Alnylam Posts Positive Results of Groundbreaking Phase III PH1 Trial

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Alnilam – the bright center star in the middle of Orion’s belt – has navigated its namesake Alnylam to positive results in their ILLUMINATE-B Phase III clinical trial evaluating RNAi therapeutic, lumasiran, in young children with Primary hyperoxaluria Type 1 (PH1).

PH1 is a rare, hereditary condition causing recurrent kidney and bladder stones due to the overproduction of oxalate by the liver. The condition often leads to end-stage renal disease (ESRD), a life-threatening condition that prevents the kidneys from effectively filtering fluids and waste. PH1 affects an estimated 1 in 58,000 individuals worldwide.

Lumasiran is designed to lower the level of oxalate in the body by reducing the levels of an enzyme called glycolate oxidase, which depletes the substrate necessary for oxalate production.

The topline results of ILLUMINATE-B, a single-arm, 18-subject study, indicated a clinically meaningful reduction in urinary oxalate excretion, with a safety profile matching that of ILLUMINATE-A, a study evaluating lumasiran in older children and adults.

ILLUMINATE-B is the first ever to study the safety and efficacy of RNAi therapeutics in children under the age of six, and infants as young as four months.

Pritesh J. Gandhi, Vice President and General Manager of Alnylam’s Lumasiran Program, is hopeful that the results may provide a better quality of life for these young patients.

“The only curative option for this particular population is a liver transplant, and you talk about less than six-year-olds getting a liver, you have to get the right size, you have to get a match, the patients have to go through chronic immunosuppressant therapy. I mean, it’s a big deal,” Gandhi told BioSpace.  “So, what lumasiran does of course is to try and imagine averting all of that in the future, changing the current practice in terms of what the standard of care would look like for this particular patient population.”

With lumasiran, the goal is to make PH1 a condition that patients can live with, with the minimum of lifestyle disruption. 

“Patients would have to take the drug chronically,” Gandhi said. “As they start to age over time, they would require a dose that would be administered on a quarterly basis...and that would be a lifetime therapy.”

Complete ILLUMINATE-B Phase III results will be presented virtually on October 22nd at the American Society of Nephrology (ASN) Kidney Week. 

The Alnylam Lumasiran Program is comprehensive, aiming to address the disease across all patient populations. Topline Phase III results from ILLUMINATE-C, a study assessing lumasiran in PH1 patients of all ages with advanced renal disease, are expected in late 2021.

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