Investigational Immunotherapy Shows Promise Treating Lupus

Celgene recently announced positive results from a phase 2a clinical trial of an experimental immunotherapy, CC-220, in the treatment of lupus at the Annual European Congress of Rheumatology.

CC-220 is an investigational immunomodulatory drug that binds to and modulates cereblon, which is a component of the E3 ubiquitin ligase complex, Celgene reported. The drug is thought to reduce levels of Ikaros and Aiolos transcription factors that increase the risk of lupus.

The investigators found that treatment with CC-220 improved multiple measures of disease activity in patients with systemic lupus erythematosus compared with placebo.

"While the outlook for patients with lupus has improved over the last 75 years, treatment options remain limited," said Richard Furie, MD, chief of Rheumatology at Northwell Health in New York. "New treatment options are greatly needed for people who are dealing with this often disabling autoimmune condition."

Included in the SLE-001 clinical trial were 42 patients diagnosed with lupus at least 6 months prior to the start. All patients included had a baseline SELENA-SLEDAI score of at least 4.

Patients were randomized to receive CC-220 0.3-mg every other day, 0.3-mg once daily, 0.3-mg alternating with 0.6-mg once daily, 0.6-mg once daily, or placebo for 12 weeks, according to the study. After 12 weeks, patients underwent another 12 weeks of observation or long-term extension.

The investigators evaluated the safety, efficacy, and pharmacokinetics of CC-220. For efficacy, they evaluated changes in Cutaneous Lupus Area and Severity Activity Index (CLASI) and SELENA-SLEDAI score, which examines lupus disease activity across 24 different factors.

After 85 days of treatment, the investigators found that disease activity specific to the skin (measured by CLASI) was reduced by -4.3 to -7.8 among patients treated with CC-220, while the CLASI score increased 0.4 among placebo patients, according to the study. These results were significant, since the reductions in CLASI were higher than the minimal clinically important difference of -4.

Patients treated with CC-220 were also observed to have an at least 4-point reduction in SELENA-SLEDAI score, with a range between 22.2% and 50%; however, patients treated with placebo only saw a 12.5% reduction in the score, according to the press release.

The investigators also found that patients treated with CC-220 had a greater improvement in tender joint count and swollen joint count compared with placebo, according to the study. They also found that patients in the treatment groups also had an improvement in the Physician’s Global Assessment score, while placebo patients were not observed to improve.

The authors reported that common adverse events included nausea, diarrhea, and maculopapular rash. Serious pneumonia was reported among 2 patients receiving the highest doses of CC-220 and 2 patients from the placebo group. Overall, 6 patients discontinued due to adverse events, according to Celgene.

"Celgene is committed to addressing immunological diseases with serious unmet needs and investigating compounds that we believe could have the potential to improve the lives of patients. We're excited by the possibility that CC-220 may offer a novel mechanism to address lupus, a complex disease that has few effective treatment options," said Terrie Curran, president, Celgene Inflammation & Immunology. "Our work with CC-220 will also help to diversify and deepen our Inflammation and Immunology franchise as we continue to advance CC-220 in the clinic."