Findings from the pivotal section 3 ILLUMINATE-A trial of lumasiran (Oxlumo) in sufferers with main hyperoxaluria sort 1 (PH1) have now been printed within the New England Journal of Medication (NEJM).1,2
ILLUMINATE-A was considered one of two trials that supported the November 2020 FDA approval of lumasiran as the primary drug for the therapy of sufferers with PH1.3 The drug is authorised for each grownup and pediatric sufferers.
“PH1 usually presents in formative years, with kidney stones, nephrocalcinosis, renal failure and, in superior phases, systemic unfold of oxalate all through the physique with life-threatening penalties. Oxalate drives illness manifestations and development, and is the poisonous mediator of end-organ injury in PH1,” Yaacov Frishberg, MD, head of the Division of Pediatric Nephrology, Shaare Zedek Medical Heart, Jerusalem, Israel, and lead co-author on ILLUMINATE-A, said in a press launch.
“We consider the publication of the ILLUMINATE-A Section 3 examine ends in the NEJM is a testomony to lumasiran as an oxalate-lowering remedy which is anticipated to confer important medical profit to youngsters and adults residing with this illness,” added Frishberg.
The section 3 open-label ILLUMINATE-A trial (NCT03681184) included 39 sufferers aged ≥6 years with PH1. Total, 26 sufferers have been randomized to lumasiran and 13 have been randomized to placebo.
Affected person traits have been thought of by the investigators to be typically nicely balanced between the two examine arms. At baseline, the median age throughout all sufferers was 14 years (vary, 6-60), 85% of sufferers had a historical past of kidney-stone occasions, and 54% of sufferers had a historical past of nephrocalcinosis.
Within the therapy arm, sufferers obtained subcutaneous lumasiran month-to-month for 3 months adopted by quarterly upkeep doses at 3 mg/kg. The first end result measure was the % change in 24-hour urinary oxalate excretion from baseline to month 6.
“We discovered that the share discount in 24-hour urinary oxalate excretion was 53.5 share factors larger with lumasiran than with placebo through the 6-month double-blind therapy interval and that almost all sufferers who obtained lumasiran had regular or near-normal urinary oxalate ranges at month 6,” the authors wrote of their NEJM manuscript.
Amongst sufferers within the lumasiran arm, there was a 65.4% common discount of oxalate within the urine in contrast with a median discount of 11.8% within the placebo arm. Over half (52%) of sufferers receiving lumasiran achieved a traditional 24-hour urinary oxalate stage at 6 months, in contrast with no sufferers within the placebo group. Eighty-four % of sufferers within the lumasiran arm reached regular or near-normal urinary oxalate ranges versus no sufferers within the placebo arm.
Concerning security, the investigators decided that lumasiran was secure and tolerable. No extreme or severe opposed occasions (AEs) have been reported and there have been no affected person deaths. All AEs have been gentle to average. The most typical AE with lumasiran was injection web site response, which occurred in 38% of sufferers.
1. Alnylam Proclaims Publication of ILLUMINATE-A Section 3 Research Outcomes for Lumasiran in The New England Journal of Medication. Revealed on-line March 31, 2021. Accessed April 1, 2021. https://bit.ly/3wdZNh7.
2. Garrelfs SF, Frishberg Y, Hulton SA, et al. Lumasiran, an RNAi therapeutic for main hyperoxaluria sort 1. N Engl J Med. 2021;384(13):1216-1226. doi: 10.1056/NEJMoa2021712
3. FDA Approves First Drug to Deal with Uncommon Metabolic Dysfunction. Revealed on-line November 23, 2020. https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-treat-rare-metabolic-disorder. Accessed April 1, 2020.