1 Adverse Reaction Overview The most frequently occurring adverse reactions reported in ONPATTRO-treated patients (≥ 10% of patients and occurring ≥ 3 percentage points more frequently than in placebo-treated patients) were peripheral edema and infusion-related reactions (see 7 WARNINGS AND PRECAUTIONS).
7%). 2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials, therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.
Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use. 1 years. Of these 224 patients, 186 patients received ≥ 1 year of treatment, 137 patients received ≥ 2 years of treatment, and 52 patients received ≥ 3 years of treatment.
7 months. 2 Dosage and Dosage Adjustment). , having baseline left ventricular (LV) wall thickness ≥ 13 mm, with no history of hypertension or aortic valve disease. Adverse reactions for ONPATTRO are defined as those adverse events occurring at a ≥ 3 percentage point higher frequency in patients treated with ONPATTRO, compared with placebo, and other potentially relevant adverse events based on other studies with ONPATTRO.
0), sorted under the respective System Organ Class (SOCs) (Table 2). Page 13 of 32 Table 2 – Adverse Reactions That Occurred at a ≥ 3 Percentage Point Higher Frequency with ONPATTRO Compared to Placebo in the APOLLO Trial ONPATTRO N=148 (%) Placebo N=77 (%) General disorders and administration site conditions Peripheral edema 30 22 Immune system disorders Infusion-related reaction* 19 9 Gastrointestinal disorders Dyspepsia 8 4 Musculoskeletal and connective tissue disorders Muscle spasms Arthralgia 8 7 1 0 Respiratory, thoracic and mediastinal disorders Dyspnea 7 0 Skin and subcutaneous tissue disorders Erythema 7 3 Infections and infestations Bronchitis Rhinitis Sinusitis 6 4 4 3 0 0 Ear and labyrinth disorders Vertigo 5 1 *Infusion-related reaction symptoms include but are not limited to: arthralgia or pain (including back, neck, or musculoskeletal pain), flushing (including erythema of face or skin warm), nausea, abdominal pain, dyspnea or cough, chest discomfort or chest pain, headache, pruritus, rash, chills, dizziness, fatigue, increased heart rate or palpitations, hypotension (which may include syncope), hypertension, facial edema.
3 Pharmacokinetics). 3 Less Common Clinical Trial Adverse Reactions General disorders and administration site conditions: extravasation, including phlebitis or thrombophlebitis, infusion or injection site swelling, dermatitis, cellulitis, erythema or injection site redness, burning sensation, or injection site pain.
4 Abnormal Laboratory Findings: Hematologic, Clinical Chemistry and Other Quantitative Data Immunogenicity Anti-drug antibodies to ONPATTRO were evaluated by measuring antibodies specific to PEG2000-C-DMG, a lipid component exposed on the surface of ONPATTRO.
6%) patients with hATTR amyloidosis developed anti-drug antibodies, as measured during treatment with ONPATTRO. One additional patient had pre-existing anti-drug antibodies. Anti-drug antibody titers were low and transient with no evidence of an effect on clinical efficacy, the safety profile, or the pharmacokinetic or pharmacodynamic profiles of ONPATTRO.
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. In addition, the observed incidence of antibody positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications and underlying disease.
For these reasons, comparison of the incidence of antibodies to ONPATTRO with the incidence of antibodies to other products may be misleading. Vitamin A Levels Serum TTR is a carrier of retinol binding protein, which facilitates transport of vitamin A in the blood.
Treatment with ONPATTRO reduces serum TTR levels, which results in reduced levels of retinol binding protein and vitamin A in the serum (see 7 WARNINGS AND PRECAUTIONS).