- Alnylam Pharmaceuticals plans to launch a Phase 3 study of its experimental therapeutic givosiran later this year, potentially adding a fourth drug to its late-stage pipeline of treatments designed to "silence" messenger RNA and thereby block disease-causing proteins from being made.
- Interim data from a placebo-controlled Phase 1 study suggested treatment with givosiran could help patients with acute hepatic porphyrias, a class of ultra-rare metabolic diseases caused by mutations in the heme synthesis pathway.
- Givosiran recently received the European Medicines Agency's PRIME designation, a program that boosts collaboration between drugmakers and the regulator to speed drug development. The Food and Drug Administration previously tagged givosiran with its Breakthrough Therapy designation, which bestows similar benefits.
Alnylam has pegged 2017 as a key inflection point in its maturation as a company, aiming to file its first applications for regulatory approvals on its lead candidate patisiran if all goes well in a Phase 3 study slated to read out later this year.
The biotech, a specialist in RNA interference (RNAi) therapeutics, hopes to make the leap towards becoming a multi-product commercial-stage company by the end of 2020. Givosiran would round out a Phase 3 pipeline which includes patisiran as well as fitusiran in hemophilia and inclisiran in hypercholesterolemia.
Progress towards that 2020 goal hasn't been completely smooth, however. Shares in the biotech shed nearly 50% of their value in October after Alynlamy abandoned further development of its then-lead candidate revusiran.
Givosiran, the earliest stage candidate of the four therapies next in line, targets a liver-expressed enzyme known as aminolevulinic acid synthase 1 (ALAS1). Alnylam believes silencing ALAS1 should reduce the accumulation of toxic heme intermediates and thereby prevent or lower porphryia attacks and symptoms.
In Part C of the Phase 1 study, givosiran successfully inhibited ALAS1, lowering the prevalence of the heme intermediates and reducing the annualized number of porphyria attacks by an average of 63% in the nine treated patients.
Three patients had four serious adverse events, none of which were judged to be related to the study drug. One patient died from hemorrhagic pancreatitis, which the investigator deemed unlikely to be associated with treatment.
Alynlam is also conducting a natural history study of acute hepatic porphryia. Updated 12-month data from that study showed the annualized attack rate was approximately five attacks per person with an average duration per attack of seven days. Porphryia attacks generally require treatment in a hospital or urgent care site.
Analysis of costs, which Alnylam bills as the first of its kind in the U.S., put estimate annual expenditure per patient between $400,000 to $650,000 — a clue to how the company is considering potential value of a therapeutic remedy. Those figures only include direct costs and not indirect costs such as lost productivity, Alnylam said.
Moving forward, Alnylam will continue Part C of the study and dosing in an open-label extension study, laying the groundwork for a potential Phase 3 initiation.