lupusnewstoday.com/news/intensified-dosing-of-saphnelo-seen-to-benefit-lupus-nephritis-patients/
October 16, 2023
Treatment with an intensified dosing regimen of Saphnelo (anifrolumab) led to greater improvements in kidney function compared with standard dosing or a placebo for people with active lupus nephritis, according to two-year data from the TULIP-LN clinical trial.
Lupus nephritis is a common, yet severe manifestation of lupus marked by inflammation and damage to the kidneys. The TULIP trials have tested the safety and efficacy of Saphnelo — with this study specifically focused on its use in treating individuals with systemic lupus erythematosus (SLE), commonly known as lupus, who also have lupus nephritis.
“The safety and tolerability profile through Year 2 of TULIP-LN was generally consistent with Year 1, with promising efficacy results,” the researchers wrote, adding, “Collectively, the results support further investigation of [a Saphnelo] intensified dosing regimen in larger populations of patients with active proliferative [lupus nephritis].”
Testing Saphnelo for lupus nephritis in TULIP-LN trial
Saphnelo is an antibody that targets the type 1 interferon (IFN-1) receptor, a protein involved in the inflammatory signaling cascade that’s implicated in lupus. The therapy is approved in the U.S., Canada, and Japan, and in Europe, for adults with moderate to severe lupus who are receiving standard therapy.
The IFN-1 pathway is similarly involved in lupus nephritis, a disease complication for which adequately safe and effective treatment approaches are lacking, according to the researchers.
Still, the pivotal Phase 3 trials — TULIP-1 (NCT02446912) and TULIP-2 (NCT02446899) — backing Saphnelo’s approvals excluded patients with active, severe lupus nephritis.
The Phase 2 TULIP-LN trial (NCT02547922) thus was launched to evaluate two different dosing regimens of intravenous, or into-the-vein, Saphnelo against a placebo.
The medication was given on top of standard therapies to 147 SLE patients with active lupus nephritis. Standard therapies included mycophenolate mofetil and corticosteroids.
The participants were randomly assigned to receive the standard Saphnelo regimen, which is a 300 mg monthly injection, or an intensified regimen (IR) consisting of three monthly doses of 900 mg followed by regular 300 mg injections thereafter, or a placebo.
Injections were given once every four weeks for a year, after which patients who showed any signs of having at least a partial treatment response on Saphnelo or the placebo could continue for another year.
The results from the first year of the trial indicated that although Saphnelo was well-tolerated, it did not lead to significant reductions in the urine protein to creatinine ratio (UPCR) — an indicator of kidney function — relative to the placebo. Ultimately, it failed to meet the trial’s main goal.
Still, the IR regimen was numerically superior to the placebo for a number of clinically-relevant endpoints, including corticosteroid dose declines, kidney function, and overall disease activity.
Now, scientists reported findings from the second year of the trial.
Side effects of therapy similar to that of patients without lupus nephritis
During this second year, corticosteroid doses were required to be lower than 5 mg per day by week 80, or roughly the 1.5-year mark, and remain stable until the end of the trial. Participants were required to stop treatment if their lupus nephritis worsened, steroid tapering targets were not met, or the use of prohibited immunosuppressive medications was required.
Of the participants, 101 completed the first year of the study and 75 continued into the second year. From these, 23 were on standard Saphnelo, 29 on intensified Saphnelo, and 23 on the placebo.
After two years, a numerically greater proportion of Saphnelo IR-treated patients (27.3%) attained a complete renal response (CRR) compared with those on the placebo (17.8%) or standard Saphnelo (18.6%).
A CRR is a composite measure of kidney function, defined in this trial as a 24-hour UPCR of 0.7 mg/mg or less, preserved kidney function — as measured by the estimated glomerular filtration rate (eGFR) — and no use of prohibited medications.
With other cutoff criteria for a CRR response, including a lower UPCR of 0.5 mg/mg or less, the findings continued to favor the Saphnelo IR regimen.
The proportion of patients achieving at least a partial renal response — a UPCR improvement, preserved kidney function, and no prohibited medications — after two years was nearly two times greater in those treated with Saphnelo IR compared with those given a placebo (34.1% vs 17.8%), a difference not observed with the standard regimen (23.3%).
Mean cumulative corticosteroid use was 14.2% lower in the Saphnelo IR and 16.7% lower in the standard Saphnelo groups compared with the placebo. A CRR with sustained steroid tapering was achieved by 25% of the patients in the Saphnelo IR group, by 17.8% of those on the placebo, and by 18.6% of those on the standard Saphnelo regimen.
Other outcomes, including urinary protein levels and measures of overall SLE disease activity also tended to favor Saphnelo IR.
These results support the primary analysis conclusion that [Saphnelo intensive regimen] is the dosing regimen of choice for future clinical investigations in a larger population of patients with active [lupus nephritis]
The treatment generally was found to be well-tolerated. The side effect profile was consistent with its known profile in lupus patients without active nephritis.
Altogether, while Saphnelo IR showed benefits over the placebo for most endpoints, standard Saphnelo showed responses similar to the placebo through the entire two-year period.
“As such, these results support the primary analysis conclusion that [Saphnelo] IR is the dosing regimen of choice for future clinical investigations in a larger population of patients with active [lupus nephritis],” the researchers wrote.
An ongoing Phase 3 trial, called IRIS (NCT05138133), is further evaluating the safety and efficacy of Saphnelo in lupus nephritis patients. That trial is enrolling up to 360 people, ages 18-70, with active lupus nephritis at sites globally.
