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 with Intravenous Administration The safety of SAPHNELO was assessed in adult patients with moderate to severe SLE who received SAPHNELO 300 mg by intravenous infusion every 4 weeks (N=459) for 52 weeks, compared to placebo (N=466) in controlled clinical trials (Trials 1, 2 and 3) [see Clinical Studies (14.1) ].
The population studied had a mean age of 41 years (range: 18 to 69), of which 93% were female, 60% White, 13% Black/African American, and 10% Asian. In the controlled-clinical trials, adverse reactions, irrespective of causality, were reported in 87% of patients receiving SAPHNELO and 79% of patients receiving placebo. Adverse reactions that occurred at greater than or equal to 2% incidence are shown in Table 1. Table 1 Adverse Reactions Occurring in ≥2% of Adults with Moderate to Severe SLE Treated with Intravenous SAPHNELO for 52 weeks in Trials 1, 2 and 3 Adverse Reaction SAPHNELO (N=459) % Placebo (N=466) % Upper respiratory tract infection Upper respiratory tract infections (including Upper respiratory tract infections, Nasopharyngitis, Pharyngitis) 34 23 Bronchitis Bronchitis (including Bronchitis, Bronchitis viral, Tracheobronchitis) 11
0.6 All patients received standard therapy. Long-term Safety Patients who completed Trials 2 and 3 (Phase III feeder trials) were eligible to continue on treatment in a randomized, double-blind, placebo-controlled long-term extension (LTE) trial, for an additional 3 years. The long-term safety of SAPHNELO was assessed in 257 patients who received SAPHNELO 300 mg every 4 weeks and 112 patients who received placebo in both a feeder trial and the LTE.
Of these, 177 patients who received SAPHNELO (68.9%) and 52 patients who received placebo (46.4%) completed a total of 4 years on treatment. The overall long-term safety profile of SAPHNELO was consistent with Trials 1, 2 and 3. Specific Adverse Reactions Infections: In the 52‑week controlled-clinical trials, infections were reported in a greater proportion of patients while on treatment with SAPHNELO compared to placebo (69.7% versus 55.4%, respectively).
Herpes Zoster: In the 52‑week controlled-clinical trials, the incidence of herpes zoster in patients while on treatment with SAPHNELO was 6.1% and 1.3% in patients on placebo. Cases with multidermatomal involvement and disseminated presentation have been reported. Of the 28 SAPHNELO-treated patients with herpes zoster, 2 experienced disseminated disease requiring hospitalization compared to none among placebo-treated patients.
Hypersensitivity Reactions Including Anaphylaxis: During the SLE intravenous development program, there was one report of an anaphylactic reaction in a patient who received SAPHNELO 150 mg, and 4 reports of angioedema after 300 mg. In general, the hypersensitivity reactions were predominantly mild or moderate in intensity and did not lead to discontinuation of SAPHNELO. In the 52‑week controlled‑clinical trials, hypersensitivity reactions occurred in 2.8% of patients while on treatment with SAPHNELO and 0.6% of patients on placebo.
Serious hypersensitivity reactions were reported in 0.6% of patients receiving SAPHNELO, including angioedema (n=2). Infusion‑related Reactions: Infusion‑related reactions were mild to moderate in intensity; the most common symptoms were headache, nausea, vomiting, fatigue, and dizziness. In the 52‑week controlled‑clinical trials, the incidence of infusion‑related reactions while on treatment was 9.4% in patients while on treatment with SAPHNELO and 7.1% in patients on placebo.
Malignancies: In 52‑week controlled-clinical trials, malignancies (excluding non‑melanoma skin cancers) were observed in 0.7% and 0.6% of SAPHNELO-treated and placebo-treated patients. Malignant neoplasm (including non‑melanoma skin cancers) was reported in 1.3% of SAPHNELO-treated patients, compared to 0.6% placebo-treated patients. The malignancies that were reported in more than one patient treated with SAPHNELO included breast cancer and squamous cell carcinoma.
Adverse Reactions with Subcutaneous Administration The safety profile of SAPHNELO administered subcutaneously in adult patients with moderate to severe SLE is derived from Trial 5 [see Clinical Studies (14.2) ] . The data reflect SAPHNELO exposure in 185 patients who received SAPHNELO 120 mg by subcutaneous injection once every week, with a median duration of 52 weeks, as compared with comparable exposure to placebo in 182 patients.
