TROGARZO SIDE EFFECTS

SIDE EFFECTS

The following adverse drug reactions are discussed in other sections of the labeling:

• Immune Reconstitution Inflammatory Syndrome.

Clinical Trial 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.

A total of 292 patients with HIV-1 infection have been exposed to TROGARZO IV infusion.

Trial TMB-301

The primary safety assessment of TROGARZO is based on 24 weeks of data from Trial TMB-301. TMB-301 was a single-arm trial of TROGARZO which enrolled 40 heavily treatment-experienced subjects with multidrug resistant HIV-1 on a failing HIV treatment regimen. Subjects received a single 2,000 mg IV loading dose of TROGARZO followed seven days later by the initiation of an optimized background regimen (OBR) including at least one agent to which the subject’s virus was susceptible. Two weeks after the TROGARZO loading dose, 800 mg of TROGARZO was administered IV. The IV administration of TROGARZO 800 mg was continued every 2 weeks through Week 25.

The most common adverse reactions (all Grades) reported in at least 5% of subjects were diarrhea, dizziness, nausea, and rash. Table 1 shows the frequency of adverse reactions occurring in 5% or more of subjects.

Table 1: Adverse Reactions (All Grades) Reported in ≥ 5% of Subjects Receiving TROGARZO and Optimized Background Regimen for 23 Weeks in Trial TMB-301

Most (90%) of the adverse reactions reported were mild or moderate in severity. Two subjects experienced severe adverse reactions: one subject had a severe rash and one subject developed immune reconstitution inflammatory syndrome manifested as an exacerbation of progressive multifocal leukoencephalopathy.

Laboratory Abnormalities

Table 2 shows the frequency of laboratory abnormalities (≥ Grade 3) in Trial TMB-301.

Table 2: Selected Laboratory Abnormalities (≥ Grade 3) in Trial TMB-301

Immunogenicity

As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing 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 ibalizumab-uiyk in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.

All subjects enrolled in clinical trial TMB-301 and trial TMB-202 (a Phase 2b clinical trial that studied TROGARZO administered intravenously as 2,000 mg every 4 weeks or 800 mg every 2 weeks; the safety and effectiveness of this dosing regimen has not been established), were tested for the presence of anti-ibalizumab antibodies throughout their participation. One sample tested positive with low titer anti-ibalizumab antibodies. No adverse reaction or reduced efficacy was attributed to the positive sample reported in this subject.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of TROGARZO. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

• Immune system disorders: hypersensitivity reactions including infusion-related reactions and anaphylactic reactions have been reported.
• Skin and subcutaneous tissue disorders: pruritus