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Initial 1-year data sustain lumasiran efficacy in PH1


Treatment with lumasiran (Oxlumo) for 12 months was linked to improvement in nephrocalcinosis in one or both kidneys in patients with primary hyperoxaluria type 1 (PH1), according to early results of a 1-year analysis of the pivotal phase 3 ILLUMINATE-A trial.1

The early findings included data from 24 patients in ILLUMINATE-A who had received 12 months of lumasiran and had valid renal ultrasounds at baseline. An improvement in nephrocalcinosis grade from baseline occurred in almost half (46%; n = 11) of these patients, with another 4 patients (17%) remaining stable. In 3 patients (13%) nephrocalcinosis grade became worse, and 6 patients (25%) had not received a 12-month ultrasound at the time of the analysis.

There were 14 evaluable patients who had nephrocalcinosis at baseline. Eleven (79%) of these patients demonstrated an improvement in nephrocalcinosis grade over baseline at the 12-month analysis. Further, 73% (n = 8) of these patients experienced improvement in both kidneys.

ILLUMINATE-A was one of two trials that supported the November 2020 FDA approval of lumasiran as the first drug for the treatment of patients with PH1.2 The drug is approved for both adult and pediatric patients.

“Nephrocalcinosis is a key indicator of disease severity in PH1,” Jeffrey M. Saland, MD, professor and chief, Pediatric Nephrology and Hypertension, Jack and Lucy Clark Department of Pediatrics, Mount Sinai Kravis Children’s Hospital, New York City and investigator on the ILLUMINATE-A trial, stated in a press release. “Thus, unilateral and bilateral improvements in nephrocalcinosis in some patients treated with Oxlumo are a welcome observation and are consistent with our expectation of the potential clinical impact of a sustained and substantial reduction in urinary oxalate levels.”

Data from the 6-month analysis of the ILLUMINATE-A trial were recently published in the New England Journal of Medicine (NEJM).3,4 The phase 3 open-label ILLUMINATE-A trial (NCT03681184) included 39 patients aged ≥6 years with PH1. Overall, 26 patients were randomized to lumasiran and 13 were randomized to placebo.

Patient characteristics were considered by the investigators to be generally well balanced between the 2 study arms. At baseline, the median age across all patients was 14 years (range, 6-60), 85% of patients had a history of kidney-stone events, and 54% of patients had a history of nephrocalcinosis.

In the treatment arm, patients received subcutaneous lumasiran monthly for 3 months followed by quarterly maintenance doses at 3 mg/kg. The primary outcome measure was the percent change in 24-hour urinary oxalate excretion from baseline to month 6.

“We found that the percentage reduction in 24-hour urinary oxalate excretion was 53.5 percentage points greater with lumasiran than with placebo during the 6-month double-blind treatment period and that most patients who received lumasiran had normal or near-normal urinary oxalate levels at month 6,” the authors wrote in their NEJM manuscript.

Among patients in the lumasiran arm, there was a 65.4% average reduction of oxalate in the urine compared with an average reduction of 11.8% in the placebo arm. Over half (52%) of patients receiving lumasiran achieved a normal 24-hour urinary oxalate level at 6 months, compared with no patients in the placebo group. Eighty-four percent of patients in the lumasiran arm reached normal or near-normal urinary oxalate levels versus no patients in the placebo arm.

Regarding safety, the investigators determined that lumasiran was safe and tolerable. No severe or serious adverse events (AEs) were reported and there were no patient deaths. All AEs were mild to moderate. The most common AE with lumasiran was injection site reaction, which occurred in 38% of patients.


1. Alnylam Announces Positive Early Results on Clinical Outcome Measures from ILLUMINATE-A Phase 3 Study of OXLUMO® (lumasiran).Published online May 3, 2021. Accessed May 3, 2021. https://bit.ly/3xFHYIx.

2. FDA Approves First Drug to Treat Rare Metabolic Disorder. Published online November 23, 2020. https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-treat-rare-metabolic-disorder. Accessed April 1, 2020.

3. Alnylam Announces Publication of ILLUMINATE-A Phase 3 Study Results for Lumasiran in The New England Journal of Medicine. Published online March 31, 2021. Accessed April 1, 2021. https://bit.ly/3wdZNh7.

4. Garrelfs SF, Frishberg Y, Hulton SA, et al. Lumasiran, an RNAi therapeutic for primary hyperoxaluria type 1. N Engl J Med. 2021;384(13):1216-1226. doi: 10.1056/NEJMoa2021712

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