Alnylam Pharmaceuticals (Nasdaq: ALNY) is presently in the midst of a Phase III study of givosiran, reporting that the drug has been successful in a clinical trial. The company hopes to use their trial data in getting givosiran approved by the U.S. Food and Drug Administration (FDA). Alnylam named their company after “Alnilam”, which is the name of the brightest star in Orion’s belt. The company describes themselves as “leading the translation of RNA interference (RNAi) into a whole new class of innovative medicines with the potential to transform the lives of patients who have limited or inadequate treatment options. Based on Nobel Prize-winning science, RNAi therapeutics represent a powerful, clinically validated approach for the treatment of a wide range of debilitating diseases with high unmet medical need. Alnylam was founded in 2002 on a bold vision to turn scientific possibility into reality, which is now marked by its robust discovery platform and deep pipeline of investigational medicines, including 4 programs in late-stage clinical development.”
The Phase III clinical trial of givosiran has been labeled “ENVISION”, and hopes to evaluate the effect of givosiran on the rate of porphyria attacks, in subcutaneous form versus placebo, in patients with acute hepatic porphyrias (AHPs). «Givosiran (ALN-AS1) is an investigational, subcutaneously-administered RNA interference (RNAi) therapeutic targeting aminolevulinic acid synthase 1 (ALAS1) in development for the treatment of AHPs,” according to Alnylam’s ENVISION infographic. The study was originally initiated in November 2017 and is now in its Phase III Interim Analysis. The specific trial data is not available to the public as of yet due to the ongoing nature of the study.
AHPs is a group of genetic metabolic disorders that cause multiple life-threatening symptoms as well as seizures, nervous system attacks, brain fog, and chronic pain. Alnylam General Manager Akin Akinc described the disease as “incompatible with life” to the Boston Business Journaldue to the debilitating suffering AHPs causes patients in its most serious form. The Phase III study of givosiran revealed positive data that almost half of the 94 trial participants eclipsed the commonly used drug trial probability standard. «We have an incredible amount of confidence that the drug does what it’s meant to do,» Akinc added. «Clearly, this tells us that we’re on the right track.» The four types of AHPs: acute intermittent porphyria (AIP), hereditary coproporphyria (HCP), variegate porphyria (VP), and δ-aminolevulinic acid dehydratase porphyria (ADP) are extremely rare, combinedly affecting approximately 5 in every 100,000 people. A positive mid-trial result could eventually indicate life-changing effects for afflicted patients in the future, especially considering that there are currently no approved treatments for debilitating attack or chronic symptom preventions. Alnylam has received FDA approval for revolutionary treatments in the past, such as the first and only RNA interference (RNAi)therapeutic, Onpattro (patisiran), which treats adults for the polyneuropathy of hereditary transthyretin-mediated (hAATR) amyloidosis.
The Phase III randomized trial is “enrolling approximately 75 patients, age 12 or older, with AHPs at clinical centers in more than 20 countries worldwide.” Each patient is being completely randomly assigned either a placebo or the givosiran in a 2.5 mg/kg dose, administered once a month over a treatment period of six totalmonthsh. “A planned interim analysis, agreed upon with the Food and Drug Administration (FDA), will evaluate reduction in biomarker levels – aminolevulinic acid (ALA) – that may reasonably predict clinical benefit. Reduction in ALA will be evaluated in 30 patients after three months of dosing. All patients completing the six-month treatment period, with either givosiran or placebo, may be eligible to continue on an open-label extension (OLE) study in which they will receive treatment with givosiran for up to 30 months.” At the end of the trial, Alnylam will release data outlining the rate of annualized porphyria attacks over the study period of six months. The completed data will also include givosiran’s quality of life affectations on AHP afflicted patients, including the reduction of chronic symptoms such as fatigue, nausea, and pain.
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