With an FDA decision to come by the end of the year, Alnylam is offering a closer look at its RNA-silencing treatment for a rare kidney disorder. The drug, lumasiran, beat placebo at helping patients clear a substance called oxalate from their kidneys and lowered most patients’ oxalate levels to normal or near-normal amounts.
The updated data build on top-line results revealed in December, showing lumasiran lowered patients’ urinary oxalate levels by 54% compared with placebo and 65% compared with baseline. More than half of patients taking lumasiran reached normal levels of oxalate and 84% of them reached near-normal levels, versus no patients in the placebo group. The study was presented Sunday at the European Renal Association-European Dialysis and Transplant Association international congress.
The six-month phase 3 study pitted lumasiran against placebo in 39 patients age six or older with primary hyperoxaluria type 1, which stems from a genetic mutation causing dysfunctional enzymes in the liver.
“They have a very high level of oxalate production generated from the liver. What happens, in essence, is calcium combines with that oxalate to form calcium oxalate crystals that initially will deposit in the kidney,” Pritesh Gandhi, vice president and general manager of Alnylam’s lumasiran program, told FierceBiotech. As those crystals collect in the kidney, patients can suffer kidney stones and, eventually lose kidney function and develop end-stage kidney disease.
And that’s not all—once patients are in the throes of kidney disease, the crystals can start migrating to other parts of the body, causing vision loss in the eyes, fractures in the bones or even heart failure, Gandhi said.
Lowering patients’ oxalate levels can head off these nasty effects, for which there’s only one potential cure: a dual liver and kidney transplant. The shortage of donor organs aside, the transplant route is obviously risky, and it requires lifelong immunosuppression.
“Reducing the production of oxalate to normal, or even near-normal, levels is a very big deal in terms of potentially stopping all of the consequences of oxalate deposition and accumulation in the kidney, as well as in other organs,” Gandhi said.
Of the 26 patients who received lumasiran, 85% reported side effects, compared with 69% of the 13 placebo patients. All side effects were mild or moderate; there were no deaths or serious side effects. The most common side effect of lumasiran was injection site reaction (35%), including pain, itching or reddening of the skin. Only one patient taking lumasiran quit the study because of side effects.
Alnylam has filed lumasiran for approval in the U.S. and Europe, with the FDA expected to make a decision by Dec. 3. The company hopes to launch the drug toward the end of the year.
Beyond this trial, Illuminate-A—which studied lumasiran in patients who have preserved kidney function—Alnylam is testing the drug in two other phase 3 trials to gauge its effects on different stages of the disease. One study is looking at patients younger than six years old, including infants, while the other is studying older patients with more advanced disease who may depend on dialysis.