Phase 3 trial initiated to evaluate AZ's Saphnelo in lupus nephritis

The first patient has been dosed in the IRIS phase 3 trial that will evaluate AstraZeneca's (AZ) Saphnelo for the treatment of lupus nephritis. The two-year, multinational, randomised study will take place in a number of countries, enrolling adult patients diagnosed with active lupus nephritis.

The trial will involve up to 360 participants aged from 18 to 70 with active class 3 or 4 lupus nephritis. It will assess the efficacy and safety of Saphnelo, a fully human monoclonal antibody, versus placebo when combined with standard therapy.

AstraZeneca’s Saphnelo (anifrolumab) has already been approved for the treatment of moderate to severe systemic lupus erythematosus (SLE) in Europe, the US, Japan and Canada. With the recent approval, the first phase 3 trial in a potential new indiction beyond SLE has been initiated.

Mene Pangalos, executive vice president, BioPharmaceuticals R&D, AstraZeneca, said: “Lupus nephritis continues to represent a significant burden to patients worldwide. Following the approval of Saphnelo as the first new treatment for systemic lupus erythematosus in over a decade, the start of our IRIS phase 3 trial in lupus nephritis is another important step forward in our ambition to bring Saphnelo to more patients with diseases where type 1 interferon is a central driver.”

Lupus nephritis is typically characterised by kidney inflammation and is noted as one of the most common types of severe organ manifestations associated with SLE, which is a complex and chronic autoimmune disease, causing the immune system to attack health body tissue.

Patients receiving a diagnosis of lupus nephritis are placed at a higher risk of dialysis and early death, as they have been shown to have raised levels of type 1 interferons in the kidneys and blood.

Lupus nephritis is more common in women than in men, with a higher prevalence and severity of the disease among African American, Asian and Hispanic women between the ages of 15 to 44. People within these groups tend to develop the disease earlier and experience more serious complications.

Eduardo Mysler, medical director and rheumatologist at the Organización Médica de Investigación, Buenos Aires and the international coordinating investigator in the Saphnelo clinical development programme for LN, said: “The phase 2 results of anifrolumab in lupus nephritis provided important evidence suggesting that blocking type 1 interferons is a potentially promising strategy for the treatment of lupus nephritis.”

Results from the TULIP-LN1 phase 2 proof of concept, dose-finding trial of Saphnelo were published in Annals of the Rheumatic Diseases in February 2022.