Therapeutics
Anemia – PBI 1402
ProMetic’s lead candidate drug, PBI-1402, addresses substantial unmet medical needs.
- PBI-1402 is orally active, whereas most other drugs treating anemia are injectables.
- PBI-1402 has shown anticancer activity in multiple pre-clinical models.
- PBI-1402, all the while mimicking EPO’s biological activity, has a distinct mechanism of action from EPO, as it does not bind to the same cell surface receptor as EPO. It therefore provides great promise of serving as a stand-alone therapeutic in the treatment of patients with anemia.
- PBI-1402 is an affordable low molecular weight synthetic candidate drug, relative to costly recombinant proteins, such as EPO.
- PBI-1402 addresses a worldwide marketplace that exceeds $15 billion.
PBI-1402 for the treatment of Anemia indications
The initial indication targeted by PBI-1402 is anemia in cancer patients undergoing chemotherapy. Upwards of two thirds of cancer patients treated with chemotherapy develop anemia. Treatment with EPO, the current drug of choice for this indication, is active in only 50 to 60 percent of these patients.
PBI-1402 has reported positive clinical results in the chemotherapy-induced anemia trial and demonstrated excellent safety and tolerability, as well as an impressive efficacy profile. A Phase II trial of PBI-1402 demonstrated a significant increase in the red blood cell count and the hemoglobin level in patients with chemotherapy-induced anemia (“CIA”). In this open-label Phase II trial, patients each received PBI-1402 once daily at doses ranging from 44mg/kg to 88mg/kg. Analysis of the data showed that only 2 patients out of 28 (7%) treated with PBI-1402 required a RBC transfusion, a response rate greater than 90% with regards to this clinical objective. In the March 13, 2008 FDA briefing document, the Oncology Drugs Advisory Committee emphasizes that the primary objective of treating CIA patients with erythropoiesis-stimulating agents (“ESAs”) as being the ability to reduce the need for RBC transfusion. The Advisory Committee cites that approximately 50% of anemic patients receiving chemotherapy required RBC transfusion, and 20%-25% of patients treated with ESAs still required RBC transfusions.
The encouraging positive results from the CIA clinical trial and the anticancer effects reported in animal models seem to indicate that PBI-1402 is well suited for the treatment of anemia in oncology, resulting in the PBI-1402 clinical platform being extended to patients suffering from cancer-related anemia. Moreover, approximately twenty million patients in the U.S. alone are diagnosed with chronic kidney diseases (“CKD”). Patients diagnosed at severe CKD stages (3 and 4) often develop anemia before they require hemodialysis. CKD patients still at the pre-dialysis stage could greatly benefit from an orally administered drug as a treatment for their anemia.
Recent experiments based on a 5/6 nephrectomized rat model have demonstrated the ability of PBI-1402 to correct anemia. This model simulates chronic renal failure in humans, a condition whereby the kidneys fail to produce sufficient EPO for the stimulation of red blood cell production. These results indicate additional potential for PBI-1402.