Alnylam Presents New Clinical Results for Givosiran at the 2019 International Congress on Porphyrins and Porphyrias - Seite 3

Updated Phase 1/2 OLE Results
As of the data cut-off date of April 19, 2019, a robust treatment effect was maintained in givosiran-treated patients with continued dosing in the Phase 1/2 OLE study (N=16), with a mean time on treatment of 22.8 months and total time on treatment across the Phase 1 and OLE studies of up to 35 months. Substantial mean reductions in annualized attack rate (AAR) and in annualized hemin use of greater than 90 percent were observed, with evidence for sustained or potentially enhanced clinical activity with continued dosing. Five out of twelve patients (42 percent) who received givosiran during the Phase 1 study and continued with givosiran dosing in the OLE study and two out of four patients (50 percent) who had been in the placebo arm of the Phase 1 study and crossed over to givosiran treatment in the OLE study achieved an AAR of zero for a mean of 18.1 and 24.9 months, respectively.

The overall safety profile of givosiran in the Phase 1/2 OLE as of the data cut-off date remains consistent with that previously reported. Serious adverse events (SAEs) were reported in six patients. Those SAEs not previously reported at earlier data cut-off dates included: one patient with synovitis, assessed as not related to study drug, and one patient with abdominal pain, assessed as unlikely related to study drug. No clinically significant laboratory changes, including liver function tests, were observed with ongoing dosing in the Phase 1/2 OLE study.

The Company and collaborators also presented additional results on a drug-drug interaction study with givosiran, recent analyses from the EXPLORE natural history study, data on patient journey to diagnosis, real-world analysis of illness burden and management, and an overview of AHP symptomology based on peer-reviewed publications and patient narratives.

To view the results presented at ICPP, please visit https://www.alnylam.com/capella.

About Acute Hepatic Porphyria
Acute hepatic porphyria (AHP) refers to a family of rare, genetic diseases characterized by potentially life-threatening attacks and for some patients chronic debilitating symptoms that negatively impact daily functioning and quality of life. AHP is comprised of four subtypes, each resulting from a genetic defect leading to deficiency in one of the enzymes of the heme biosynthesis pathway in the liver: acute intermittent porphyria (AIP), hereditary coproporphyria (HCP), variegate porphyria (VP), and ALAD-deficiency porphyria (ADP). These defects cause the accumulation of neurotoxic heme intermediates aminolevulinic acid (ALA) and porphobilinogen (PBG), with ALA believed to be the primary neurotoxic intermediate responsible for causing both attacks and ongoing symptoms between attacks. Common symptoms of AHP include severe, diffuse abdominal pain, weakness, nausea, and fatigue. The nonspecific nature of AHP signs and symptoms can often lead to misdiagnoses of other more common conditions such as irritable bowel syndrome, appendicitis, fibromyalgia, and endometriosis, and consequently, patients afflicted by AHP often remain without a proper diagnosis for up to 15 years. In addition, long-term complications of AHP and its treatment can include chronic neuropathic pain, hypertension, chronic kidney disease and liver disease, including iron overload, fibrosis, cirrhosis and hepatocellular carcinoma. Currently, there are no treatments approved to prevent debilitating attacks or to treat the chronic manifestations of the disease.