Megan Clowse, M.D.: How Dapirolizumab Pegol Could Change the Future of Lupus Treatment

Megan Clowse, M.D., M.P.H.

Credit: Duke University School of Medicine

In an interview with The Educated Patient, Megan Clowse, M.D., M.P.H., associate professor of medicine and chief of the Division of Rheumatology and Immunology at Duke University School of Medicine, discusses results from the PHOENYCS GO study, a 48-week clinical trial that evaluated treatment with dapirolizumab pegol (DZP) in patients with moderate to severe lupus who continued to have active or frequently flaring symptoms despite their usual medications.

Patients aged 16 and older were randomly assigned to receive either an intravenous dose of the experimental drug DZP every 4 weeks along with their usual medications or a placebo along with their usual medications. The main goal of the study was to see whether the drug, combined with standard medications, could improve lupus symptoms at 48 weeks. Other goals included assessing whether the drug could reduce the number of severe flares and measure other improvements in symptoms.

Results were presented at the American College of Rheumatology (ACR) Convergence 2024.

What were the main findings of this study, and what do they mean for people living with systemic lupus erythematosus (SLE)?

Megan Clowse, M.D, M.P.H.: This phase three study successfully met its primary end point. We were aiming to demonstrate that dapirolizumab pegol (DZP) could reduce lupus disease activity, and this was confirmed after 48 weeks. By the end of the study, we saw a clear and statistically significant improvement in lupus activity among those on the drug compared with the placebo group.

People living with lupus are a unique population. The disease primarily affects young women — 90% of lupus patients are female, often diagnosed in their teens, 20s or 30s. This means they're living with a chronic illness for a long time, impacting daily life with symptoms like inflammation in the kidneys, joints and skin, alongside chronic fatigue and pain. The disease significantly decreases quality of life, creating an unmet need to both control inflammation and improve overall well-being.

Many patients are on complex medication regimens, often involving multiple daily doses of drugs like steroids and immunosuppressants. Prednisone, a common corticosteroid, is particularly effective for quick relief of symptoms, but it carries significant long-term risks such as cardiovascular problems, high blood pressure, diabetes and osteoporosis.

One key finding of this study is that DZP helps manage inflammation — reducing arthritis, skin involvement and other symptoms — even as patients taper off steroids. We saw that it's possible to reduce steroid use without worsening symptoms, a crucial balance. Although we're not sharing detailed data yet on fatigue and pain, the findings hint at potential improvements in these areas as well.

What are some of the current unmet needs in treating SLE that this drug aims to address?

MC: One of the biggest challenges is the current treatment regimen, which often involves numerous oral medications. This new drug, delivered as a monthly intravenous infusion, could significantly reduce the pill burden for patients, potentially minimizing the number of medications they need in the long term. Additionally, DZP shows promise in directly targeting inflammation and helping patients feel better in their day-to-day lives.

You mentioned future research on pain and fatigue. What are the next steps for your team?

MC: Yes, we have several next steps. Based on the positive results of this study, we are launching a second phase three trial, which is required for FDA approval. We're also conducting a long-term study for patients who have already received the drug, allowing us to track both its benefits and any potential safety risks over an extended period.

We have collected a wealth of data, including patient-reported outcomes on fatigue, pain and emotional well-being, as well as doctors' assessments of disease activity and various biomarkers. We're excited to delve deeper into this data to identify which aspects of the disease DZP targets most effectively. This will help ensure that we deliver the treatment to the right patients.

Is there anything else you'd like our audience to know from a patient perspective?

MC: I hope patients find encouragement in the results of this study and realize that there are effective treatments available to help manage lupus and improve quality of life. Working closely with a rheumatologist can optimize a treatment plan, allowing for a more productive and less painful life. It can be challenging to find the right combination of therapies, but I’m optimistic that DZP will become a valuable addition to our treatment options, providing more hope and relief for patients.

This transcript was edited for clarity.