- Alnylam Pharmaceuticals on Tuesday said its experimental drug lumasiran succeeded in a Phase 3 study of patients with an ultra-rare kidney disease, leading the biotech to plan regulatory submissions in the U.S. and Europe in early 2020 for the RNA interference-based medicine.
- The late-stage trial included about 30 patients with primary hyperoxaluria type 1, a genetic disease that causes recurrent kidney stones and damages organs over time, often requiring dialysis and transplants. Alnylam will seek approval based off lumasiran's benefit on urinary excretion levels of a metabolite called oxalate, a biomarker cleared last year by the Food and Drug Administration.
- Alnylam has led the RNA interference field, but one of its closest rivals may soon threaten lumasiran with another RNAi treatment for primary hyperoxaluria. Dicerna Pharmaceuticals has an ongoing pivotal study for DCR-PHXC, testing patients with both Type 1 and Type 2 of the disease.
Alnylam has shown this year how quickly its RNAi platform can advance, winning U.S. clearance for its second product Givlaari (givosiran) and signing a broad R&D deal with Regeneron.
Tuesday's results appear to set the stage for lumasiran's approval but, without detailed data, it's not clear how high they might set the bar for potential competitors following behind it.
Dicerna, a direct rival to Alynlam, also has a drug targeting PH in late-stage testing. Interim Phase 1/2 results showed 14 of 18 patients treated with Dicerna's drug achieved normalization or near-normalization of urinary oxalate levels, a risk factor for developing kidney stones.
Alnylam did not released detailed results Tuesday, saying it would present those at a medical meeting in March 2020. It did say, however, that lumasiran met all primary and secondary goals tested in the trial.
Further out than Dicerna are Allena Pharmaceuticals, which is testing a formulation of the enzyme oxalate decarboxylase in a Phase 2 trial, and Swedish biotech OxThera, currently recruiting patients for a Phase 3 trial of its bacteria-based biologic called Oxabact.
That flurry of clinical development is welcome news for a tiny patient population with few current treatment options. There are no approved drugs for PH1, Alnylam said, although a "small minority" of patients respond to Vitamin B6 treatment. The company estimates between 3,000 and 5,000 people in the U.S. and Europe are affected with the disease.
"When multiple companies solve a problem, problems get solved even better," Alnylam president Barry Greene said Monday in an interview ahead of the announcement, adding that Alnylam's focus will be establishing a competitive profile to lead the market.
With PH1, patients' kidney function can deteriorate to the point of requiring dialysis treatment and dual kidney-liver transplants.
"These patients live with the angst of not knowing when that next kidney stone will come or for how long their kidneys will keep working, and they grapple with the possibility of needing new organs," Kim Hollander, executive director of the Oxalosis and Hyperoxaluria Foundation, said in a statement provided by Alnylam.
Alnylam is conducting two additional Phase 3 studies to expand lumasiran's reach, including one in PH1 patients younger than six years old and another in PH1 patients of all ages with advanced renal disease.
Lumasiran is one of several RNAi drugs that either have reached or are close to reaching market for Alnylam. The Cambridge, Massachusetts-based biotech added Givlaari (givosiran) to its portfolio earlier this year, about a year after the company won the first-ever approval for an RNAi therapeutic with Onpattro (patisiran).
Alnylam has also seen two products it licensed out progress in clinical testing: fitusiran with Sanofi and inclisiran with The Medicines Company. The latter was recently acquired by Novartis for nearly $10 billion.