– TIBSOVO® is the First and Only Therapy Approved for Newly Diagnosed AML Patients with an IDH1 Mutation who are Ineligible for Intensive Chemotherapy –
– sNDA Approval Based on 28 Newly Diagnosed Patients from Phase 1 Study of TIBSOVO® in Advanced Hematologic Malignancies with an IDH1 Mutation1 –
– Single Agent TIBSOVO® Demonstrated CR Rate of 28.6% and CR+CRh Rate of 42.9%1 –
CAMBRIDGE, MA, USA I May 02, 2019 I Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases, today announced the U.S. Food and Drug Administration (FDA) approved a supplemental New Drug Application (sNDA) to update the U.S. Prescribing Information for TIBSOVO®, an isocitrate dehydrogenase-1 (IDH1) inhibitor, to include adult patients with newly diagnosed acute myeloid leukemia (AML) with a susceptible IDH1 mutation as detected by an FDA-approved test who are ≥ 75 years old or who have comorbidities that preclude use of intensive induction chemotherapy. The sNDA was granted Priority Review and accepted under the FDA’s Real-Time Oncology Review pilot program, which aims to make the review of oncology drugs more efficient by allowing the FDA access to clinical trial data before the information is formally submitted to the agency. TIBSOVO® received initial FDA approval in July 2018 for adult patients with relapsed or refractory (R/R) AML and an IDH1 mutation1.
“Despite several new AML medicines approved in the last two years, many newly diagnosed patients are still not eligible for existing therapies or combination regimens because of age and other comorbidities,” said Chris Bowden, M.D., chief medical officer at Agios. “With today’s additional TIBSOVO® approval, we are now able to provide a targeted, oral therapy to patients with an IDH1 mutation who may not have other treatment options. In addition, we are continuing our work to expand the utility of TIBSOVO® in newly diagnosed AML patients in ongoing Phase 3 trials in combination with both intensive chemotherapy and azacitidine. I would like to thank the patients, nurses, physicians and caregivers who participated in the clinical trial, as well as the tremendous employees at Agios whose focus on patients made this possible.”
AML is a cancer of the blood and bone marrow marked by rapid disease progression and is the most common acute leukemia affecting adults with approximately 20,000 new cases estimated in the U.S. each year2,3. AML patients are typically older or have comorbidities that preclude the use of intensive chemotherapy4. These patients typically have a worse prognosis and poor outcomes5. The majority of patients with AML eventually relapse6. The five-year survival rate is approximately 28%2. For 6 to 10 percent of AML patients, the mutated IDH1 enzyme blocks normal blood stem cell differentiation, contributing to the genesis of acute leukemia7. IDH1 mutations have been associated with negative prognosis in AML8,9.
“The Phase 1 results for TIBSOVO® demonstrated that this oral, single agent therapy can induce durable responses in newly diagnosed AML patients with an IDH1 mutation,” said Gail J. Roboz, M.D., Professor of Medicine, Director of the Leukemia Program and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine and NewYork-Presbyterian/Weill Cornell Medical Center*. “Many patients included in the study had features associated with particularly aggressive and challenging forms of AML, including secondary disease, adverse risk genetics and prior treatment with hypomethylating agents.”
TIBSOVO® Safety and Efficacy Data1
The efficacy of TIBSOVO® was evaluated in an open-label, single-arm, multicenter clinical trial (Study AG120-C-001, NCT02074839) that included 28 adult patients with newly diagnosed AML with an IDH1 mutation who were assigned to receive a 500 mg daily dose. The cohort included patients who were age 75 or older or had comorbidities that precluded the use of intensive induction chemotherapy (baseline Eastern Cooperative Oncology Group [ECOG] performance status of ≥2, severe cardiac or pulmonary disease, hepatic impairment with bilirubin >1.5 times the upper limit of normal, or creatinine clearance <45 mL/min). Patients had a median age of 77 years (range of 64 to 87) and 68% had AML with myelodysplasia-related changes. The primary endpoint is the combined complete remission (CR) and complete remission with partial hematologic improvement (CRh) rate. CRh is defined as <5% of blasts in the bone marrow, no evidence of disease and partial recovery of peripheral blood counts (platelets >50,000/microliter and ANC >500/microliter).
In this trial, TIBSOVO® demonstrated:
- CR+CRh rate of 42.9% (12 of 28 patients) (95% CI: 24.5, 62.8).
- The CR rate was 28.6% (8 of 28 patients) (95% CI 13.2, 48.7) and the CRh rate was 14.3% (4 of 28 patients) (95% CI 4.0, 32.7).
- Median durations of CR and CR+CRh were not estimable, with 5 patients (41.7%) who achieved CR or CRh remaining on TIBSOVO® treatment (treatment duration range: 20.3 to 40.9 months) as of the data cutoff.
- 58.3% (7 of 12) of patients who achieved CR or CRh were in remission at 1 year after receiving treatment.
- For patients who achieved a CR or CRh, the median time to best response of CR or CRh was 2.8 months (range, 1.9 to 12.9 months).
- Among the 17 patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline, 7 (41.2%) became independent of RBC and platelet transfusions during any 56-day post-baseline period.
- Of the 11 patients who were independent of both RBC and platelet transfusions at baseline, 6 (54.5%) remained transfusion independent during any 56-day post-baseline period.
The safety profile of single-agent TIBSOVO® was evaluated in 28 patients with newly diagnosed AML with an IDH1 mutation treated with a dose of 500 mg daily. The median duration of exposure to TIBSOVO® was 4.3 months (range, 0.3 to 40.9 months). In the clinical trial, 25% (7 of 28) of patients treated with TIBSOVO® experienced differentiation syndrome, which can be fatal if not treated. Of the 7 patients with newly diagnosed AML who experienced differentiation syndrome, 6 (86%) patients recovered. QTc interval prolongation occurred in patients treated with TIBSOVO®. The most common adverse reactions (≥20%) of any grade in patients with newly diagnosed AML were diarrhea, fatigue, decreased appetite, edema, nausea, leukocytosis, arthralgia, abdominal pain, dyspnea, myalgia, constipation, differentiation syndrome, dizziness, electrocardiogram QT prolonged, mucositis and vomiting.
About TIBSOVO® (ivosidenib)
TIBSOVO® is indicated for the treatment of acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test in:
- Adult patients with newly-diagnosed AML who are ≥75 years old or who have comorbidities that preclude use of intensive induction chemotherapy.
- Adult patients with relapsed or refractory AML.
About Agios
Agios is focused on discovering and developing novel investigational medicines to treat cancer and rare genetic diseases through scientific leadership in the field of cellular metabolism and adjacent areas of biology. In addition to an active research and discovery pipeline across both therapeutic areas, Agios has two approved oncology precision medicines and multiple first-in-class investigational therapies in clinical and/or preclinical development. All Agios programs focus on genetically identified patient populations, leveraging our knowledge of metabolism, biology and genomics. For more information, please visit the company’s website at www.agios.com.
*Dr. Roboz has served as a consultant for Celgene, Bayer, Otsuka, Pfizer, Astellas Pharmaceuticals, Argenx, Astex Pharmaceuticals, Hoffman-La Roche, Janssen, Novartis, Amphivena, AbbVie, Sandoz, Eisai, Jazz Pharmaceuticals, Celltrion, Orsenix and Daiichi Sankyo.
References
- TIBSOVO® Prescribing Information (U.S.). Agios Pharmaceuticals, Inc.Cambridge, MA. Revised May/2019.
- National Cancer Institute Surveillance, Epidemiology, and End Results Program. Cancer Stat Facts: Acute Myeloid Leukemia (AML). https://seer.cancer.gov/statfacts/html/amyl.html. Accessed April 2019.
- American Cancer Society. Acute Myeloid Leukemia (AML). https://www.cancer.org/cancer/acute-myeloid-leukemia/about/key-statistics.html. Accessed April 2019.
- Kantarjian H, et al. Intensive chemotherapy does not benefit most older patients (age 70 years or older) with acute myeloid leukemia. Blood. 2010;116(22):4422-4429.
- Dohner H., Estey E., Grimwade D., et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129:424-447.
- Medeiros BC., et al. Big data analysis of treatment patterns and outcomes among elderly acute myeloid leukemia patients in the United States. Ann Hematol. 2015;94:1127-1138.
- DiNardo C. Durable Remissions from Ivosidenib in IDH1-Mutated Relapsed or Refractory AML. New England Journal of Medicine. June 2, 2018
- Zhou KG, Jiang LJ, Shang Z, et al. Potential application of IDH1 and IDH2 mutations as prognostic indicators in non-promyelocytic acute myeloid leukemia: a meta-analysis. Leuk Lymphoma. 2012;53(12):2423-2429.
- Feng J-H, Guo X-P, Chen Y-Y, Wang Z-J, Cheng Y-P, Tang Y-M. Prognostic significance of IDH1 mutations in acute myeloid leukemia: a meta-analysis. Am J Blood Res. 2012;2(4):254-264.
SOURCE: Agios Pharmaceuticals
Post Views: 70
– TIBSOVO® is the First and Only Therapy Approved for Newly Diagnosed AML Patients with an IDH1 Mutation who are Ineligible for Intensive Chemotherapy –
– sNDA Approval Based on 28 Newly Diagnosed Patients from Phase 1 Study of TIBSOVO® in Advanced Hematologic Malignancies with an IDH1 Mutation1 –
– Single Agent TIBSOVO® Demonstrated CR Rate of 28.6% and CR+CRh Rate of 42.9%1 –
CAMBRIDGE, MA, USA I May 02, 2019 I Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases, today announced the U.S. Food and Drug Administration (FDA) approved a supplemental New Drug Application (sNDA) to update the U.S. Prescribing Information for TIBSOVO®, an isocitrate dehydrogenase-1 (IDH1) inhibitor, to include adult patients with newly diagnosed acute myeloid leukemia (AML) with a susceptible IDH1 mutation as detected by an FDA-approved test who are ≥ 75 years old or who have comorbidities that preclude use of intensive induction chemotherapy. The sNDA was granted Priority Review and accepted under the FDA’s Real-Time Oncology Review pilot program, which aims to make the review of oncology drugs more efficient by allowing the FDA access to clinical trial data before the information is formally submitted to the agency. TIBSOVO® received initial FDA approval in July 2018 for adult patients with relapsed or refractory (R/R) AML and an IDH1 mutation1.
“Despite several new AML medicines approved in the last two years, many newly diagnosed patients are still not eligible for existing therapies or combination regimens because of age and other comorbidities,” said Chris Bowden, M.D., chief medical officer at Agios. “With today’s additional TIBSOVO® approval, we are now able to provide a targeted, oral therapy to patients with an IDH1 mutation who may not have other treatment options. In addition, we are continuing our work to expand the utility of TIBSOVO® in newly diagnosed AML patients in ongoing Phase 3 trials in combination with both intensive chemotherapy and azacitidine. I would like to thank the patients, nurses, physicians and caregivers who participated in the clinical trial, as well as the tremendous employees at Agios whose focus on patients made this possible.”
AML is a cancer of the blood and bone marrow marked by rapid disease progression and is the most common acute leukemia affecting adults with approximately 20,000 new cases estimated in the U.S. each year2,3. AML patients are typically older or have comorbidities that preclude the use of intensive chemotherapy4. These patients typically have a worse prognosis and poor outcomes5. The majority of patients with AML eventually relapse6. The five-year survival rate is approximately 28%2. For 6 to 10 percent of AML patients, the mutated IDH1 enzyme blocks normal blood stem cell differentiation, contributing to the genesis of acute leukemia7. IDH1 mutations have been associated with negative prognosis in AML8,9.
“The Phase 1 results for TIBSOVO® demonstrated that this oral, single agent therapy can induce durable responses in newly diagnosed AML patients with an IDH1 mutation,” said Gail J. Roboz, M.D., Professor of Medicine, Director of the Leukemia Program and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine and NewYork-Presbyterian/Weill Cornell Medical Center*. “Many patients included in the study had features associated with particularly aggressive and challenging forms of AML, including secondary disease, adverse risk genetics and prior treatment with hypomethylating agents.”
TIBSOVO® Safety and Efficacy Data1
The efficacy of TIBSOVO® was evaluated in an open-label, single-arm, multicenter clinical trial (Study AG120-C-001, NCT02074839) that included 28 adult patients with newly diagnosed AML with an IDH1 mutation who were assigned to receive a 500 mg daily dose. The cohort included patients who were age 75 or older or had comorbidities that precluded the use of intensive induction chemotherapy (baseline Eastern Cooperative Oncology Group [ECOG] performance status of ≥2, severe cardiac or pulmonary disease, hepatic impairment with bilirubin >1.5 times the upper limit of normal, or creatinine clearance <45 mL/min). Patients had a median age of 77 years (range of 64 to 87) and 68% had AML with myelodysplasia-related changes. The primary endpoint is the combined complete remission (CR) and complete remission with partial hematologic improvement (CRh) rate. CRh is defined as <5% of blasts in the bone marrow, no evidence of disease and partial recovery of peripheral blood counts (platelets >50,000/microliter and ANC >500/microliter).
In this trial, TIBSOVO® demonstrated:
- CR+CRh rate of 42.9% (12 of 28 patients) (95% CI: 24.5, 62.8).
- The CR rate was 28.6% (8 of 28 patients) (95% CI 13.2, 48.7) and the CRh rate was 14.3% (4 of 28 patients) (95% CI 4.0, 32.7).
- Median durations of CR and CR+CRh were not estimable, with 5 patients (41.7%) who achieved CR or CRh remaining on TIBSOVO® treatment (treatment duration range: 20.3 to 40.9 months) as of the data cutoff.
- 58.3% (7 of 12) of patients who achieved CR or CRh were in remission at 1 year after receiving treatment.
- For patients who achieved a CR or CRh, the median time to best response of CR or CRh was 2.8 months (range, 1.9 to 12.9 months).
- Among the 17 patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline, 7 (41.2%) became independent of RBC and platelet transfusions during any 56-day post-baseline period.
- Of the 11 patients who were independent of both RBC and platelet transfusions at baseline, 6 (54.5%) remained transfusion independent during any 56-day post-baseline period.
The safety profile of single-agent TIBSOVO® was evaluated in 28 patients with newly diagnosed AML with an IDH1 mutation treated with a dose of 500 mg daily. The median duration of exposure to TIBSOVO® was 4.3 months (range, 0.3 to 40.9 months). In the clinical trial, 25% (7 of 28) of patients treated with TIBSOVO® experienced differentiation syndrome, which can be fatal if not treated. Of the 7 patients with newly diagnosed AML who experienced differentiation syndrome, 6 (86%) patients recovered. QTc interval prolongation occurred in patients treated with TIBSOVO®. The most common adverse reactions (≥20%) of any grade in patients with newly diagnosed AML were diarrhea, fatigue, decreased appetite, edema, nausea, leukocytosis, arthralgia, abdominal pain, dyspnea, myalgia, constipation, differentiation syndrome, dizziness, electrocardiogram QT prolonged, mucositis and vomiting.
About TIBSOVO® (ivosidenib)
TIBSOVO® is indicated for the treatment of acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test in:
- Adult patients with newly-diagnosed AML who are ≥75 years old or who have comorbidities that preclude use of intensive induction chemotherapy.
- Adult patients with relapsed or refractory AML.
About Agios
Agios is focused on discovering and developing novel investigational medicines to treat cancer and rare genetic diseases through scientific leadership in the field of cellular metabolism and adjacent areas of biology. In addition to an active research and discovery pipeline across both therapeutic areas, Agios has two approved oncology precision medicines and multiple first-in-class investigational therapies in clinical and/or preclinical development. All Agios programs focus on genetically identified patient populations, leveraging our knowledge of metabolism, biology and genomics. For more information, please visit the company’s website at www.agios.com.
*Dr. Roboz has served as a consultant for Celgene, Bayer, Otsuka, Pfizer, Astellas Pharmaceuticals, Argenx, Astex Pharmaceuticals, Hoffman-La Roche, Janssen, Novartis, Amphivena, AbbVie, Sandoz, Eisai, Jazz Pharmaceuticals, Celltrion, Orsenix and Daiichi Sankyo.
References
- TIBSOVO® Prescribing Information (U.S.). Agios Pharmaceuticals, Inc.Cambridge, MA. Revised May/2019.
- National Cancer Institute Surveillance, Epidemiology, and End Results Program. Cancer Stat Facts: Acute Myeloid Leukemia (AML). https://seer.cancer.gov/statfacts/html/amyl.html. Accessed April 2019.
- American Cancer Society. Acute Myeloid Leukemia (AML). https://www.cancer.org/cancer/acute-myeloid-leukemia/about/key-statistics.html. Accessed April 2019.
- Kantarjian H, et al. Intensive chemotherapy does not benefit most older patients (age 70 years or older) with acute myeloid leukemia. Blood. 2010;116(22):4422-4429.
- Dohner H., Estey E., Grimwade D., et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129:424-447.
- Medeiros BC., et al. Big data analysis of treatment patterns and outcomes among elderly acute myeloid leukemia patients in the United States. Ann Hematol. 2015;94:1127-1138.
- DiNardo C. Durable Remissions from Ivosidenib in IDH1-Mutated Relapsed or Refractory AML. New England Journal of Medicine. June 2, 2018
- Zhou KG, Jiang LJ, Shang Z, et al. Potential application of IDH1 and IDH2 mutations as prognostic indicators in non-promyelocytic acute myeloid leukemia: a meta-analysis. Leuk Lymphoma. 2012;53(12):2423-2429.
- Feng J-H, Guo X-P, Chen Y-Y, Wang Z-J, Cheng Y-P, Tang Y-M. Prognostic significance of IDH1 mutations in acute myeloid leukemia: a meta-analysis. Am J Blood Res. 2012;2(4):254-264.
SOURCE: Agios Pharmaceuticals
Post Views: 70
