1st patient enrolled in global Phase 2 trial of daxdilimab for lupus

Study to test safety, efficacy of Horizon's lupus nephritis treatment

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by Steve Bryson PhD |

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A Phase 2 trial evaluating the safety and efficacy of daxdilimab, a potentially first-in-class treatment for people with active, proliferative lupus nephritis (LN) — a lupus complication marked by kidney damage — has enrolled its first patient.

Horizon Therapeutics, the therapy’s developer, anticipates about 210 patients, ages 18–80, will enroll in the global study (NCT05540665), expected to span more than two years.

Recruitment is ongoing at sites in the U.S., Argentina, Brazil, Israel, Malaysia, Poland, Serbia, Spain, Taiwan, and Thailand. More information about contacts and locations is available on the trial page.

“For individuals living with LN, evaluating a safe and effective treatment that can prevent worsening kidney damage and decrease the risk of kidney failure and end-stage renal disease is a key objective,” Kenneth Kalunian, MD, a professor of medicine at the University of California, San Diego, said in a company press release.

“Current treatment regimens include intensive immunosuppressive therapy that can be associated with several adverse events,” Kalunian said, adding, “There is a need to identify a more specific medicine for those with proliferative LN.”

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Treatment candidate for lupus nephritis aims to stop inflammation

LN is a potentially life-threatening complication characterized by inflammation in the kidneys. Proliferative forms of LN are associated with a higher risk of progression to end-stage kidney disease, requiring dialysis or, potentially, a kidney transplant. The condition is most prevalent in certain ethnic groups, including African American, Asian, and Hispanic populations.

Inflammatory responses in people with systemic lupus erythematosus (SLE), including those with kidney involvement, are associated with a group of immune signaling molecules called interferons.

Daxdilimab is designed to deplete plasmacytoid dendritic cells (pDCs), a type of immune cell that releases high levels of interferons. Its goal is to interrupt the cycle of inflammation that causes tissue damage in LN.

Lupus nephritis “is a serious manifestation of SLE and requires urgent treatment to avoid chronic kidney disease, dialysis or kidney transplantation,” said Theresa Podrebarac, MD, Horizon’s senior vice president of clinical development.

“Early studies point to the role of plasmacytoid dendritic cells (pDCs) and type 1 interferons in its pathogenesis [disease mechanisms],” Podrebarac said.

To be eligible to participate in the Phase 2 study, patients must have received a diagnosis of proliferative LN based on a kidney biopsy within six months of the study’s start. Additionally, they must show signs of impaired kidney function in several standard tests.

Following enrollment, participants will be randomly assigned to receive daxdilimab or a placebo. Both will be given by an under-the-skin (subcutaneous) injection for 52 weeks, or one year, in addition to their standard of care background therapy. All patients will then be assigned to a quarterly maintenance regimen of either daxdilimab or placebo for a second year, based on kidney responses during the first year.

The study’s main goal is to determine the proportion of participants achieving a complete renal response (CRR) at week 48 and sustained through to week 52. CRR is a composite measure defined by preservation or improvement of kidney function, and a reduction of protein in the urine — a classical sign of kidney damage.

In addition to safety, secondary efficacy outcomes include assessing the proportion of patients achieving an overall renal response, meaning the proportion of those attaining CRR or a partial kidney response.

Changes in estimated glomerular filtration rate (eGFR), a standard kidney function measure, also will be assessed, and the trial will determine the proportion of patients who able to sustainably reduce the use of oral corticosteroids.

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Phase 2 Trial Tests Daxdilimab as Potential DLE Therapy

Testing daxdilimab for other types of lupus

Horizon also is developing daxdilimab for patients with discoid lupus erythematosus, known as DLE, which is a form of lupus affecting the skin.

Earlier this year, the company enrolled its first patient in RECAST DLE (NCT05591222), a Phase 2 study testing daxdilimab in patients with moderate-to-severe DLE. That trial aims to enroll about 100 DLE patients, ages 18-75, whose disease is unresponsive to current treatments.

Meanwhile, the ongoing Phase 2 RECAST SLE trial (NCT04925934) is investigating daxdilimab’s ability to reduce corticosteroid use in 214 people with moderate to severely active SLE.

“As a part of our commitment to addressing better treatment options for autoimmune diseases, we are currently evaluating daxdilimab in SLE as well as a variety of other conditions,” Podrebarac said.