Date: 2014-06-13
Type of information: Presentation of results at a congress
phase: 2a
Announcement: presentation of results at the 19th Congress of the European Hematology Association (EHA) in Milan, Italy
Company: Noxxon Pharma (Germany
Product: olaptesed pegol (NOX-A12 anti-CXCL12/SDF-1 (CXC Chemokine Ligand 12 / Stromal Cell-Derived Factor-1) Spiegelmer®
Action
mechanism: Olaptesed pegol/NOX-A12 specifically antagonizes CXCL12/SDF-1 (CXC Chemokine Ligand 12 / Stromal Cell-Derived Factor-1), a chemokine which attracts and activates immune and non-immune cells including stem cells from the bone marrow. CXCL12 binds with high affinity to two chemokine receptors, CXCR4 and CXCR7. The CXCL12 / CXCR4 / CXCR7 axis has been shown to play a role in stem cell mobilization, vasculogenesis, tumor growth and metastasis. CXCL12 signaling has been shown to play an important role in the pathophysiology of CLL, especially in the interaction of leukemic cells with the tissue microenvironment. The therapeutic concept of NOX-A12 is to inhibit such tumor-supporting interactions and thereby sensitize CLL cells to chemotherapy.
Disease: multiple myeloma
Therapeutic area: Cancer - Oncology
Country: Europe
Trial
details: NOXXON’s multi-center, open-label, uncontrolled study will be conducted in Europe on 28 relapsed multiple myeloma patients who were all previously treated for their cancer. The patients will receive NOX-A12 in combination with a background therapy of Velcade®/bortezomib and dexamethasone (VD). Combination treatment with NOX-A12 and VD will occur in 8 cycles of 21 days, with a follow-up period of one year. Each patient will receive up to three different doses of NOX-A12 as part of an individualized dose titration. The primary efficacy endpoint of the study will be the overall response rate, which includes patients with complete and partial responses to therapy.
Latest
news: * On June 13, 2014, NOXXON Pharma presented updated interim data sets from two independent clinical Phase IIa studies of the anti-CXCL12/SDF-1 Spiegelmer® olaptesed pegol (NOX-A12) at the 19th Congress of the European Hematology Association (EHA) in Milan, Italy, from 12-15 June 2014. In a study in 28 relapsed multiple myeloma (MM) patients, olaptesed pegol was combined with Velcade®/bortezomib and dexamethasone (VD). Olaptesed pegol demonstrated effective and long-lasting mobilization of plasma cells into the peripheral blood. Data from 20 patients showed an overall response rate (ORR) of 70% with 6 patients achieving very good partial responses (VGPR) and 8 achieving a partial response, which compares favorably with published data on therapy with VD. Importantly, treatment with olaptesed pegol was not associated with additional toxicity on top of VD. Considering that the study population included patients retreated with bortezomib and a marked proportion of patients with unfavorable cytogenetics, these results support further development of olaptesed pegol in MM. An additional preclinical study on olaptesed pegol suggests that targeting CXCL12 might prevent multiple myeloma cell dissemination to distant bone marrow niches and transition from MGUS (micrometastatic-stage) to active-MM (macrometastatic-stage). The abstracts are entitled: INTERIM RESULTS FROM A PHASE IIA STUDY OF THE ANTI-CXCL12 SPIEGELMER® OLAPTESED PEGOL (NOX-A12) IN COMBINATION WITH BORTEZOMIB AND DEXAMETHASONE IN PATIENTS WITH MULTIPLE MYELOMA. Heinz Ludwig, Katja Weisel, Maria T. Petrucci, Xavier Leleu, Anna M. Cafro, Martin Kropff, Richard Greil, Niklas Zojer, Thomas Dümmler, Anna Kruschinski, Kai Riecke, Robin Foa, Ibrahim Yakoub-Agha, Monika Engelhardt. Abstract P376. and THE ANTI-HEPCIDIN SPIEGELMER® LEXAPTEPID PEGOL (NOX-H94) AS TREATMENT OF ANEMIA OF CHRONIC DISEASE IN PATIENTS WITH MULTIPLE MYELOMA, LOW GRADE LYMPHOMA, AND CLL: A PHASE II PILOT STUDY. Pencho Georgiev, Mihaela Lazaroiu, Luminita Ocroteala, Janet Grudeva-Popova, Emanuil Gheorghita, Mariana Vasilica, Sanda Popescu, Andrei Cucuianu, Luciana Summo, Stéphanie Vauléon, Stefan Zöllner, Frank Schwoebel, Kai Riecke, Heinz Ludwig. Abstract P1172. * On December 9, 2013, Noxxon Pharma has disclosed interim data from two independent clinical phase IIa studies of the anti-CXCL12/SDF-1 Spiegelmer olaptesed pegol (NOX-A12) at the 55th annual meeting of the American Society of Hematology (ASH) in New Orleans, LA, USA from 7-10 December 2013. In the second study, olaptesed was combined with bortezomib and dexamethasone in patients with relapsed multiple myeloma (MM). Data from the 9 patient pilot groups were presented. In patients with relapsed MM, anti-CXCL12/SDF-1 Spiegelmer olaptesed showed the same effect of mobilization of plasma cells into the peripheral blood. In addition, an overall response rate (ORR) of 67% including 22% very good partial responses (vgPR) was achieved in this pilot group. Importantly, treatment with olaptesed was not associated with additional toxicity on top of Velcade®/bortezomib and dexamethasone (VD). If these preliminary results can be maintained in the total sample of 28 patients, then again further development of this novel anti-CXCL12/SDF-1 Spiegelmer will be warranted. (Poster presentations and abstracts: Anti-CXCL12/SDF-1 Spiegelmer NOX-A12 Alone and In Combination with Bortezomib and Dexamethasone In Patients With Relapsed Multiple Myeloma: Results From A Phase IIa Study. Heinz Ludwig, Katja Weisel, Monika Engelhardt, Richard Greil, Anna Maria Cafro, Maria Teresa Petrucci, Thomas Dümmler, Stefan Zöllner, Stefan Zeitler, Kai Riecke, Anna Kruschinski - Targeting the Protective Microenvironment in Multiple Myeloma (MM): An Analysis of The CXCL12/CXCR4-Axis and its Inhibitors AMD3100 and NOX-A12 Combined with Antimyeloma Substances, Such As Pomalidomide and Carfilzomib. Anna Simon, Dagmar Wider, Marie Follo, Johannes Waldschmidt, Martina Kleber, Ralph Waesch, Monika Engelhardt. * On September 26, 2012, Noxxon Pharma has announced the treatment of the first cohort of three multiple myeloma (MM) patients in a Phase IIa clinical trial of its anti-CXCL12/SDF-1 (CXC chemokine ligand 12 / Stromal Cell-Derived Factor-1) Spiegelmer® NOX-A12. CXCL12 signaling has been shown to play an important role in the pathophysiology of MM, especially in the interaction of MM cells with the bone marrow microenvironment. By inhibiting this interaction NOX-A12 sensitizes the cancer cells to chemotherapy. Noxxon expects interim results to be available by the end of 2012.
