Prevymis Adverse Reactions

Clinical Trials Experience: Adults: Adult CMV-seropositive Recipients [R+] of an Allogeneic HSCT: Prophylaxis Through Week 14 (~100 days) Post-HSCT: The safety of PREVYMIS was evaluated in a Phase 3 randomized, double-blind, placebo-controlled trial (P001) in which 565 subjects were randomized and treated with PREVYMIS (N=373) or placebo (N=192) through Week 14 post-HSCT and were followed for safety through Week 24 post-HSCT.
Cardiac Adverse Events: The cardiac adverse event rate (regardless of investigator-assessed causality) was higher in subjects receiving PREVYMIS (13%) compared to subjects receiving placebo (6%). The most common cardiac adverse events were tachycardia (reported in 4% of PREVYMIS subjects and in 2% of placebo subjects) and atrial fibrillation (reported in 3% of PREVYMIS subjects and in 1% of placebo subjects). Among those subjects who experienced one or more cardiac adverse events, 85% of PREVYMIS and 92% of placebo subjects had events reported as mild or moderate in severity.
The most commonly reported adverse reactions occurring in at least 1% of subjects in the PREVYMIS group through Week 24 post-HSCT and at a frequency greater than placebo were: nausea, diarrhea, and vomiting (see Table 8).

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Hypersensitivity was reported as a non-serious adverse reaction with PREVYMIS in one subject.
Overall, similar proportions of subjects in each group discontinued study medication due to an adverse reaction (4.8% PREVYMIS vs. 3.6% placebo). The most frequently reported adverse reactions that led to discontinuation of PREVYMIS were nausea (1.6%), vomiting (0.8%), and abdominal pain (0.5%).
Laboratory Abnormalities: Overall, the percentage of subjects with potentially clinically significant changes in laboratory values (e.g., hematology, chemistry, renal, and hepatic function) was similar in the PREVYMIS and placebo groups. There were no differences in the incidence of or time to engraftment between the PREVYMIS and placebo groups.
Biomarkers of testicular toxicity were evaluated in male subjects in P001. The changes from baseline in male sex hormones (serum inhibin B, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone) were similar in the PREVYMIS and placebo groups.
Prophylaxis From Week 14 (~100 days) Through Week 28 (~200 days) Post-HSCT: The safety of PREVYMIS was evaluated in a Phase 3 randomized, double-blind, placebo-controlled trial (P040) in which 218 subjects who completed PREVYMIS prophylaxis through ~100 days post-HSCT were randomized to treatment with PREVYMIS (N=144) or placebo (N=74) through Week 28 (~200 days) post-HSCT and were followed for safety through Week 48 post-HSCT.
The adverse reactions observed were consistent with those observed in P001. The most commonly reported adverse reactions occurring in at least 1% of subjects in the PREVYMIS group and at a frequency greater than placebo were: nausea (2.1%) and vomiting (1.4%). A total of 5% of subjects in the PREVYMIS group and 1% of subjects in the placebo group discontinued due to adverse events; none of the adverse events were considered to be related to study medication (PREVYMIS or placebo).
The cardiac adverse event rate (regardless of investigator-assessed causality) was 4% in the PREVYMIS and placebo groups; no cardiac adverse event was reported more than once in either group.
Adult Kidney Transplant Recipients [D+/R-]: The safety of PREVYMIS was evaluated in a Phase 3 randomized, double-blind, active comparator-controlled trial (P002) in which 589 subjects were treated with PREVYMIS (N=292) or valganciclovir (N=297) through Week 28 post-transplant. The most commonly reported adverse reactions occurring in at least 2% of subjects in the PREVYMIS group or valganciclovir group are shown in Table 9. (See Table 9.)

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Study medication was discontinued due to an adverse reaction in 2.7% of subjects in the PREVYMIS group and 8.8% of subjects in the valganciclovir group. The most frequently reported adverse reactions that led to study medication discontinuation were neutropenia (PREVYMIS, 1.4%; valganciclovir, 1.3%) and leukopenia (PREVYMIS, 1.0%; valganciclovir, 5.4%).
The proportion of subjects with leukopenia or neutropenia (adverse events of leukopenia or neutropenia, total white blood cell count <3500 cells/μL, or absolute neutrophil count <1000 cells/μL) through Week 28 post-transplant was lower in the PREVYMIS group compared with the valganciclovir group (PREVYMIS, 26%; valganciclovir, 64%).
Laboratory Abnormalities: Selected laboratory abnormalities reported through Week 28 post-transplant are presented in the table as follows. (See Table 10.)

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