Æterna Zentaris Partner, Keryx, Reports Updated Phase 1/2 Data, Including New
Survival Data, on Perifosine (KRX-0401) in the Treatment of Advanced Multiple
Myeloma at the 51st Annual Meeting of the American Society of Hematology
Response Rate Increases to 41% and Median Overall Survival Reported at 25 Months for All Evaluable Patients
Trial Results
Eighty-four patients with relapsed/refractory multiple myeloma were enrolled in a combined Phase 1/2 study (18 patients in the Phase 1 component and 66 patients in the Phase 2 component). The patients enrolled were heavily pre-treated with a median of 5 prior lines of therapy (range 1 - 13), including:
- 100% of patients had been treated with bortezomib (55% of the patients were previously treated with at least two bortezomib-based therapies (range 1 - 4) and 81% were previously treated with bortezomib plus dexamethasone); - 98% of patients were previously treated with dexamethasone; - 94% of patients were previously treated with lenalidomide (Revlimid(R)) and/or thalidomide (Thalomid(R)); and - 58% of patients had prior stem cell transplant.
Overall Response Rate (ORR), defined as the percentage of patients achieving a complete, partial or minor response (CR, PR or MR), was the primary endpoint, with Time to Progression (TTP), Progression-Free Survival (PFS), Overall Survival (OS) and Safety as secondary endpoints.
Seventy-three patients were evaluable for efficacy. Evaluable patients are defined as those patients who had received at least two cycles of therapy on the combination of perifosine with bortezomib. Of the 73 evaluable patients, 53 patients (73%) were previously refractory to bortezomib (defined as progression on or within 60 days of treatment to a bortezomib-based regimen), including 44 patients who were refractory to the combination of bortezomib + dexamethasone. Twenty evaluable patients (27%) were relapsed to a prior bortezomib-based regimen. Best response for all 73 evaluable patients was as follows:
------------------------------------------------------------------------- Evaluable Patients CR/nCR* PR MR ORR SD(xx) ------------------------------------------------------------------------- All Evaluable Patients (n=73) 3 4% 13 18% 14 19% 30 41% 30 41% ------------------------------------------------------------------------- Bortezomib Relapsed (n=20) 2 10% 7 35% 4 20% 13 65% 7 35% ------------------------------------------------------------------------- Bortezomib Refractory (n=53) 1 2% 6 11% 10 19% 17 32% 23 43% ------------------------------------------------------------------------- * nCR = Near Complete Response is defined as meeting the criteria for CR (non-detectable monoclonal protein by serum and urine), except with detectable monoclonal protein by immunofixation. (xx) SD = Stable Disease for a minimum of 3 months.
Approximately 60% (45 / 73) of patients demonstrated progression (or SD for 4 cycles) at some point in their treatment and received 20 mg dexamethasone, four times per week, in addition to perifosine plus bortezomib. Responses occurred both with patients taking perifosine in combination with bortezomib and with patients receiving the combination plus dexamethasone. Best response for each group was as follows:
------------------------------------------------------------------------- Best Response CR/nCR PR MR ORR SD ------------------------------------------------------------------------- Perifosine + Bortezomib (n=73) 2 3% 10 14% 6 8% 18 25% 19 26% ------------------------------------------------------------------------- Dexamethasone added (n=45) 1 2% 6 13% 10 23% 17 38% 14 31% -------------------------------------------------------------------------
Five patients achieved an initial response on perifosine + bortezomib alone, and subsequently responded again with the addition of dexamethasone. Three additional patients achieved stable disease on perifosine + bortezomib alone, and subsequently achieved stable disease again with the addition of dexamethasone.
Reported for the first time was median Progression-Free Survival (PFS) and Overall Survival (OS) data for all evaluable patients, as follows:
------------------------------------------------------------------------- Evaluable Patients Median PFS* Median OS(xx) ------------------------------------------------------------------------- All Evaluable 6.4 months 25 months Patients 95% CI (5.3, 7.1) 95% CI (15.5, NR) (n=73) ------------------------------------------------------------------------- NR = Not Reached * Median PFS and median TTP were identical, as no patient deaths occurred prior to progression. (xx) Kaplan Meier methodology was used to determine overall survival figures.
Of particular interest was the comparison of evaluable patients who were previously refractory and the patients who were relapsed to a bortezomib-based regimen.
Median PFS and OS for bortezomib relapsed vs. refractory were as follows: ------------------------------------------------------------------------- Bortezomib Relapsed vs. Refractory Median PFS* Median OS(xx) ------------------------------------------------------------------------- Bortezomib Relapsed 8.8 months Not Reached at (n=20) 95% CI (6.3, 11.2) 38+ months 95% CI (25, NR) ------------------------------------------------------------------------- Bortezomib Refractory 5.7 months 22.5 months (n=53) 95% CI (4.3, 6.4) 95% CI (12.3, NR) ------------------------------------------------------------------------- * Median PFS and median TTP were identical, as no patient deaths occurred prior to progression. (xx) Kaplan Meier methodology was used to determine overall survival figures.
No unexpected adverse events have been observed. Toxicities were manageable with supportive care.
"We congratulate our partner Keryx and their principle investigators
Keryx has been granted a Special Protocol Assessment (SPA) from the FDA for the upcoming Phase 3 study of perifosine in multiple myeloma. Additionally, the FDA has granted perifosine Orphan Drug and Fast Track designations in this indication.
About Perifosine (KRX-0401)
Perifosine is a novel oral anticancer agent that modulates several key signal transduction pathways, including Akt, MAPK, and JNK that have been shown to be critical for the survival of cancer cells. Perifosine has demonstrated both safety and clinical efficacy in several tumor types, both as a single agent and in combination with novel therapies. Perifosine is currently in Phase 2 clinical development for multiple tumor types, with a Phase 3 in multiple myeloma, under Special Protocol Assessment (SPA), pending commencement by year-end. Perifosine has also received Orphan Drug designation from the U.S. Food and Drug Administration (FDA) for the treatment of multiple myeloma.
About Multiple Myeloma
Multiple myeloma, a cancer of the plasma cell, is an incurable but treatable disease. Multiple myeloma is the second most-common hematologic cancer, representing 1% of all cancer diagnoses and 2% of all cancer deaths. According to the American Cancer Society, in 2009 there will be an estimated 20,580 new cases of multiple myeloma and an estimated 10,500 deaths from multiple myeloma in the
About Æterna Zentaris Inc.
Æterna Zentaris Inc. is a global biopharmaceutical company focused on endocrine therapy and oncology, with proven expertise in drug discovery, development and commercialization. News releases and additional information are available at www.aezsinc.com.
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