Agios Announces Updated Data from Phase 1 Study of Ivosidenib or Enasidenib in Combination with Standard Induction and Consolidation Chemotherapy in Newly Diagnosed AML Patients With an IDH Mutation

– 91% CR+CRi/CRp Rate in Ivosidenib-treated Patients with De Novo AML and 53% in Ivosidenib-treated Patients with Secondary AML –

– 77% CR+CRi/CRp Rate in Enasidenib-treated Patients with De Novo AML and 64% in Enasidenib-treated Patients with Secondary AML

– Randomized Phase 3 Combination Trial, HOVON 150 AML/AMLSG 29-18, in Newly Diagnosed IDHm AML Patients Eligible for Intensive Chemotherapy Planned to Initiate by Year-End 2018 –

SAN DIEGO, CA, USA I December 03, 2018 I Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases, today presented data from a Phase 1 study evaluating ivosidenib or enasidenib in combination with standard induction and consolidation chemotherapy in patients with newly diagnosed acute myeloid leukemia (AML) and an isocitrate dehydrogenase (IDH)1 or IDH2 mutation. The data were featured in an oral presentation at the 60th American Society of Hematology Annual Meeting in San Diego.

“These data demonstrate that combining full doses of standard induction and consolidation chemotherapy with ivosidenib or enasidenib is well tolerated and has the potential to provide benefit for AML patients in the frontline setting,” said Eytan Stein, M.D., study investigator and attending physician in the leukemia service at Memorial Sloan Kettering Cancer Center. “The addition of an IDH inhibitor to induction and consolidation followed administration as single-agent maintenance therapy for patients with newly diagnosed AML will be evaluated further in a Phase 3 randomized study.”

“The molecular remissions observed in these newly diagnosed AML patients is encouraging,” said Chris Bowden, M.D., chief medical officer at Agios. “In conjunction with Celgene, we will provide support of the Phase 3 HOVON 150 AML/AMLSG 29-18 study, which is planned to initiate by year-end. HOVON 150 AML/AMLSG 29-18 is an intergroup sponsored, global, registration-enabling trial combining ivosidenib or enasidenib with standard induction and consolidation chemotherapy followed by a maintenance therapy period in frontline AML patients with an IDH1 or IDH2 mutation, respectively.”

About the Ongoing Phase 1 Study
As of the August 1, 2018 data cut-off, 60 newly diagnosed AML patients with mIDH1 received 500 mg of ivosidenib and standard induction chemotherapy (daunorubicin 60 mg/m2/day or idarubicin 12 mg/m2/day x 3 days with cytarabine 200 mg/m2/day x 7 days) and 93 newly diagnosed AML patients with mIDH2 received 100 mg of enasidenib and standard induction chemotherapy. After induction, patients received up to four cycles of consolidation chemotherapy while continuing ivosidenib (n=28) or enasidenib (n=45). Patients who achieved a complete response (CR) or a complete response with incomplete neutrophil or platelet recovery (CRi/CRp) after consolidation could continue taking single agent ivosidenib or enasidenib daily until the end of the study which is up to two years from the last patient dosed.

  • 70% of ivosidenib-treated patients and 63% of enasidenib-treated patients had de novo AML, while the remaining had secondary AML (sAML).
  • In patients with sAML, 22% in the ivosidenib cohort and 50% in the enasidenib cohort had received prior hypomethylating agent therapy.
  • The median age of patients was 62.5 years (range 24-76) in the ivosidenib cohort and 63 years (range 27-77) in the enasidenib cohort.
  • The most commonly occurring baseline co-mutations in ivosidenib-treated patients were DNMT3A, NPM1, ASXL1 and BCOR while in enasidenib-treated patients, the most commonly occurring baseline mutations were DNMT3A, SRSF2, ASXL1 and RUNX1.

Ivosidenib Results

Safety Data

  • The frequency of Grade 3 or higher adverse events of interest, regardless of attribution, during the induction period were: IDH differentiation syndrome in 3% (2/60) of patients, QT interval prolongation in 2% (1/60) of patients and blood bilirubin increased in 7% (4/60) of patients.
  • The 30-day mortality rate was 5% and the 60-day mortality rate was 8%.

Efficacy Data

  • An overall best response of CR+CRi/CRp was achieved in 80% (39/49) of efficacy evaluable patients.
  • The CR+CRi/CRp rate for de novo patients was 91% (31/34) and 53% (8/15) for sAML patients.
  • In a subset of patients who achieved a CR or CRi/CRp, elimination of measurable residual disease (MRD) by flow cytometry was observed in 88% (15/17) of patients.
  • In patients whose best response was CR or CRi/CRp, IDH1 mutation clearance by digital PCR was achieved in 41% (12/29) of patients.
  • At the time of the data cut-off, the probability of survival at one-year was 79% and median overall survival (OS) was not yet estimable.
  • The median time to absolute neutrophil count (ANC) recovery (>500/µL) from induction therapy (n=38) was 28 days (95% CI 28, 30). Median time to platelet recovery (>50,000/µL) from induction therapy (n=38) was 28 days (95% CI 27, 30).

Enasidenib Results

Safety Data

  • The frequency of Grade 3 or higher adverse events of interest, regardless of attribution, during the induction period were: IDH differentiation syndrome in 1% (1/93) of patients and blood bilirubin increased in 14% (13/93) of patients.
  • The 30-day mortality rate was 5% and the 60-day mortality rate was 9%.

Efficacy Data

  • An overall best response of CR+CRi/CRp was achieved in 72% (64/89) of efficacy evaluable patients.
  • The CR+CRi/CRp rate for de novo patients was 77% (43/56) and 64% (21/33) for sAML patients.
  • In a subset of patients who achieved a CR or CRi/CRp, elimination of MRD by flow cytometry was observed in 45% (9/20) of patients.
  • In patients whose best response was CR or CRi/CRp, IDH2 mutation clearance by digital PCR was achieved in 25% (15/59) of patients.
  • At the time of the data cut-off, the probability of survival at one-year was 75% and median OS was not yet estimable.
  • The median time to ANC recovery (>500/µL) from induction therapy (n=46) was 34 days (95% CI 31, 36). Median time to platelet recovery (>50,000/µL) from induction therapy (n=46) was 30 days (95% CI 29, 34).

Neither IDHIFA® nor TIBSOVO® are approved for the treatment of patients with newly diagnosed AML or approved in combination with induction and consolidation chemotherapy.

About TIBSOVO® (ivosidenib)

TIBSOVO® (ivosidenib) is an isocitrate dehydrogenase-1 (IDH1) inhibitor indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible IDH1 mutation as detected by an FDA-approved test. For more information, visit TIBSOVO.com.

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. 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.

About Agios/Celgene Collaboration
IDHIFA® (enasidenib) is part of Agios' collaboration with Celgene Corporation. Under the terms of the 2010 collaboration agreement focused on cancer metabolism, Celgene has worldwide development and commercialization rights for IDHIFA® (enasidenib). Agios continues to conduct certain clinical development activities within the IDHIFA® (enasidenib) development program and is eligible to receive reimbursement for those development activities and up to $80 million in remaining payments assuming achievement of certain milestones, and royalties on any net sales. Celgene and Agios are currently co-commercializing IDHIFA® (enasidenib) in the U.S. Celgene will reimburse Agios for costs incurred for its co-commercialization efforts.

SOURCE: Agios

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