6.1Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse Reactions in Adult and Pediatric Patients 12 Years of Age and Older with Asthma The safety of TEZSPIRE in asthma was based on the pooled safety population from PATHWAY and NAVIGATOR, which consists of 665 adult and pediatric patients 12 years of age and older with severe asthma who received at least one dose of TEZSPIRE 210 mg subcutaneously once every 4 weeks.
The two placebo-controlled clinical trials were of 52 weeks duration. In addition, a similar safety profile was seen in a trial that enrolled 150 adult patients with severe asthma who required treatment with daily oral corticosteroids [see Clinical Studies (14.1) ] . Adverse reactions that occurred at an incidence greater than or equal to 3% and more common than in the placebo group from the pooled safety population (PATHWAY and NAVIGATOR) are shown in Table 1.
Table 1 Adverse Reactions with TEZSPIRE with Incidence Greater than or Equal to 3% and More Common than Placebo in Patients with Severe Asthma in the Pooled Safety Population (PATHWAY and NAVIGATOR) Adverse Reaction TEZSPIRE N=665 % Placebo N=669 % Pharyngitis Pharyngitis (including Pharyngitis, Pharyngitis bacterial, Pharyngitis streptococcal and Viral pharyngitis) 4 3 Arthralgia 4 3 Back pain 4 3 Specific Adverse Reactions Cardiovascular Events In a randomized, double-blind, long term extension trial, patients 12 years and older with severe asthma from trials NAVIGATOR and the additional trial [see Clinical Studies (14.1) ] received TEZSPIRE 210 mg subcutaneously every 4 weeks or placebo for up to 104 weeks.
In the trial, the incidence rates (IR) per 100 patient-years (PY) for serious cardiac adverse events in patients treated with TEZSPIRE or placebo were 1.08 and 0.21, respectively, with an incidence rate difference (IRD) of 0.88 (95% CI: 0.24, 1.53). The types of serious cardiac adverse events were heterogeneous. In the trial, the IR per 100 PY for adjudicated major adverse cardiovascular events (MACE, defined as cardiovascular deaths, non-fatal myocardial infarctions, and non-fatal strokes) in patients treated with TEZSPIRE or placebo were 0.60 and 0.42, respectively, with an IRD of 0.18 (95% CI: -0.51, 0.75).
Injection Site Reactions In the pooled safety population (PATHWAY and NAVIGATOR), in which TEZSPIRE or placebo was administered using the vial by a healthcare provider, injection site reactions (e.g., injection site erythema, injection site swelling, injection site pain) occurred at a rate of 3.3% in patients treated with TEZSPIRE compared with 2.7% in patients treated with placebo. In an open-label trial of 216 patients with asthma in which TEZSPIRE was administered by healthcare providers and patients or caregivers using either the pre-filled pen or pre-filled syringe, injection site reactions (e.g., injection site erythema, injection site swelling, injection site pain) were observed in 5.7% patients using the pre-filled pen and 0% using the pre-filled syringe.
However, the trial was not designed to compare injection site reactions between patients who received TEZSPIRE by the pre-filled pen versus pre-filled syringe. Adverse Reactions in Adult Patients with Chronic Rhinosinusitis with Nasal Polyps The safety of TEZSPIRE in CRSwNP was based on WAYPOINT, a randomized, double-blind, parallel group, multicenter, placebo-controlled trial of 52 weeks duration, which consisted of 203 adult patients aged 18 years and older on standard of care treatment for CRSwNP who received at least one dose of TEZSPIRE 210 mg subcutaneously once every 4 weeks [see Clinical Studies (14.2) ] .
Adverse reactions that occurred at an incidence greater than or equal to 3% and more common than in the placebo group from the safety population (WAYPOINT) are shown in Table 2. Table 2 Adverse Reactions with TEZSPIRE with Incidence Greater than or Equal to 3% and More Common than Placebo in Patients with CRSwNP (WAYPOINT) Adverse Reaction TEZSPIRE N=203 % Placebo N=205 % Nasopharyngitis 18 10 Upper respiratory tract infection Upper respiratory tract infection (including Upper respiratory tract infection and Viral upper respiratory tract infection) 12 8 Epistaxis 6 3 Pharyngitis Pharyngitis (including Pharyngitis, Pharyngitis bacterial, Pharyngitis streptococcal and Viral pharyngitis) 5 1 Back pain 5 2 Influenza 4 1 Injection site reaction Injection site reaction (e.g., Injection site erythema, Injection site swelling and Injection site pain) 4 2 Arthralgia 3 2
