Alnylam starts phase 1/2 trial for ALN-GO1 to treat Primary Hyperoxaluria Type 1

The Phase 1/2 trial will be conducted initially in normal healthy volunteers, and, then, in patients with PH1. Initiation of this trial is based on encouraging pre-clinical data presented last year.

The Company has guided that it expects to report initial clinical activity data from this trial in late 2016 and also announced that it has been granted Orphan Drug Designation for ALN-GO1 from the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA).

PH1 is an ultra-rare orphan disease affecting approximately 5,000 people worldwide. This devastating disease – which is often diagnosed in early childhood – is an inborn error of metabolism resulting in excessive oxalate production, kidney failure and further organ damage for some patients in infancy and most patients by their mid-twenties.

There are no approved medical therapies for PH1, leaving frequent renal dialysis as palliative care and combined liver/kidney transplant as the only potentially curative option.

Left untreated, excessive oxalate production can lead to severe illness and death. ALN-GO1 targets the gene for glycolate oxidase (GO), an enzyme upstream of the defect in PH1 patients, and is designed to starve the pathway of oxalate production and prevent its associated pathology.

"We believe ALN-GO1 has the potential to be a transformative therapy for patients with PH1, a serious disease in young children, where combined liver/kidney transplantation is the only potentially curative option," said Akshay Vaishnaw, M.D., Ph.D., Executive Vice President of R&D and Chief Medical Officer of Alnylam.

"ALN-GO1 is the eighth clinical program in our rapidly growing pipeline of investigational RNAi therapeutics. Our pre-clinical results suggest that ALN-GO1 has the potential to achieve disease modifying effects with durability supporting a once-monthly and potentially once-quarterly subcutaneous dose regimen. We look forward to advancing this novel therapeutic candidate through the clinic and expect to share initial Phase 1/2 clinical activity data in late 2016."

The Phase 1/2 trial of ALN-GO1 is a randomized, single-blind, placebo-controlled study being conducted in two parts. Part A is a single-dose study designed to enroll up to a total of 40 normal healthy volunteers (NHV). Part B will be a multi-dose study designed to enroll up to a total of 20 patients with PH1.

The primary objective of the study is to evaluate safety and tolerability of single and multiple subcutaneous doses of ALN-GO1. Secondary objectives include evaluation of pharmacokinetics and clinical activity for ALN-GO1 as measured by its effects on serum glycolate and urinary oxalate levels in NHV and PH1 patients, respectively.

ALN-GO1 Pre-clinical Data

Pre-clinical data were presented at the 48th European Society of Paediatric Nephrology (ESPN) Annual meeting, held September 3 – 5, 2015 in Brussels, showing that:

ALN-GO1 demonstrated potent and durable silencing (up to 99 percent) of HAO1 mRNA (the gene for glycolate oxidase) across species and robust lowering of urinary oxalate (up to 98 percent) in animal models of PH1.
In addition, pre-clinical durability data support a once-monthly, and potentially once-quarterly, subcutaneous dose regimen with ALN-GO1.