRESIDIO clinical trial to explore KZR-616 as a treatment option for patients with both forms of myositis. During the study, patients will receive either KZR-616 or a placebo. 24 patients will enroll.
While researchers are not exactly sure what causes lupus, genetics and environmental factors are believed to play a role. Lupus is an autoimmune disorder in which the body mistakenly attacks its own organs and tissue. In this case, lupus can affect organs ranging from joints and skin to heart, lungs, and blood cells. Females are more at risk of developing lupus than males. Generally, people experience symptoms between ages 15 and 45. Lupus more commonly affects patients of African-American, Hispanic, or Asian-American descent. The condition affects everyone differently, with symptoms varying in severity and development. Symptoms and complications include:
- Butterfly-shaped rashes on the center of the face
- Skin lesions that worsen with sun exposure
- Shortness of breath
- Dry eyes
- Difficulty breathing
- Chest pain
- Confusion and memory loss
- Raynaud’s phenomenon
- Organ damage
In patients with lupus nephritis, they experience kidney inflammation results from a lupus complication. Lupus nephritis impacts the parts of the kidneys that filter out waste. Nearly 50% of adult patients with lupus, and 80% of pediatric patients, will develop lupus nephritis. Symptoms include:
- Joint and muscle pain
- Butterfly-shaped rash
- Dark or foamy urine
- High blood pressure
- Swelling in the lower extremities
- Excess protein in the urine
- Kidney failure
The exact cause of myositis, or muscle inflammation, is still unknown. However, researchers believe that the condition shares common characteristics with autoimmune disorders. There are two forms of myositis: polymyositis, which causes muscle weakness, and dermatomyositis, in which a rash accompanies the muscle weakness. Other symptoms and characteristics include:
- Difficulty breathing or swallowing
- Continued muscle pain
- Rise in muscle enzyme levels
- Fatigue after standing or walking
- Difficulty climbing stairs, standing up from a seated position, or lifting arms