Sophiris Bio has halted additional doses in an open-label study of topsalysin in prostate cancer, as it investigates the death of a patient who died on the same day he received a second dose of the drug.
The phase 2b trial is the first designed to allow patients to receive a second dose, at six months after initial treatment. Only patients that had not experienced an adverse event linked to topsalysin therapy could be considered, and patients must have previously shown responses to treatment.
Ten more of the trial’s 38 patients received a second dose and will continue to be monitored, with data expected in the fourth quarter of this year—at which point Sophiris will evaluate whether future studies should include additional doses. No additional patients in the trial will receive a second administration while the study continues, the company said in a statement.
“We are extremely saddened by the death of a patient after receiving a second administration of topsalysin,” said Randall Woods, president and CEO of Sophiris. “Understanding the cause of the patient's death is our first priority and essential to determining the potential for re-administration of topsalysin in future clinical trials.”
Still, the company remains hopeful with interim results from single intraprostatic doses: as many as 29% of 35 evaluated patients sustained clinical responses after six months, according to biopsies that showed no detectable tumor or reductions in the tumor to clinically insignificant. No new safety signals were reported in the trial, including no hypersensitivity or other serious systemic reactions, the company said.
“Biopsy results improved from what we saw in the phase 2a proof-of-concept trial and safety and tolerability remains in-line with what we have seen historically,” Woods said, with over 450 patients having received a single administration of topsalysin at various doses. “We believe that the safety and biopsy data from the first administration of topsalysin supports moving forward into potential registration studies.”
In addition, 37% of patients experienced a partial response—though the targeted lesion was still deemed clinically significant—while 34% did not respond to treatment.
Adverse events occurring in more than one patient included dysuria, urinary retention, nocturia, urinary urgency and blockage of the bladder. One case of retention was considered moderate, and resolved after transurethral resection of the prostate and insertion of a catheter.
In May, an independent data monitoring committee recommended the clinical trial continue without changes after reviewing safety data from all 38 patients given a single dose as well the data available on the first seven patients who received a second administration of topsalysin.
Previously known as PRX-302, topsalysin previously met phase 3 endpoints in benign prostatic hyperplasia, or enlarged prostate, improving symptoms in a 12-month study of 479 patients. The success came after a disappointing interim analysis at 12 weeks, with the drug failing to demonstrate significant efficacy.
About 20% of treated BPH patients reported painful urination, though the median duration was less than a day, and no patients withdrew from the trial due to side effects. The drug missed its secondary endpoint of improving urine flow, but improved patient-reported measures of quality of life.