ATLANTA — At this year's annual meeting of the American Society for Hematology (Washington), the distinction of having an abstract selected for the scientific plenary session went to Amgen (Thousand Oaks, California).
The company presented the results of two Phase III studies and an extension study on its AMG-531 for the bleeding disorder idiopathic thrombocytopenic purpura and Phase III data from splenectomized patients were presented in the plenary session. Thrombocytopenia, or low platelet count, can be the consequence of a number of disease states — or their treatments, such as chemotherapy. In the autoimmune condition idiopathic thrombocytopenic purpura, the primary problem is that platelets are coated with autoantibodies and destroyed by the immune system, but there are also fewer platelets than normal being produced in the first place.
AMG-531 works by increasing both the production of platelets and their circulation time in the blood; the drug is a combination of a peptide sequence that stimulates the TPO receptor, leading to increased platelet production, and an antibody that prevents the peptide from being degraded. The peptide sequence of AMG-531 has no homology to endogenous thrombopoietin, making it less likely that patients will develop antibodies to it; indeed, only one patient developed such antibodies, and they disappeared after discontinuing the drug.
Amgen reported results from two separate studies, with patients whose spleen had or had not been removed. In both studies, patients received weekly doses of AMG-531 for 24 weeks. Platelet levels were monitored throughout the study and for 12 weeks afterward. The overall response rate was nearly 80% for splenectomized and nearly 90% for non-splenectomized patients.
All patients taking AMG-531 were able to either eliminate or reduce concurrent medications. Bleeding occurred at the same rate in treatment and control groups, prompting one speaker to wonder during the question-and-ansswer session whether the platelets were functional. But presenter James Bussel said that bleeding was euqivalent "because we don't let patients bleed" — instead, patients receive so-called rescue medication when their platelet counts fall to dangerously low levels.
The company also presented interim data from a long-term extension study that has followed some patients for over two years. Though a few patients sustained the increase in platelet levels when they are no longer taking the drug, this is not the norm; presenting data from the splenectomized patients at the Sunday plenary, presenter Terry Gernsheimer, said that platelet counts usually fell within a few weeks after the drug was discontinued.
In other reports from the meeting:
- Bayer Healthcare (Leverkusen, Germany) and Johnson & Johnson Pharmaceutical Research & Development (New Brunswick, New Jersey), said Phase III clinical trial results underscored that rivaroxaban, the oral, once-daily, investigational anticoagulant, was significantly more effective than enoxaparin, the standard of care, in preventing venous thromboembolism in patients undergoing total hip or knee replacement surgery. Rivaroxaban-treated patients consistently experienced lower rates of VTE events compared to enoxaparin-treated patients across three large studies as well as demonstrating a similar rate of major bleeding events.
- Pharmion (Boulder, Colorado) reported interim data from a Phase II clinical trial evaluating three alternative five-day dosing schedules for Vidaza (azacitidine for injection) that demonstrated safety and response profiles consistent with those achieved with the FDA-approved seven-day regimen, as reflected in rates of hematologic improvement (HI) and red blood cell (RBC) transfusion independence. The company said the data suggest that a five-day schedule is as effective as the currently approved seven-day schedule at achieving RBC transfusion independence and hematologic improvement in MDS patients.
- ProMetic Life Sciences (Montreal) said a Phase II trial of its investigational compound PBI-1402 induced a significant increase in red blood cell count and hemoglobin level in patients with chemotherapy-induced anemia. No significant adverse events were observed. PBI-1402 is a novel, orally active low molecular weight synthetic compound with erythropoiesis-stimulating activity via a mechanism of action distinct from erythropoietin.
- ThromboGenics (Leuven, Belgium), unveiled results of the first Phase I trial of TB-402, a recombinant human monoclonal antibody which has shown a beneficial partial inhibition of the blood coagulation Factor VIII. The randomized, single-dose, placebo-controlled, dose escalation trial in healthy male volunteers show that TB-402 is both safe and well-tolerated and no serious adverse events were reported. In addition, there were no major bleeding complications, with the overall incidence being similar in both the TB-402 treated group and the patients who received placebo. The compound will now move into Phase II development.