CTI’s pixantrone gets kicked to the dirt again, but FDA gives some hope
This article was originally published in Scrip
The US FDA again rejected Cell Therapeutics' application for pixantrone as a single-agent treatment for patients with relapsed or refractory aggressive non-Hodgkin's lymphoma – this time denying a dispute appeal request filed in December to conclude that the efficacy of the drug has been demonstrated, the company revealed.
The Seattle-based biotech had received a complete response letter in April 2010 for its application for pixantrone, which followed a rejection a month earlier by the FDA's Oncologic Drugs Advisory Committee, which voted unanimously that the company's data were insufficient for an accelerated approval.
Cell Therapeutics had stopped its Phase III trial of pixantrone with only 140 patients early because of poor accrual, which the firm attributed to preferences for combination regimens in the US and Western Europe or palliative care in late-stage diseases, the widespread adoption of front-line therapy with Rituxan (rituximab) during the course of the study and the limited availability of a patient population meeting the company's eligibility criteria.
The company, however, had failed to consult with the FDA before ending enrollment of the study, whose primary endpoint was complete response (CR) and complete response unconfirmed (CRu) by independent review.
While 20% of patients in the pixantrone arm achieved CR/CRu, versus 5.7% in the comparator arm, five of the pixantrone patients actually had ineligible generally low-grade disease by retrospective central histologic review, the company insisted.
But all is not lost for Cell Therapeutics. The firm said the FDA's Office of New Drugs (OND) concluded that accelerated approval of pixantrone "may not necessarily be out of reach based on a single controlled clinical trial, provided two key matters can be satisfactorily resolved".
The company must submit information about the circumstances surrounding the decision of stopping its single trial early to assure that ongoing results assessment were not dictating the decision to stop. The soundness of the primary endpoint after an additional independent radiologic review must be ascertained.
If those two key matters are addressed satisfactorily, then the firm's study, known as PIX301, could be deemed successful, having achieved its primary and secondary endpoints and a rereview of safety and efficacy would be warranted, Cell Therapeutics said.
"We are gratified and excited that based on a thorough review of our appeal arguments and NDA review that OND provided us the opportunity to re-submit the NDA for re-review and importantly that an additional clinical trial would not necessarily be required for accelerated approval should the two key matters raised be addressed satisfactorily," said CEO Dr James Bianco. "This was the right decision in the interests of patients with relapsed refractory aggressive NHL beyond second line therapy for whom there are no approved or effective drugs."