The novel P-gp inhibitor encequidar (formerly known as HM30181A) forms the cornerstone of our Orascovery platform. Encequidar enables the oral absorption of a wide range of effective anticancer drugs, which can currently only be given intravenously, due to poor oral absorption.
P-glycoprotein (P-gp) is an active transport protein on the surface of the gastrointestinal (GI) tract. Many anticancer drugs are substrates of P-gp, and when orally administered, they will be pumped back into the GI tract, thereby limiting the drugs to intravenous administration. Encequidar, as a selective and potent P-gp inhibitor, has the potential to allow oral delivery of these chemotherapy agents. Current clinical trials are underway globally with encequidar combined with paclitaxel, docetaxel, irinotecan, eribulin, and topotecan.
Encequidar is a novel compound with inhibitory activity specific to P-gp. Encequidar’s distinguishing feature is its minimal oral absorption. This feature localizes P-gp inhibitory activity in the GI tract, improving the absorption of chemotherapy agents, but limiting the potential for unnecessary P-gp inhibition at other places in the body.
We believe the Orascovery approach will establish a new paradigm in the use of oral anticancer drugs.
Oral paclitaxel and encequidar
Paclitaxel is a widely used IV administered tubulin-stabilizing chemotherapeutic agent. By administering paclitaxel orally with encequidar, we have been able to achieve similar paclitaxel exposures compared to the widely used 80 mg/m² IV weekly dosing regimen.
Current clinical data suggests the potential of a better clinical response and tolerability profile, which can likely be attributed to the better pharmacokinetic profile achieved. Additionally, oral paclitaxel and encequidar may offer patients with paclitaxel-responsive tumors freedom from the burden of infusion clinic visits, premedication, and potentially dangerous infusion-related hypersensitivity-type reactions. Oral paclitaxel and encequidar has completed a Phase 3 pivotal trial in metastatic breast cancer, with several additional on-going clinical studies as monotherapy and in combination with other proven anticancer agents.
Oral paclitaxel and encequidar
Paclitaxel is a widely used IV administered tubulin-stabilizing chemotherapeutic agent. By administering paclitaxel orally with encequidar, we have been able to achieve similar paclitaxel exposures compared to the widely used 80 mg/m² IV weekly dosing regimen.
Oral irinotecan and encequidar
Irinotecan is an anticancer agent, currently approved only for IV administration, that is used widely in the treatment of colorectal, lung, ovarian, cervical, pancreatic, upper gastrointestinal and brain cancer.
Oral irinotecan and encequidar is ready to advance to and preparing for Phase 2.
Oral docetaxel and encequidar
Docetaxel is an anticancer agent, currently approved only for IV administration, that is used widely in the treatment of breast, prostate, gastric, head and neck, and lung cancer.
Oral docetaxel and encequidar is ready to advance to and preparing for Phase 2.
Oral topotecan and encequidar
Topotecan is an anticancer agent that is used in the treatment of ovarian, cervical and small cell lung cancers.
Oral topotecan and encequidar is currently in Phase 1 clinical studies.
Oral eribulin and encequidar
Eribulin is an anticancer agent that inhibits the growth phase of cells. Intravenous eribulin (Halaven®) is approved by the FDA in to treat patients with metastatic breast cancer who have previously received at least 2 chemotherapeutic regimens for the treatment of metastatic disease, and to treat patients with unresectable or metastatic liposarcoma who have received a prior anthracycline-containing regimen. Notably, Halaven® has shown to provide responses in patients with tumors resistant to other microtubule-targeting drugs.
The U.S. FDA allowed our Investigational New Drug Application (IND) in October 2018. Phase 1 studies of oral eribulin and encequidar are currently underway.
Source: Athenex