Image by Lance Liotta
AML cells
The European Medicines Agency’s Committee for Orphan Medicinal Products (COMP) has recommended that PCM-075 receive orphan drug designation as a treatment for acute myeloid leukemia (AML).
PCM-075 is an oral adenosine triphosphate competitive inhibitor of the serine/threonine Polo-like kinase 1 (PLK1) enzyme, which is overexpressed in hematologic and solid tumor malignancies.
The COMP’s recommendation for PCM-075 is expected to be adopted by the European Commission at the end of this month.
Orphan drug designation in Europe is available to companies developing products intended to treat a life-threatening or chronically debilitating condition that affects fewer than 5 in 10,000 people in the European Union (EU).
The designation allows for financial and regulatory incentives that include 10 years of marketing exclusivity in the EU after product approval, eligibility for conditional marketing authorization, protocol assistance from the European Medicines Agency at reduced fees during the product development phase, and direct access to centralized marketing authorization in the EU.
PCM-075 research
PCM-075 only targets the PLK1 isoform (not PLK2 or PLK3) and has a 24-hour drug half-life with reversible, on-target hematologic toxicities, according to Trovagene, Inc., the company developing PCM-075.
Trovagene believes that PCM-075’s reversible, on-target activity, combined with an improved dose/scheduling protocol, could mean that PCM-075 will improve upon long-term outcomes observed in previous studies with a PLK inhibitor in AML.
This includes a phase 2 study in which AML patients who received a PLK inhibitor plus low-dose cytarabine (LDAC) had a higher response rate than patients who received LDAC alone—31% and 13.3%, respectively.
Trovagene said preclinical studies have shown that PCM-075 synergizes with more than 10 drugs used to treat hematologic and solid tumor malignancies. This includes FLT3 and HDAC inhibitors, taxanes, and cytotoxins.
Trovagene is now conducting a phase 1b/2 trial of PCM-075 in combination with standard care (LDAC or decitabine) in patients with AML (NCT03303339).
The company has already completed a phase 1 dose-escalation study of PCM-075 in patients with advanced metastatic solid tumor malignancies. Results from this study were published in Investigational New Drugs.