Trovagene announced the U.S. Food and Drug Administration (FDA) granted an orphan drug designation to PCM-075 for the treatment of patients with acute myeloid leukemia (AML) on September 28, 2017. PCM-075 is an oral, highly-selective adenosine triphosphate (ATP) competitive inhibitor of the serine/threonine Polo-like Kinase 1 (PLK1) enzyme, which appears to be over expressed in several different hematologic malignancies and solid tumor cancers.
"AML is an aggressive cancer of the blood and bone marrow with approximately 20,000 new cases in the U.S each year," said Bill Welch, Chief Executive Officer of Trovagene. "We see the FDA's granting of orphan drug designation for PCM-075 as underscoring the medical need for new therapies for patients with AML and an important step forward in our clinical development program."
Orphan drug designation is granted by the FDA to drugs that are intended treat rare diseases or conditions for patients in the U.S. The orphan drug designation allows the orphan drug indication for the drug to be eligible for a seven-year period of U.S. marketing exclusivity upon approval of the drug, as well as other development assistance and financial incentives.
Trovagene is initiating a Phase 1b/2 open-label trial to evaluate the safety and anti-leukemic activity of PCM-075 in combination with standard-of-care in patients with AML, at ten research sites across the U.S., led by Hematologist Dr. Jorge Cortes, Deputy Department Chair, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center.
Acute myeloid leukemia (AML) is a 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 Surveillance, Epidemiology and End Results (SEER) program estimates the annual incidence rate of AML in the United States to be approximately 21,000 cases in 2017. Rates of new AML cases have been rising an average of 3.1% each year over the last 10 years. The median age of AML diagnosis is 68 years of age, and approximately 45% of new diagnoses are among patients age 70 years or older.
PCM-075 is a highly-selective adenosine triphosphate (ATP) competitive inhibitor of the serine/threonine polo-like-kinase 1 (PLK 1) enzyme, which is over-expressed in multiple hematologic and solid tumor cancers. Studies 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 up to 31% were observed when used in conjunction 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 PCM-075 has been completed in patients with advanced metastatic solid tumor cancers, and published in Investigational New Drugs. Trovagene plans to initiate a Phase 1b/2 clinical trial with PCM-075 in AML, since it has shown significant advantages over prior PLK1 inhibitors evaluated in this indication, including a higher selectivity, greater potency, oral bioavailability and shorter half-life. This study was accepted by the National Library of Medicine (NLM) and is now publicly viewable on www.clinicaltrials.gov. The NCT number assigned by clinicaltrials.gov for this study is NCT03303339. PCM-075 has demonstrated synergy in preclinical studies with over 10 chemotherapeutic and target agents used in hematologic and solid tumor cancers, including FLT3 and HDAC inhibitors, taxanes, and cytotoxins. Trovagene believes the combination of its targeted PLK-1 inhibitor, PCM-075, with other compounds has the potential for improved clinical efficacy in Acute Myeloid Leukemia (AML), Castration-Resistant Prostate Cancer (CRPC), Non-Hodgkin Lymphoma (NHL), Triple Negative Breast Cancer (TNBC) and Adrenocortical Carcinoma (ACC).