dm+d

Unassigned

New Medicines

OxlumoPrimary hyperoxaluria

Information

Oxlumo
New molecular entity
Alnylam Pharmaceuticals
Alnylam Pharmaceuticals

Development and Regulatory status

Approved (Licensed)
Approved (Licensed)
Approved (Licensed)
Yes
Yes
Jun 21 NICE announces that following on from a request from the company, the timelines for its evaluation have revised. It is now anticipated to begin in early November 2021, with the deadline for submissions expected in approximately mid-January 2022. No revised publication date given [19].
Jan 21NICE announces that following on from a request received from the company, the timelines for its evaluation have been revised and it is now anticipated to begin in mid-May 2021. Publication of this topic is expected to be in mid-March 2022. Consequently it is anticipated that this will affect UK launch plans [17].
Nov 20Approved in US. [17]
Nov 20Approved in EU [16].
Oct 20Recommended for EU approval by CHMP - the full indication is "Treatment of primary hyperoxaluria type 1 (PH1) in all age groups." The medicine should be initiated and supervised by physicians experienced in the management of hyperoxaluria. [14]
Jul 20Granted Early Access to Medicines Status (EAMS) in UK for treatment of primary hyperoxaluria type 1 (PH1) in all age groups [12].
May 20Granted priority review by FDA, with a target action date of 3/12/20[10].
Apr 20Filed in EU via centralised procedure [7].
Jan 20Alnylam 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 19Alnylam announces an intention to file in EU and US early in 2020 if results from ILLUMINATE-A are positive [6].
Oct 18In 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 18Lumasiran 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 18the CHMP granted EMA PRIME (Priority Medicine) status to lumasiran at their March 18 meeting [4].
Mar 16Orphan drug designation granted to lumasiran for treatment of primary hyperoxaluria I by the EMA
Feb 16US FDA granted an orphan drug designation to lumasiran for treatment of primary hyperoxaluria I

Category

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

Further information

Yes
To be confirmed

Trial or other data

Jul 21Alnylam report positive results from PIII ILLUMINATE-C study of lumasiran in patients with advanced PH1 and severe renal impairment (eGFR ≤ 45 mL/min/1.73m2 or elevated serum creatinine for patients <12 months of age). Alnylam intend to file supplemental applications to US FDA and EMA H2 21 [20].
Apr 21Results of PIII ILLUMINATE-A trial reported in NEJM [18].
Oct 20Top-line PIII data from the ILLUMINATE-B trial in children aged <6 years show that lumasiran is linked to a “clinically significant” decline in oxalate levels in children with primary hyperoxaluria type 1. Full data will be announced in Oct 20. The company is also conducting teh PIII ILLUMINATE-C study of lumasiran in PH1 pts of all ages with advanced renal disease, including on dialysis, with results expected in 2021.[13]
Jun 20More detailed PIII data from the ILLUMINATE-A trial of lumasiran for treatment of PH1 presented at the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) International Congress. Lumasiran hit the primary endpoint with a 53.5% mean reduction in urinary oxalate vs. placebo. It also demonstrated a 65.4% mean reduction in urinary oxalate relative to baseline. [11]
Dec 19Positive 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 19PIII 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 17Alnylam 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 17Alnylam 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 16Initiation 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