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XBiotech Announces Top-Line Results for 514G3 Antibody Therapy in Serious Staphylococcus aureus Infections
The study involved use of the Company’s proprietary 514G3 antibody derived from a natural human immune response against a key virulence determinant of S. aureus that is present on all strains of the bacteria, including MRSA. In the study, hospitalized adult patients with confirmed blood infections were randomized 3:1 (514G3 vs placebo) during a dose escalation phase to establish a Phase II dose. The Phase II portion was randomized 2:1 at the established Phase II dose of 40 mg/kg. A total of 52 patients were enrolled: 36 received 514G3 and 16 received placebo. Thirty of the 36 patients that were given 514G3 received the established Phase II dose (40 mg/kg).
The study was the first in-human use for 514G3 using exploratory endpoints in a small population. Thus, the study was not powered to demonstrate statistically significant outcomes. Nevertheless, several key topline results from the clinical study were observed.
No drug-related adverse events were observed at any of the dose escalation levels and the 40 mg/kg Phase II dose was established without any dose-limiting toxicities (DLTs). The duration of hospitalization and incidence of serious adverse events (SAEs) were key clinical endpoints which the Company is exploring as a basis for evaluating effectiveness of the therapy. SAEs thus served as both a measure of safety and of efficacy for the 514G3 therapy. Blinded analyses for SAEs were independently performed by the study chair, treating investigators, and an independent expert. A total of 28 SAEs in 15 patients were reported during the study period including 4 deaths. There was a 49% relative risk reduction for the overall incidence of SAEs in subjects receiving 514G3 compared to those receiving placebo [(8 of 36 (22%) vs 7 of 16 (44%), respectively, (p=0.11)]. There was an even greater risk reduction in the incidence of S. aureus related SAEs in those that received 514G3 treatment compared to placebo, with a 56% relative risk reduction in the 514G3 group [4 of 36 (11%) vs 4 of 16 (25%), respectively, (p=0.23)]. The trend seen with overall and disease specific reduction in SAEs was a key outcome in the study and an important potential indication of 514G3 efficacy.
Another clinically important secondary endpoint was the average length of hospitalization for patients from the time they entered study. The duration of hospitalization was reduced by about 33% in the 514G3 treatment arm compared to the placebo arm [8.6±7 days vs 12.7±9 days, respectively (p=0.092)] [median 7.5 (IQR 4–9) vs median 12 (IQR 5.5–19), respectively]. Given the complexity of the co-morbidities in the population and the small study size, observing reduced hospital stay in the 514G3 group suggests a considerable impact on resolution of disease, less patient morbidity and a potential reduction in healthcare expenditures for subjects receiving the antibody therapy.
Other findings in this study were that randomization failed in the small sample size to provide well matched populations with respect to co-morbidities between treatment and placebo arms. Subjects who were randomized in the 514G3 treatment arm tended to be sicker and have greater numbers of serious co-morbid conditions and greater risk of complications. Seventy-eight percent of the 514G3 treated patients were admitted to the hospital via the
S. aureus bacteremia is a very serious medical problem that is associated with a 30-day mortality rate of 20%-30% despite treatment with antibiotics. S. aureus is becoming increasingly resistant to antibiotics and new treatment modalities are urgently needed. The CDC has graded methicillin-resistant S. aureus (MRSA) as a serious threat to public health and estimates that over 80,000 serious MRSA infections occur in the U.S. each year resulting in over 11,000 deaths.
About True Human™ Therapeutic Antibodies
XBiotech’s True Human™ antibodies are derived without modification from individuals who possess natural immunity to certain diseases. With discovery and clinical programs across multiple disease areas, XBiotech’s True Human antibodies have the potential to harness the body’s natural immunity to fight disease with increased safety, efficacy and tolerability.
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Ashley Oteroaotero@xbiotech.com 512-386-2930