Mar 31, 2021 Press Release for Alnylam
Alnylam Announces Publication of ILLUMINATE-A Phase 3 Study Results for Lumasiran in The New England Journal of Medicine
Mar 31, 2021
- ILLUMINATE-A Phase 3 Study Evaluated the Efficacy and Safety of Lumasiran in Adult and Pediatric Patients with Primary Hyperoxaluria Type 1 (PH1) -
- Lumasiran Demonstrated a Clinically Significant Reduction in Urinary Oxalate, a Primary Determinant of Progression to Renal Failure in PH1, Compared to Placebo -
- Manuscript Marks the Tenth Publication of Clinical Trial Results for Alnylam Programs in
The data reported in the ILLUMINATE-A Phase 3 study publication demonstrated that RNAi-mediated targeting of liver GO by lumasiran led to substantial and sustained reductions in urinary oxalate—the toxic metabolite responsible for the debilitating and life-threatening clinical manifestations of PH1. Relative to placebo, treatment with lumasiran resulted in a clinically significant (53.5 percent) reduction in 24-hour urinary oxalate excretion from baseline to month 6 – the primary endpoint of the study.
Improvements were also observed in a number of secondary endpoints, including the proportion of patients achieving normala or near-normalb levels of urinary oxalate, with 84 percent of lumasiran-treated patients meeting this endpoint compared with no patients (0 percent) on placebo. Patients treated with lumasiran also experienced favorable effects on exploratory endpoints related to nephrocalcinosis and the rate of renal stone eventsc compared with placebo.
Lumasiran administration was associated with an encouraging safety and tolerability profile, with no serious or severe adverse events (AEs). The most common AEs that occurred more frequently with lumasiran than placebo were injection site reactions (38 versus 0 percent). All injection site reactions were mild and transient and did not result in discontinuation of treatment.
“PH1 often presents in early life, with kidney stones, nephrocalcinosis, renal failure and, in advanced stages, systemic spread of oxalate throughout the body with life-threatening consequences. Oxalate drives disease manifestations and progression, and is the toxic mediator of end-organ damage in PH1,” said Prof.
“Publication of the ILLUMINATE-A results in NEJM is an exciting achievement, highlighting the tremendous unmet need for novel therapies for this devastating disease and the role lumasiran is playing to fill this need. We are thrilled by the fact that this is now the tenth publication in NEJM on results from clinical studies of Alnylam’s RNAi therapeutics, a noteworthy milestone underscoring the impact of RNAi on clinical research and the practice of medicine,” said
A total of 38d of 39 patients completed the ILLUMINATE-A 6-month primary analysis period and all eligible patients transitioned to the study extension period. Results from the 12-Month extension period were presented at the
IMPORTANT SAFETY INFORMATION
Adverse Reactions
The most common adverse reaction that occurred in patients treated with OXLUMO was injection site reaction (38%). Symptoms included erythema, pain, pruritus, and swelling.
Pregnancy and Lactation
No data are available on the use of OXLUMO in pregnant women. No data are available on the presence of OXLUMO in human milk or its effects on breastfed infants or milk production. Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for OXLUMO and any potential adverse effects on the breastfed child from OXLUMO or the underlying maternal condition.
For additional information about OXLUMO, please see the full Prescribing Information.
About OXLUMO™ (lumasiran)
OXLUMO is an RNAi therapeutic targeting hydroxyacid oxidase 1 (HAO1) for the treatment of primary hyperoxaluria type 1 (PH1) to lower urinary oxalate levels in pediatric and adult patients. HAO1 encodes glycolate oxidase (GO), an enzyme upstream of the disease-causing defect in PH1. OXLUMO works by degrading HAO1 messenger RNA and reducing the synthesis of GO, which inhibits hepatic production of oxalate – the toxic metabolite responsible for the clinical manifestations of PH1. In the pivotal ILLUMINATE-A study, OXLUMO was shown to significantly reduce levels of urinary oxalate relative to placebo, with the majority of patients reaching normal or near-normal levels. Injection site reactions (ISRs) were the most common drug-related adverse reaction. In the ILLUMINATE-B pediatric Phase 3 study, OXLUMO demonstrated an efficacy and safety profile consistent to that observed in ILLUMINATE-A. OXLUMO utilizes Alnylam’s Enhanced Stabilization Chemistry (ESC)-GalNAc conjugate technology designed to increase potency and durability. OXLUMO is administered via subcutaneous injection once monthly for three months, then once quarterly thereafter at a dose based on actual body weight. For patients who weigh less than 10 kg, ongoing dosing remains monthly. OXLUMO should be administered by a healthcare professional. For more information about OXLUMO, visit OXLUMO.com.
About ILLUMINATE-A Phase 3 Study
ILLUMINATE-A (NCT03681184) is a six-month randomized, double-blind, placebo-controlled, global, multicenter Phase 3 study (with a 54-month extension period) to evaluate the efficacy and safety of lumasiran in 39 patients, age six and older, with a documented diagnosis of PH1. Patients were randomized 2:1 to receive three monthly doses of lumasiran or placebo followed by quarterly doses at 3 mg/kg. The primary endpoint was the percent change in 24-hour urinary oxalate excretion from baseline to the average of months 3 to 6 in the patients treated with lumasiran as compared to placebo. Treatment arms were stratified at randomization based upon mean 24-hour urinary oxalate during screening (≤1.7 or >1.7 mmol/24hr/1.73m2). Key secondary and exploratory endpoints were designed to evaluate additional measures of urinary oxalate, plasma oxalate, estimated glomerular filtration rate (eGFR), nephrocalcinosis, renal stone events, safety and tolerability.
About Primary Hyperoxaluria Type 1 (PH1)
PH1 is an ultra-rare genetic disease that affects an estimated one to three individuals per million in
About RNAi
RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine. By harnessing the natural biological process of RNAi occurring in our cells, a new class of medicines, known as RNAi therapeutics, is now a reality. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise
About
Alnylam Forward Looking Statements
Various statements in this release concerning
Footnotes:
a Normal is defined as urinary oxalate levels at or below the upper limit of normal (ULN; ≤ 0.514 mmol/24 hr/1.73 m2); b near-normal is defined as urinary oxalate levels at or below 1.5 x ULN (≤ 0.771 mmol/24 hr/1.73 m2); ca renal stone event was defined as an event which includes at least one of the following: visit to healthcare provider because of a renal stone, medication for renal colic, stone passage, macroscopic hematuria due to a renal stone; done patient discontinued study drug after receiving a single dose and withdrew from the study after Month 3. Parent/guardian stopped participation due to patient's inability to comply with protocol-specific testing.
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