Credit: NIH
The US Food and Drug Administration and the European Commission have granted volasertib orphan designation for the treatment of acute myeloid leukemia (AML).
Volasertib, an investigational inhibitor of polo-like kinase 1 (Plk1), works by arresting the cell cycle and inducing apoptosis.
The drug is under evaluation as a potential treatment for patients aged 65 or older with previously untreated AML who are ineligible for intensive remission induction therapy.
In both the US and the European Union, orphan designation is awarded for drugs intended to treat rare conditions for which no authorized treatment exists. The designation gives the company developing volasertib, Boehringer Ingelheim, regulatory support and incentives to help the development and authorization process.
Volasertib has already been tested in a phase 1/2 trial of patients with newly diagnosed AML who were considered ineligible for intensive remission induction therapy. The results were presented at the 2012 ASH Annual Meeting as abstract 411.
In this study, volasertib in combination with low-dose cytarabine (LDAC) elicited higher rates of objective response and an improvement in event-free survival, when compared to LDAC alone.
Eighty-seven AML patients were assigned to receive volasertib + LDAC (n=42) or LDAC alone (n=45). Patient characteristics were similar between the 2 groups.
The objective response rate was 31% among patients who received volasertib + LDAC and 11.1% in those who received LDAC alone. The complete response rates were 16.7% and 6.7%, respectively.
The median event-free survival was 169 days for patients who received volasertib + LDAC and 69 days for patients who received LDAC alone.
Grade 3 or higher adverse events were more common in the volasertib + LDAC arm than the LDAC-alone arm—95.2% vs 68.9%.
The most frequent adverse events of any grade occurring in the volasertib + LDAC arm were febrile neutropenia (50%), constipation (45.2%), nausea (40.5%), and anemia (40.5%).
In the LDAC-alone arm, the most common adverse events were nausea (33.3%), anemia (28.9%), pyrexia (28.9%), constipation (26.7%), asthenia (26.7%), and diarrhea (26.7%).
Based on these results, researchers initiated a phase 3 study, called POLO-AML-2, comparing volasertib plus LDAC to LDAC plus placebo in older AML patients.
