Shares in Iterum Therapeutics plunged as much as 46% on Wednesday after the company reported that a Phase III study of the investigational penem antibiotic sulopenem in patients with complicated intra-abdominal infections (cIAI) failed to meet its primary endpoint.
The SURE 3 trial randomised patients with cIAIs to initially receive either sulopenem or ertapenem. Patients in the first group received intravenous sulopenem once daily for a minimum of five days followed by oral sulopenem/probenecid twice daily to complete seven to 10 total days of treatment. Meanwhile, those in the second group were administered intravenous ertapenem once daily for a minimum of five days followed by oral ciprofloxacin twice daily along with oral metronidazole four times a day, or for those with ciprofloxacin-resistant organism at baseline, twice-daily amoxicillin-clavulanate was given instead. The study's main goal was based on clinical response at day 28 in patients with a positive intra-abdominal culture at baseline.
Top-line results at the test of cure showed that clinical response on day 28 in the micro-modified intention-to-treat (microMITT) population was 85.5% in the sulopenem group compared to 90.2% for the ertapenem group, representing a difference in outcomes of 4.7% with a 95% confidence interval on that difference of -10.3% to 1.0%. Iterum noted that non-inferiority required that the lower limit of the difference in the outcome rates be greater than -10% in order to meet the FDA's guidelines.
"While the difference in the primary outcome is one patient shy of the target of -10%, imputing an outcome for the patients with missing data and the secondary supporting analyses, both at the end of treatment as well as the test of cure, provide support for the potential of sulopenem in the treatment of multi-drug resistant infections," remarked chief scientific officer Michael Dunne.
Iterum said an analysis designed to address any imbalances in patients with indeterminate outcomes at the test of cure in the microMITT population, showed that the difference in outcomes was 4.7% with a 95% confidence interval of -9.9% to 0.5%. Meanwhile, end-of-treatment data showed that clinical response in the microMITT population was 83.5% for sulopenem versus 85.3% for ertapenem-treated patients, a difference of 1.8% with a 95% confidence interval between -8.1% and 4.5%.
In the safety population of 668 patients, Iterum said treatment-related adverse events were observed in 6% and 5.1% of patients in the sulopenem and ertapenem groups, respectively, with the most common side effects being diarrhoea, which occurred at respective rates of 4.5% and 2.4%. Discontinuations were uncommon on both regimens, the company added.
CEO Corey Fishman said that "if we obtain positive results in the first quarter of 2020 from our Phase III complicated and uncomplicated urinary tract trials, we believe that the overall safety and efficacy results from this cIAI trial would be supportive in an FDA filing for oral and intravenous sulopenem and that sulopenem's market potential remains robust."
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