A review of clinical records and information from the autopsy point to a sudden cardiac event caused by an arrhythmia as the most likely cause of death; the patient had multiple risk factors for the condition. Bloodwork also excluded an acute hypersensitivity to the drug.
The patient died after a second administration of topsalysin in a Phase 2b trial (NCT03081481). As a precaution, no additional patients received a second administration.
Regulatory agencies in the United States and the United Kingdom, where the study is being conducted, have been notified of the findings and are expected to support the study’s continuation.
“Topsalysin continues to appear to be well-tolerated with no new safety signals reported,” Randall E. Woods, president and CEO of Sophiris, said in a press release. “We look forward to reporting the complete efficacy and safety data from the Phase 2b study by the end of the year, which will include the biopsy and safety data from the 10 patients who received a second administration of topsalysin.”
Topsalysin is an engineered protein that forms small pores in cells, causing their contents to leak and leading to their death. To prevent damage to healthy cells, the protein is made to become active only in the presence of PSA, which is increased in prostate cancer cells.
The Phase 2 trial is testing topsalysin, delivered directly into the prostate, as a treatment for men with low- to intermediate-risk prostate cancer.
Results released in June 2018 showed that 10 of the 38 patients (29%) who received a single administration of topsalysin responded to the treatment. A response was defined as a complete tumor clearance — seen in six patients — or a reduction so striking that the lesion became clinically insignificant.
Biopsy results also revealed that 13 patients (37%) experienced a partial response — the lesion is smaller but still considered clinically significant. Twelve patients (34%) did not respond to treatment.
Patients without clinically significant adverse events and who responded to the treatment were eligible for a second administration of topsalysin. This re-administration was to have evaluated whether additional benefits were observed.
“We are very encouraged with the results from the single administration of topsalysin in our Phase 2b study,” Woods said. “We continue to plan and move forward with a potential Phase 3 study design based on the response rates and safety profile we have observed to date.”
In May 2018, an independent data monitoring committee (IDMC) reviewed the safety data from all 38 patients treated with a single dose of topsalysin, as well the data available on the first seven patients who received a second administration.
The IDMC considered that there were no safety concerns related to the treatment or the procedure, and unanimously recommended the trial’s continuation without changes to the protocol.