TABLE 4

ADRs and toxicity of the FDA-approved ASO and siRNA drugs for the treatment of the SDLO diseases

Group	ASO or siRNA drug	Black Box Warning	Warnings and Precautions	Common ADRs >5%	Less Common ADRs <5%	Immuno-genicity
No toxicity	Lumasiran	No	No	Injection site reactions, abdominal pain		No indication
No toxicity	Inclisiran	No	No	Injection site reactions, arthralgia	Urinary tract infection, diarrhea, bronchitis, pain in extremity, dyspnea	No evidence
Mild toxicity	Vutrisiran	No	Reduced serum vitamin A	Arthralgia, dyspnea, vitamin A decreased	Injection site reactions	Inconclusive
	Patisiran	No	Infusion-related reactions, reduced vitamin A levels	Upper respiratory tract infections, infusion-related reaction, dyspepsia, dyspnea, muscle spasms, arthralgia, erythema, bronchitis, vertigo	Ocular adverse reactions, blurred vision, vitreous floaters, extravasation	Inconclusive
	Givosiran	No	Anaphylaxis, Hepatic toxicity Renal toxicity Injection site reactions	Nausea, injection site reactions, rash, serum creatinine increase, transaminase elevations, fatigue	Anaphylated reaction, hypersensitivity	No indication
Severe toxicity	Inotersen	Thrombo-cytopenia, Glomerulo-nephritis, REMS program	Thrombocytopenia, Glomerulonephritis and renal toxicity Stroke and cervicocephalic arterial dissection Inflammatory and immune effects Liver effects Hypersensitivity reactions, Uninterpretable platelet counts, Reduced serum vitamin A	Injection site reactions, nausea, headache, fatigue, thrombocytopenia, fever, peripheral edema, chills, anemia, vomiting, myalgia, decreased renal function, arrhythmia, arthralgia, pre-syncope, decreased appetite, paresthesia, dyspnea, elevated liver function, orthostasis, influenza like illness, contusion,	Bacterial infection, eosinophilia, dry mouth	Positive for anti-inotersen antibodies
Severe toxicity	Mipomer-sen	Hepato-toxicity REMS program	Hepatotoxicity Elevation of transaminases Hepatic steatosis Injection site reactions Flu-like symptoms	Injection site reactions, fatigue, nausea, influenza like illness, headache, ALT and AST increased, pyrexia, hypertension, pain in extremity, hepatic steatosis, chills, edema peripheral, and liver function abnormal	Angina pectoris, musculoskeletal pain, vomiting, palpitations, abdominal pain, and insomnia	Positive for antimipomersen antibodies.