New Medicines

Primary hyperoxaluria


New molecular entity
Alnylam Pharmaceuticals
Alnylam Pharmaceuticals

Development and Regulatory status

Pre-registration (Filed)
Pre-registration (Filed)
Pre-registration (Filed)
Apr 20 · Filed in EU via centralised procedure [7].
Jan 20 · Alnylam has initiated a rolling submission of its new drug application to the FDA for lumasiran for the treatment of primary hyperoxaluria type 1 [8].
Nov 19 · Alnylam announces an intention to file in EU and US early in 2020 if results from ILLUMINATE-A are positive [6].
Oct 18 · In October 2018, the PIII ILLUMINATE-A trial in children, aged 6 years and older, and adults with primary hyperoxaluria type 1 started (NCT03681184; EudraCT2018-001981-40).
Mar 18 · Lumasiran granted Breakthrough Therapy Designation (BTD) by the US FDA for treatment of primary hyperoxaluria Type 1 (PH1). Alnylam announced plans to rapidly advance lumasiran into a PIII pivotal study in late 2018, and to commercialise lumasiran globally, assuming product approval.[3]
Mar 18 · the CHMP granted EMA PRIME (Priority Medicine) status to lumasiran at their March 18 meeting [4].
Mar 16 · Orphan drug designation granted to lumasiran for treatment of primary hyperoxaluria I by the EMA
Feb 16 · US FDA granted an orphan drug designation to lumasiran for treatment of primary hyperoxaluria I


Metabolic disorders (09.08)
Silences the gene for glycolate oxidase to starve the pathway of oxalate production and prevent its associated pathology.[2,3]
One estimate places the prevalence of PH type I at 1-3 cases per 1,000,000 people in the general population and the incidence at 1 case per 120,000 live births per year in Europe.[1]
Primary hyperoxaluria
type 1 (PH1)
Subcutaneous injection

Trial or other data

Dec 19 · Positive topline PIII results announched from the randomised, double-blind, placebo-controlled, ILLUMINATE-A trial (NCT03681184). Pts (n=30) were randomised 2:1 to lumasiran 3mg/kg/month for 3m the quarterly or placebo. The primary endpoint, % change from baseline in 24-hour urinary oxalate excretion, was met at 6m in the lumasiran gp (p<0.0001). There were no serious adverse events and limasiran was generally well-tolerated.[7]
Nov 19 · PIII trial ILLUMINATE-C starts, it will enrol patients of all ages with advanced renal disease, and the primary study endpoint is the percent reduction in plasma oxalate from baseline to six months. Results expected late 2020 [5]. 11/11/2019 13:56:10
Nov 17 · Alnylam released positive preliminary from Part B of an ongoing PI/II trial. In the first two cohorts of pts with primary hyperoxaluria type 1 (PH1) (6 - 19 years old) dosed with lumasiran or placebo (n = 8), achieved substantial reductions in urinary oxalate levels. Specifically, 3 pts in the first cohort, receiving monthly s.c. doses of lumasiran 1 mg/kg for 3 months, experienced > 50% decreases in urinary oxalate excretion vs. baseline as compared with the 1 pt in placebo arm. The placebo patient in the first cohort experienced a similar reduction in urinary oxalate when lumasiran 1 mg/kg was administered monthly for 3 months. All 4 pts in this initial low dose cohort showed a 66% mean maximal reduction in urinary oxalate, and all achieved urinary oxalate levels at or near the normal range. Furthermore, lumasiran reduced urinary oxalate excretion below 1.1 mmol/24hrs/1.73m2 in all pts with baseline excretion ≥ 1.6 mmol/24hrs/1.73m2 (n = 3). Aggregate data (n = 4) from Cohort 2 (monthly does of lumasiran 3 mg/kg or placebo for 3 months) demonstrated a mean reduction of 47% in urinary oxalate output vs. baseline after the first of 3 doses. Lumasiran achieved dose-dependent and statistically significant increase in plasma and urine glycolate from baseline vs. placebo, with upto an 8-fold increase in plasma glycolate in the highest dose cohort. The effects of lumasiran were highly durable, with levels sustained through 85 days at the highest dose, supportive of a once-monthly and possibly once-quarterly subcutaneous dose regimen. Lumasiran was well tolerated with no treatment-related serious adverse events (SAEs) or study discontinuations up to seven months from initial dosing. In all patients, lumasiran was well tolerated and a mild and transient injection site reaction was reported as a drug-related AE. Five SAEs were reported in three patients, including two episodes of renal stones and a case of pyelonephritis in a patient during placebo dosing. The two remaining SAEs reported were renal stones and dehydration associated with gastroenteritis, both of which occurred after dosing with lumasiran but were not considered drug-related.[2,3]
Oct 17 · Alnylam initiated PII extension trial to evaluate the long-term safety of multiple doses of lumasiran SC injection in pts with primary hyperoxaluria type 1 and who completed Study ALN-GO1-001 (ALN-GO1-002; EudraCT2016-003134-24). The open-label trial is recruiting 20 pts in France, and will extend to Germany, Israel, Jordan, the Netherlands, the US, the UAE and the UK.[2]
Mar 16 · Initiation of a randomised two-part PI/II trial (ALN-GO1-001; EudraCT2015-004407-23; NCT02706886)to evaluate safety and tolerability of single and multiple sc doses of lumasiran. The part A evaluated a single dose of lumasiran in 32 healthy volunteers and part B is a multi-dose study designed to enrol ~24 pts with primary hyperoxaluria type 1. The trial intends to enrol ~60 pts, aged 6 to 64 years, in the US, Israel, France, the Netherlands, Germany and the UK.[2]

Evidence based evaluations