Positive Interim Results from Ongoing Phase 1 Study with ALN-AS1, in Development for the Treatment of Acute Hepatic Porphyrias

We presented interim results from our ongoing Phase 1 clinical trial with ALN-AS1, an investigational RNAi therapeutic targeting aminolevulinic acid synthase 1 (ALAS1) for the treatment of acute hepatic porphyrias (AHP), at the 2016 Society for the Study of Inborn Errors of Metabolism (SSIEM) Annual Symposium, held from September 6 – 9, 2016 in Rome, Italy.

New data were from Parts A and B of the Phase 1 study, conducted in asymptomatic “high excreter” (ASHE) subjects. These subjects have a mutation in the porphobilinogen deaminase (PBGD) gene as found in acute intermittent porphyria (AIP), and have elevated levels of aminolevulinic acid (ALA) and porphobilinogen (PBG), the toxic heme synthesis intermediates that mediate porphyria attacks.

Results as of the data transfer date of June 28, 2016 showed that ALN-AS1 administration resulted in rapid, dose-dependent, and durable silencing of liver ALAS1 mRNA in both Part A (N=20) and Part B (N=8) of the trial.  In addition, data showed rapid and dose-dependent lowering of ALA and PBG of up to 95%.  Reductions in ALA and PBG were highly durable, with effects lasting for over ten months after a single dose.

ALN-AS1 continued to be generally well tolerated in ASHE subjects as of the data transfer date.  There were three serious adverse events (SAEs) that were all deemed to be unlikely related to study drug.  With the exception of one AE that was severe and unrelated to study drug, all other AEs were mild or moderate in severity, most commonly including abdominal pain, diarrhea, hypoesthesia, nasopharyngitis, pruritis, and rash.  There were no clinically significant changes in vital signs, electrocardiograms, clinical laboratory parameters, or physical examination.

We look forward to the continued advancement of ALN-AS1, which we believe has the potential to be a transformative therapy for patients with acute hepatic porphyrias suffering from recurrent attacks, a group of ultra-rare orphan diseases with enormous unmet medical need.