EC grants orphan drug status to Trovagene’s Onvansertib for AML treatment

Onvansertib is a first-in-class, third generation, oral and highly-selective Polo-like Kinase 1 (PLK1) inhibitor.

Trovagene executive chairman Dr Thomas Adams said: “The European Commission’s decision to grant orphan drug designation to Onvanersertib for the treatment of AML is a key regulatory milestone that will further facilitate our clinical development program.

“We believe that Onvansertib, which previously received orphan drug designation for the treatment of AML from the FDA in the U.S., has the potential to provide a much-needed new therapeutic option for patients who are ineligible for induction therapy or who have relapsed/refractory disease.”

Orphan drug designation by the EC provides regulatory and financial incentives to Trovagene, including reduced fees during the product development phase, direct access to centralized marketing authorization in the EU, and 10-year market exclusivity following product approval.

The COMP, a committee of the EMA, adopted a positive opinion on the granting of orphan drug designation to Onvansertib in July, 2018, stating that “Onvansertib will be of significant benefit to those affected by AML.”

Following the process set forth by the EMA, the opinion of the COMP was subsequently submitted to the European Commission (EC) for formal endorsement. The EC decision to endorse the positive opinion issued by the COMP was received by Trovagene on August 28, 2018.

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy in which myeloid lineage cells of the bone marrow cease to differentiate appropriately, resulting in a marked increase in the number of circulating immature blast cells.

As a consequence, the counts of mature red blood cells, platelets, and normal white blood cells decline, causing fatigue, shortness of breath, bleeding, and increased susceptibility to infection. The incidence is estimated to be approximately 18,000 new cases annually in the EU and is on the rise due to the aging population. The five-year survival rate is approximately 22%.

Onvansertib is a first-in-class, 3rd generation, oral and highly-selective adenosine triphosphate (ATP) competitive inhibitor of the serine/threonine polo-like-kinase 1 (PLK 1) enzyme, which is over-expressed in multiple cancers, including leukemias, lymphomas and solid tumors.

Separate studies with other PLK inhibitors have shown that inhibition of polo-like-kinases can lead to tumor cell death, including a Phase 2 study in Acute Myeloid Leukemia (AML) where response rates of up to 31% were observed when combined with a standard therapy for AML (low-dose cytarabine-LDAC) versus treatment with LDAC alone with a 13.3% response rate.

A Phase 1 open-label, dose escalation safety study of Onvansertib has been completed in patients with advanced metastatic solid tumor cancers and published in Investigational New Drugs. The maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) in this trial was 24 mg/m2.

Trovagene has an ongoing Phase 1b/2 clinical trial with Onvansertib in AML that was accepted by the National Library of Medicine (NLM).

The NCT number assigned by clinicaltrials.gov for this study is NCT03303339. Onvansertib has been granted Orphan Drug Designation by the FDA in the U.S. and by the EC in the European Union (EU) for the treatment of patients with AML.

Onvansertib targets the PLK1 isoform (not PLK2 or PLK3), is orally available, has a 24-hour drug half-life with only mild to moderate side effects reported. Trovagene believes that targeting only PLK1 and having a favorable safety and tolerability profile, along with an improved dose/scheduling regimen will significantly improve on the outcome observed in previous studies with a former panPLK inhibitor in AML.

Onvansertib has demonstrated synergy in preclinical studies with numerous chemotherapies and targeted therapeutics used to treat leukemias, lymphomas and solid tumor cancers, including FLT3 and HDAC inhibitors, taxanes, and cytotoxins.

Trovagene believes the combination of its targeted PLK1 inhibitor, Onvansertib, with other compounds has the potential to improve clinical efficacy in Acute Myeloid Leukemia (AML), metastatic Castration-Resistant Prostate Cancer (mCRPC), Non-Hodgkin Lymphoma (NHL), Triple Negative Breast Cancer (TNBC), as well as other types of cancer.

Source: Company Press Release