Alnylam Pharmaceuticals has launched the Phase III ENVISION clinical trial to investigate givosiran in patients with acute hepatic porphyrias (AHPs), a rare autosomal dominant condition.
Formulated for subcutaneous administration, givosiran is an RNAi therapeutic being developed to target aminolevulinic acid synthase 1 (ALAS1), the increase of this is known to cause the disease.
The global, randomised, double-blind, placebo-controlled, multi-centre Phase III trial will assess the safety and efficacy of monthly 2.5mg/kg dose of givosiran in around 75 subjects over six months across more than 20 countries.
ENVISION’s primary endpoint is the annualised rate of porphyria attacks requiring hospitalisation, urgent healthcare visit or at-home hemin administration, while the key secondary and exploratory endpoints will monitor disease symptoms such as pain, nausea and fatigue, along with quality of life.
Patients completing the six-month treatment period will be eligible to participate in an open-label extension (OLE) study involving givosiran treatment for up to 30 months.
Givosiran programme general manager Jeff Miller said: “Based on our Phase I and Phase II open-label extension study results, we believe that givosiran could meaningfully reduce the frequency of attacks requiring hospitalisations and the need for hemin, with an encouraging tolerability profile.”
The firm has also partnered with the Medicines Company to conduct a Phase III clinical programme of inclisiran, which is a GalNAc-conjugated RNAi therapeutic designed to target PCSK9 protein regulator.
Under the programme, the Phase III ORION-11 trial commenced inclisiran dosing for the treatment of patients suffering from atherosclerotic cardiovascular disease (ASCVD), or ASCVD-risk equivalents and increased LDL-cholesterol (LDL-C) even after maximum tolerated doses of LDL-C lowering regimens.
The subcutaneous 300mg dose of inclisiran will be evaluated in 1,500 subjects over 18 months at 100 clinical centres across seven countries in Europe and South Africa.