Dive Brief:
- Alnylam on Thursday said it plans to start late-stage testing of its rare disease drug candidate lumasiran by the middle of this year, having secured agreement from the Food and Drug Administration to use a biomarker for primary analysis of the RNAi drug's clinical effect in treating primary hyperoxaluria type 1.
- As a result, Alnylam expects a topline readout from the study could come by 2019, with a submission for U.S. approval possible in early 2020 — a timeline that highlights the biotech's desire to further broaden its late-stage clinical pipeline.
- The FDA endorsed Alnylam's proposal to measure reduction in urinary oxalate reduction at six months as the primary endpoint of the Phase 3 study, the company said. Urinary oxalate is a biomarker correlated with disease progression.
Dive Insight:
Alnylam has been working on RNA interference-based therapeutics for the better part of two decades, pouring over a billion dollars into R&D. Its persistence appears to now be paying off.
Last November, the biotech's lead drug patisiran swept its primary and secondary endpoints in a Phase 3 study of patients with hereditary ATTR (hATTR) amyloidosis, and approval in the U.S. looks likely by late summer.
Givosiran, a candidate for acute hepatic porphyrias, is also in late-stage testing, and Alnylam holds rights to royalty payments on two other drugs in Phase 3 development by Sanofi and The Medicines Company.
Lumasiran's move into Phase 3, pushed forward after Sanofi dropped its option for the development and commercialization in March 2018, would give Alnylam a third, wholly-owned asset in registration or late-stage testing.
Early results from an ongoing Phase 1/2 study showed all four patients dosed with lumasiran reached a normal or near normal level of urinary oxalate. Urinary oxalate excretion also fell below levels linked with a reduced progression to end-stage renal disease.
"Given the preliminary results reported to date, we believe that investigational lumasiran has the potential to prevent excessive oxalate production implicated in the pathophysiology and morbidity associated with PH1, an ultra-rare, life-threatening disease," said Pritesh Gandhi, head of Alnylam's Lumasiran program, in a May 3 statement.
Primary hyperoxaluria type 1 (PH1) leads to the accumulation of calcium oxalate crystals in the kidney and urinary tract, with around half of patients developing kidney failure by the age of 15. Eight in ten experience end-stage renal disease by the age of 30. People with PH1 may also have crystals forming in bones, eyes, skin and heart. Treatment options include dialysis or liver and kidney transplantation, and there are no approved drugs for PH1.