The ink is barely dry on its second FDA approval, but Alnylam is already gearing up for the next one. Its kidney disease drug beat placebo at helping patients clear a substance called oxalate from their kidneys, hitting its goal in a phase 3 study. The company plans to file the drug for approval in the U.S. and Europe early next year.
Alnylam developed lumasiran to treat the rare, genetic disorder primary hyperoxaluria type 1 (PH1). Healthy kidneys filter oxalate out of the blood so the body can get rid of it through urine. But the substance builds up in the kidneys of people with PH1, where it binds to calcium to form the main component of kidney stones. Left untreated, the disorder can lead to kidney failure. Some patients end up needing kidney or liver transplants.
With an enrollment goal of 30 patients, Alnylam reckons the phase 3 Illuminate-A study is the largest so far to test a treatment for PH1. Patients received lumasiran or placebo once a month for the first three months before switching maintenance doses every three months. Lumasiran hit the mark at improving 24-hour urinary oxalate excretion from baseline, as measured over months three to six, Alnylam said in a statement.
The drug also met all six secondary endpoints, including the proportion of patients who achieved normal or near-normal levels of oxalate levels in their urine. It also posted an “encouraging” safety and tolerability profile.
“The results from ILLUMINATE-A demonstrate that lumasiran can significantly reduce the hepatic production of oxalate, which we believe can thereby address the underlying pathophysiology of PH1,” said Akshay Vaishnaw, M.D., Ph.D., Alnylam's R&D chief, in the statement. “Further, we are encouraged by the safety and tolerability profile of lumasiran and believe this investigational medicine has the potential to have a meaningful clinical impact on patients living with PH1.”
Assuming all goes well with lumasiran and its PCSK9 drug inclisiran, Alnylam could bring its total marketed products number to four by the end of 2020. Its partner, The Medicines Company, wrapped up the phase 3 program for the cholesterol med this fall with plans to file for U.S. approval by the end of the year, just in time for its $9.7 billion buyout by Novartis.
Following behind is the Sanofi-partnered hemophilia program, fitusiran. Sanofi once had the option to pick up the rights to lumasiran outside of the U.S. and western Europe, but turned it down in March 2018 shortly after the duo retooled their partnership to divide their rights by asset rather than by geography. In that overhaul, Alnylam regained global rights to patisiran, now sold as Onpattro, and Sanofi picked up global rights to fitusiran.