Alnylam nabs speedy review, setting up 3rd possible approval in 3 years
After nearly two decades in the haze of preclinical and clinical development, things seem to be coming into focus for Alnylam Pharmaceuticals.
Two years ago the company landed the first approved drug for RNA interference (RNAi), a Nobel Prize-winning technique discovered in plants and pioneered around the turn of the century. Then last year, they landed another approval. Now, fresh off a massive investment from Blackstone, they’ve received an FDA priority review designation for a third therapy, setting them up to potentially nab three different approvals in three consecutive years.
The review voucher is for an RNAi drug called lumasiran, for use in a rare disease called primary hyperoxaluria type 1, or PH1. The life-threatening disease is caused by an overproduction of oxalate, an end-product of metabolism whose buildup can damage multiple organs, starting with the kidneys. Alnylam’s RNAi drug lowers oxalate levels by silencing the RNA sequences for the enzyme that makes it, glycolate oxidase.
The FDA, which has also granted the drug breakthough therapy status and a pediatric rare disease designation, is scheduled to rule on the drug by December 3. No advisory committee has been scheduled.
For Alnylam, a third approval would be a key step in their march toward profitability. Blackstone invested up-to $2 billion in the company last month, in part in exchange for Alnylam’s share of royalties on a fourth RNAi drug, inclisiran — a potential blockbuster cholesterol injectable that has been submitted to the FDA by Novartis but originally emerged at Alnylam. The move was viewed by analysts as a key step towards making the company profitable. Despite revenue from their first approved drug, Onpattro, they lost nearly a $1 billion last year, as the R&D costs of their growing clinical programs swelled.
If approved, lumasiran will likely look similar to Alnylam’s first two approved drugs: a powerful therapy for a rare condition that comes at a high price. Onpattro, for a fatal condition called hereditary transthyretin-mediated amyloidosis, costs $450,000 per year. The company’s most recently approved drug, Givlaari, for a rare genetic condition called acute hepatic porphyria, sells for $575,000.
In Phase III results announced last December, the drug met both the primary endpoint — the reduction in baseline oxalate over 3 to 6 months — and all six secondary endpoints.
Like the first two Alnylam drugs, lumasiran targets gene expression in the liver. The organ, where the body filters all foreign substances, has been the foremost target for RNA therapeutics, and one of the key long-running questions about the technology is how well Alnylam and others will be able to get their drugs to the rest of the body. Even inclisiran, the cholesterol drug, works by silencing a gene, PCSK9, that’s predominantly expressed in the liver.
An answer, though, may be coming soon. Alnylam’s Covid-19 program will use an inhalant form of RNA, so that it can reach the epithelial cells where Covid-19 takes root. That program is set to enter the clinic in collaboration with Vir Biotechnology by the end of the year.
Lumasiran was included in the Alnylam-Dicerna cross-licensing deal earlier this year, and Dicerna will get royalties if it is approved.