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Application Includes Overall Survival Data From Phase 3 TOWER Study to Support Conversion From Accelerated Approval to Full Approval
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Acceptance Reinforces Significant Need for Innovative Treatment Options for Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia
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BLINCYTO is the First-and-Only Approved Bispecific CD19-Directed CD3 T Cell Engager (BiTE®) Immunotherapy
THOUSAND OAKS, CA, USA I March 29, 2017 I Amgen (NASDAQ:AMGN) today announced that the U.S. Food and Drug Administration (FDA) has accepted for priority review the supplemental Biologics License Application (sBLA) for BLINCYTO® (blinatumomab) to include overall survival (OS) data from the Phase 3 TOWER study. The application also includes new data supporting the treatment of patients with Philadelphia chromosome-positive (Ph+) relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). The application aims to expand BLINCYTO’s indication for the treatment of all patients with relapsed or refractory B-cell precursor ALL and supports the conversion of BLINCYTO’s accelerated approval to full approval.
“Patients with relapsed or refractory ALL generally have a very poor prognosis. The median overall survival – or OS – on standard of care chemotherapy is just four months,” said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. “BLINCYTO is the first-and-only approved bispecific immunotherapy with superior OS results versus standard of care chemotherapy, nearly doubling the median OS for patients with this form of ALL. We look forward to making this important potential new option available to patients with all forms of relapsed or refractory B-cell ALL.”
Priority review is assigned to applications for drugs that treat serious conditions and would, if approved, provide significant improvements in the safety or effectiveness of the treatment, diagnosis or prevention of serious conditions. The Prescription Drug User Fee Act (PDUFA) target action date is Aug. 14, 2017.
BLINCYTO, the first-and-only FDA-approved CD19-directed CD3 bispecific T cell engager (BiTE®) antibody, was previously granted breakthrough therapy designation and accelerated approval. It is also the first single-agent immunotherapy approved to treat patients with Philadelphia chromosome-negative (Ph-) relapsed or refractory B-cell precursor ALL.
The application is based on results from the TOWER study, investigating the efficacy of BLINCYTO versus standard of care (SOC) chemotherapy in adult patients with Ph- relapsed or refractory B-cell precursor ALL, which found that BLINCYTO demonstrated a statistically significant improvement in OS over SOC chemotherapy, almost doubling median OS. The study showed that median OS was 7.7 months (95 percent CI: 5.6, 9.6) for BLINCYTO versus four months (95 percent CI: 2.9, 5.3) for SOC (hazard ratio for death=0.71; p=0.012). BLINCYTO more than doubled median OS versus chemotherapy when used early (in first salvage; 11.1 months versus 5.3 months). Per the recommendation of an independent data monitoring committee, Amgen ended the study early for efficacy. These results were presented during the Presidential Symposium at the 21st Congress of the European Hematology Association and published in the New England Journal of Medicine.
Safety results among patients who received BLINCYTO were comparable to those seen in the Phase 2 studies in adult patients with Ph- relapsed or refractory B-cell precursor ALL. For the most common adverse events (greater than or equal to 10 percent incidence rate) in the BLINCYTO arm, only three events (cough, pyrexia, cytokine release syndrome) occurred at an incidence rate that was at least five percent higher for BLINCYTO compared to SOC chemotherapy.
The application also includes data from the ALCANTARA study, evaluating the efficacy and tolerability of BLINCYTO in adult patients with Ph+ relapsed or refractory B-cell precursor ALL, which were published today in the Journal of Clinical Oncology.
The FDA-approved prescribing information for BLINCYTO includes a boxed warning for cytokine release syndrome and neurologic toxicities. BLINCYTO is also under a REMS program in the US.
ALL is a rare and rapidly progressing cancer of the blood and bone marrow.1,2 Currently, there is no broadly accepted standard treatment regimen for adult patients with relapsed or refractory ALL beyond chemotherapy.3 In adult ALL, approximately 75 percent is B-cell precursor ALL, of which 75-80 percent is Ph-, and roughly half will be refractory to treatment or experience relapse.4
About the TOWER Study
The TOWER study was a Phase 3, randomized, active-controlled, open-label study investigating the efficacy of BLINCYTO versus SOC chemotherapy in 405 adult patients with Ph- relapsed or refractory B-cell precursor ALL. The study enrolled a difficult-to-treat patient population which included patients from several stages of relapse, 17 percent of whom had relapsed post-allogenic stem cell transplant (alloSCT), and excluded those with late first relapse (≥ 12 months after initial remission). Patients were randomized in a 2:1 ratio to receive BLINCYTO (n=271) or treatment with investigator choice of one of four protocol-defined SOC chemotherapy regimens (n=134). The primary endpoint was OS. Key secondary endpoints included complete remission within 12 weeks, the combined endpoint of complete remission plus complete remission with partial or incomplete hematologic recovery and event-free survival. Other secondary endpoints included remission duration, minimal residual disease (MRD) remission (<10–4), alloSCT rate and adverse event rates.
The TOWER study is the confirmatory trial for BLINCYTO. Click here to read about the trial on ClinicalTrials.gov.
About the ALCANTARA Study
The ALCANTARA study was a Phase 2, single-arm, multicenter, open-label study investigating the efficacy and tolerability of BLINCYTO in 45 adult patients with Ph+ B-cell precursor ALL, who had relapsed after or were refractory to at least one second-generation or later tyrosine kinase inhibitor (TKI), or were intolerant to second-generation or later TKIs and intolerant or refractory to imatinib. BLINCYTO was administered in 28-day cycles by continuous intravenous infusion. The primary endpoint was complete remission or complete remission with partial hematologic recovery during the first two cycles. Key secondary endpoints included MRD response, rate of alloHSCT, relapsed free survival, OS and adverse events.
Safety results among subjects who received BLINCYTO were comparable to those seen in the Phase 2 studies in adult patients with Ph- relapsed or refractory B-cell precursor ALL.
About BLINCYTO® (blinatumomab)
BLINCYTO is a bispecific CD19-directed CD3 T cell engager (BiTE®) antibody construct that binds specifically to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells.
BLINCYTO was granted breakthrough therapy and priority review designations by the FDA, and is now approved in the U.S. for the treatment of Ph- relapsed or refractory B-cell precursor ALL. This indication is approved under accelerated approval. Continued approval for this indication may be contingent upon verification of clinical benefit in subsequent trials.
In November 2015, BLINCYTO was granted conditional marketing authorization in the EU for the treatment of adults with Ph- relapsed or refractory B-cell precursor ALL.
About BiTE® Technology
Bispecific T cell engager (BiTE®) antibody constructs are a type of immunotherapy being investigated for fighting cancer by helping the body’s immune system to detect and target malignant cells. The modified antibodies are designed to engage two different targets simultaneously, thereby juxtaposing T cells (a type of white blood cell capable of killing other cells perceived as threats) to cancer cells. BiTE® antibody constructs help place the T cells within reach of the targeted cell, with the intent of allowing T cells to inject toxins and trigger the cancer cell to die (apoptosis). BiTE® antibody constructs are currently being investigated for their potential to treat a wide variety of cancers. For more information, visit www.biteantibodies.com.
About Amgen’s Commitment to Oncology
Amgen Oncology is committed to helping patients take on some of the toughest cancers, such as those that have been resistant to drugs, those that progress rapidly through the body and those where limited treatment options exist. Amgen’s supportive care treatments help patients combat certain side effects of strong chemotherapy, and our targeted medicines and immunotherapies focus on more than a dozen different malignancies, ranging from blood cancers to solid tumors. With decades of experience providing therapies for cancer patients, Amgen continues to grow its portfolio of innovative and biosimilar oncology medicines.
About Amgen
Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.
Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people’s lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world’s leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.
For more information, visit www.amgen.com and follow us on www.twitter.com/amgen.
References:
- Cancer Research UK. Acute lymphoblastic leukaemia risks and causes. http://www.cancerresearchuk.org/about-cancer/type/all/about/acute-lymphoblastic-leukaemia-risks-and-causes. Accessed Jan. 13, 2017.
- Mayo Clinic. Acute lymphocytic leukemia. http://www.mayoclinic.com/health/acute-lymphocytic-leukemia/DS00558. Accessed Jan. 13, 2017.
- Davis T, Farag SS. Treating relapsed or refractory Philadelphia chromosome-negative acute lymphoblastic leukemia: liposome-encapsulated vincristine. Int J Nanomedicine. 2013:8 3479-3488.
- Katz AJ, et al. Acute lymphoblastic leukemia: an assessment of international incidence, survival, and disease burden. Cancer Causes Control. 2015;26(11):1627-42.
SOURCE: Amgen
Post Views: 66
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Application Includes Overall Survival Data From Phase 3 TOWER Study to Support Conversion From Accelerated Approval to Full Approval
-
Acceptance Reinforces Significant Need for Innovative Treatment Options for Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia
-
BLINCYTO is the First-and-Only Approved Bispecific CD19-Directed CD3 T Cell Engager (BiTE®) Immunotherapy
THOUSAND OAKS, CA, USA I March 29, 2017 I Amgen (NASDAQ:AMGN) today announced that the U.S. Food and Drug Administration (FDA) has accepted for priority review the supplemental Biologics License Application (sBLA) for BLINCYTO® (blinatumomab) to include overall survival (OS) data from the Phase 3 TOWER study. The application also includes new data supporting the treatment of patients with Philadelphia chromosome-positive (Ph+) relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). The application aims to expand BLINCYTO’s indication for the treatment of all patients with relapsed or refractory B-cell precursor ALL and supports the conversion of BLINCYTO’s accelerated approval to full approval.
“Patients with relapsed or refractory ALL generally have a very poor prognosis. The median overall survival – or OS – on standard of care chemotherapy is just four months,” said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. “BLINCYTO is the first-and-only approved bispecific immunotherapy with superior OS results versus standard of care chemotherapy, nearly doubling the median OS for patients with this form of ALL. We look forward to making this important potential new option available to patients with all forms of relapsed or refractory B-cell ALL.”
Priority review is assigned to applications for drugs that treat serious conditions and would, if approved, provide significant improvements in the safety or effectiveness of the treatment, diagnosis or prevention of serious conditions. The Prescription Drug User Fee Act (PDUFA) target action date is Aug. 14, 2017.
BLINCYTO, the first-and-only FDA-approved CD19-directed CD3 bispecific T cell engager (BiTE®) antibody, was previously granted breakthrough therapy designation and accelerated approval. It is also the first single-agent immunotherapy approved to treat patients with Philadelphia chromosome-negative (Ph-) relapsed or refractory B-cell precursor ALL.
The application is based on results from the TOWER study, investigating the efficacy of BLINCYTO versus standard of care (SOC) chemotherapy in adult patients with Ph- relapsed or refractory B-cell precursor ALL, which found that BLINCYTO demonstrated a statistically significant improvement in OS over SOC chemotherapy, almost doubling median OS. The study showed that median OS was 7.7 months (95 percent CI: 5.6, 9.6) for BLINCYTO versus four months (95 percent CI: 2.9, 5.3) for SOC (hazard ratio for death=0.71; p=0.012). BLINCYTO more than doubled median OS versus chemotherapy when used early (in first salvage; 11.1 months versus 5.3 months). Per the recommendation of an independent data monitoring committee, Amgen ended the study early for efficacy. These results were presented during the Presidential Symposium at the 21st Congress of the European Hematology Association and published in the New England Journal of Medicine.
Safety results among patients who received BLINCYTO were comparable to those seen in the Phase 2 studies in adult patients with Ph- relapsed or refractory B-cell precursor ALL. For the most common adverse events (greater than or equal to 10 percent incidence rate) in the BLINCYTO arm, only three events (cough, pyrexia, cytokine release syndrome) occurred at an incidence rate that was at least five percent higher for BLINCYTO compared to SOC chemotherapy.
The application also includes data from the ALCANTARA study, evaluating the efficacy and tolerability of BLINCYTO in adult patients with Ph+ relapsed or refractory B-cell precursor ALL, which were published today in the Journal of Clinical Oncology.
The FDA-approved prescribing information for BLINCYTO includes a boxed warning for cytokine release syndrome and neurologic toxicities. BLINCYTO is also under a REMS program in the US.
ALL is a rare and rapidly progressing cancer of the blood and bone marrow.1,2 Currently, there is no broadly accepted standard treatment regimen for adult patients with relapsed or refractory ALL beyond chemotherapy.3 In adult ALL, approximately 75 percent is B-cell precursor ALL, of which 75-80 percent is Ph-, and roughly half will be refractory to treatment or experience relapse.4
About the TOWER Study
The TOWER study was a Phase 3, randomized, active-controlled, open-label study investigating the efficacy of BLINCYTO versus SOC chemotherapy in 405 adult patients with Ph- relapsed or refractory B-cell precursor ALL. The study enrolled a difficult-to-treat patient population which included patients from several stages of relapse, 17 percent of whom had relapsed post-allogenic stem cell transplant (alloSCT), and excluded those with late first relapse (≥ 12 months after initial remission). Patients were randomized in a 2:1 ratio to receive BLINCYTO (n=271) or treatment with investigator choice of one of four protocol-defined SOC chemotherapy regimens (n=134). The primary endpoint was OS. Key secondary endpoints included complete remission within 12 weeks, the combined endpoint of complete remission plus complete remission with partial or incomplete hematologic recovery and event-free survival. Other secondary endpoints included remission duration, minimal residual disease (MRD) remission (<10–4), alloSCT rate and adverse event rates.
The TOWER study is the confirmatory trial for BLINCYTO. Click here to read about the trial on ClinicalTrials.gov.
About the ALCANTARA Study
The ALCANTARA study was a Phase 2, single-arm, multicenter, open-label study investigating the efficacy and tolerability of BLINCYTO in 45 adult patients with Ph+ B-cell precursor ALL, who had relapsed after or were refractory to at least one second-generation or later tyrosine kinase inhibitor (TKI), or were intolerant to second-generation or later TKIs and intolerant or refractory to imatinib. BLINCYTO was administered in 28-day cycles by continuous intravenous infusion. The primary endpoint was complete remission or complete remission with partial hematologic recovery during the first two cycles. Key secondary endpoints included MRD response, rate of alloHSCT, relapsed free survival, OS and adverse events.
Safety results among subjects who received BLINCYTO were comparable to those seen in the Phase 2 studies in adult patients with Ph- relapsed or refractory B-cell precursor ALL.
About BLINCYTO® (blinatumomab)
BLINCYTO is a bispecific CD19-directed CD3 T cell engager (BiTE®) antibody construct that binds specifically to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells.
BLINCYTO was granted breakthrough therapy and priority review designations by the FDA, and is now approved in the U.S. for the treatment of Ph- relapsed or refractory B-cell precursor ALL. This indication is approved under accelerated approval. Continued approval for this indication may be contingent upon verification of clinical benefit in subsequent trials.
In November 2015, BLINCYTO was granted conditional marketing authorization in the EU for the treatment of adults with Ph- relapsed or refractory B-cell precursor ALL.
About BiTE® Technology
Bispecific T cell engager (BiTE®) antibody constructs are a type of immunotherapy being investigated for fighting cancer by helping the body’s immune system to detect and target malignant cells. The modified antibodies are designed to engage two different targets simultaneously, thereby juxtaposing T cells (a type of white blood cell capable of killing other cells perceived as threats) to cancer cells. BiTE® antibody constructs help place the T cells within reach of the targeted cell, with the intent of allowing T cells to inject toxins and trigger the cancer cell to die (apoptosis). BiTE® antibody constructs are currently being investigated for their potential to treat a wide variety of cancers. For more information, visit www.biteantibodies.com.
About Amgen’s Commitment to Oncology
Amgen Oncology is committed to helping patients take on some of the toughest cancers, such as those that have been resistant to drugs, those that progress rapidly through the body and those where limited treatment options exist. Amgen’s supportive care treatments help patients combat certain side effects of strong chemotherapy, and our targeted medicines and immunotherapies focus on more than a dozen different malignancies, ranging from blood cancers to solid tumors. With decades of experience providing therapies for cancer patients, Amgen continues to grow its portfolio of innovative and biosimilar oncology medicines.
About Amgen
Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.
Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people’s lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world’s leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.
For more information, visit www.amgen.com and follow us on www.twitter.com/amgen.
References:
- Cancer Research UK. Acute lymphoblastic leukaemia risks and causes. http://www.cancerresearchuk.org/about-cancer/type/all/about/acute-lymphoblastic-leukaemia-risks-and-causes. Accessed Jan. 13, 2017.
- Mayo Clinic. Acute lymphocytic leukemia. http://www.mayoclinic.com/health/acute-lymphocytic-leukemia/DS00558. Accessed Jan. 13, 2017.
- Davis T, Farag SS. Treating relapsed or refractory Philadelphia chromosome-negative acute lymphoblastic leukemia: liposome-encapsulated vincristine. Int J Nanomedicine. 2013:8 3479-3488.
- Katz AJ, et al. Acute lymphoblastic leukemia: an assessment of international incidence, survival, and disease burden. Cancer Causes Control. 2015;26(11):1627-42.
SOURCE: Amgen
Post Views: 66
