FDA Expands Approval of Alnylam’s Oxlumo to Include Advanced PH1

The U.S. Food and Drug Administration granted Alnylam Pharmaceuticals expanded approval of Oxlumo to include the treatment of primary hyperoxaluria type 1 (PH1) to lower urinary oxalate (UOx) and plasma oxalate (POx) levels in pediatric and adult patients.

PH1 is an ultra-rare genetic disease characterized by oxalate overproduction in the liver. The excess production of oxalate results in the deposition of calcium oxalate crystals in the kidneys and urinary tract and can lead to the formation of painful and recurrent kidney stones and nephrocalcinosis, which can progress to kidney failure. PH1 can also lead to oxalate deposition in multiple organs beyond the kidney, a condition known as systemic oxalosis.

Oxlumo is an RNAi therapeutic targeting hydroxyacid oxidase 1 (HAO1). HAO1 encodes glycolate oxidase (GO). By silencing HAO1 and depleting the GO enzyme, Oxlumo inhibits production of oxalate—the metabolite that directly contributes to the pathophysiology of PH1. Oxlumo utilizes Alnylam’s Enhanced Stabilization Chemistry (ESC)-GalNAc-conjugate technology, which enables subcutaneous dosing with increased potency and durability and a wide therapeutic index.

In November of 2020, the FDA approved Oxlumo for the treatment of PH1 to lower UOx levels in pediatric and adult patients. It was also approved by the European Medicines Agency for the treatment of PH1 in all age groups. The Committee for Medicinal Products for Human Use of the EMA delivered a positive opinion recommending variation to the marketing authorization of Oxlumo based on ILLUMINATE-C data from patients with advanced PH1 in September 2022. Oxlumo is also being evaluated in a global phase 2 study as an investigational treatment in patients with recurrent kidney stone disease and elevated UOx levels.

The FDA approval is based on positive six-month results from the ILLUMINATE-C phase 3 study, in which Oxlumo treatment resulted in substantial reductions in POx and demonstrated an encouraging safety and tolerability profile in patients with compromised renal function, including those with kidney failure and undergoing treatment by hemodialysis. Elevated POx is directly related to the pathophysiology of oxalosis and results in systemic deposition of oxalate in extra-renal tissues, potentially leading to bone fractures, cardiomyopathy, impaired erythropoiesis, vision loss, skin ulcers and other serious manifestations.

The supplemental New Drug Application also included results from the open-label extensions of the ILLUMINATE-A and ILLUMINATE-B phase 3 studies of pediatric and adult patients with PH1. The label has correspondingly been updated to highlight the maintenance of sustained reductions in UOx.

“Through the findings of the ILLUMINATE clinical development program, I am thrilled to see the potential benefit of OXLUMO, which remains the first and only FDA-approved PH1 treatment option, now be available for a broad range of people living with the ultra-rare disease, including those advanced PH1 patients undergoing hemodialysis,” said Jorge Capapey, vice president and global rare disease lead at Alnylam Pharmaceuticals.

“The significance of the label expansion of Oxlumo cannot be overstated, as this milestone provides crucial reassurance among a patient population with the highest unmet need, as well as their caregivers and loved ones, that Oxlumo is available in the U.S. for patients living with PH1, including those with advanced disease,” said Kim Hollander, executive director of the Oxalosis and Hyperoxaluria Foundation.

Author: Rare Daily Staff