On December 5, 2015 Agios Pharmaceuticals, Inc. (Nasdaq:AGIO), a leader in the fields of cancer metabolism and rare genetic metabolic disorders, reported new data from the ongoing Phase 1 study evaluating single agent AG-120, a first-in-class, oral, selective, potent inhibitor of mutant isocitrate dehydrogenase-1 (IDH1), in advanced hematologic malignancies (Press release, Agios Pharmaceuticals, DEC 5, 2015, View Source [SID:1234508406]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The data are being presented at the 2015 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (ASH) (Free ASH Whitepaper) taking place December 5-8, 2015 in Orlando. AG-120 is being developed in collaboration with Celgene.

Data as of October 1, 2015 from 87 patients with advanced IDH1 mutant positive hematologic malignancies confirmed a favorable safety profile consistent with previously reported data and showed durable clinical activity in 78 dose-escalation patients. Twenty-nine patients remain on study as of the analysis. Efficacy data is provided from the dose-escalation phase of the study only, where an overall response rate of 35 percent (27 of 78 response-evaluable patients) and a complete remission rate of 15 percent (12 of 78 response-evaluable patients) were observed. Patients were on study treatment for up to 14.1 months with a median duration of treatment of 2.9 months (ranging from 0.1 to 14.1 months). Data continue to show durable clinical activity for AG-120, with responses maintained for up to 12.5 months and a median duration of response of 5.6 months (previously unreported).

"With the addition of 30 new patients to the study, AG-120 has maintained durable responses and continues to demonstrate an impressive single-agent overall response rate of 35 percent," said Courtney DiNardo, M.D., lead investigator and assistant professor, department of leukemia at the University of Texas MD Anderson Cancer Center. "These data further validate AG-120’s potential to provide clinical benefit for IDH1 mutant relapsed/refractory AML patients with few, if any effective therapeutic options."

"These data increase our confidence in the favorable safety and efficacy profile of AG-120," said Chris Bowden, M.D., chief medical officer of Agios. "Our focus remains on bringing AG-120 to patients with IDH1 mutant cancers as quickly as possible, and we look forward to continuing to enroll our 125-patient expansion arm in relapsed/refractory AML and initiating two frontline studies to reach additional IDH1 mutant AML patients in need of better options."

About the Ongoing Phase 1 Trial for AG-120 in Advanced Hematologic Malignancies

AG-120 is being evaluated in an ongoing Phase 1 trial that includes a dose escalation phase and four expansion cohorts, including:

Arm 1: 125 IDH1 mutant positive AML patients who relapsed after bone marrow transplantation, are in second or later relapse, refractory to second line induction or reinduction treatment

Arm 2: 25 untreated IDH1 mutant positive AML patients who are not candidates for standard-of-care chemotherapy

Arm 3: 25 patients with other non-AML IDH1 mutant, relapsed or refractory advanced hematologic malignancies

Arm 4: 25 patients with relapsed IDH1 mutant positive AML not eligible for arm 1 or standard of care

Data reported are from patients treated with AG-120 administered from 200 mg to 1,200 mg total daily doses as of October 1, 2015. The median age of these patients is 68 (ranging from 36-89). Patients received a median of two prior lines of therapy (ranging from zero to five). A safety analysis was conducted for all 87 treated patients and an efficacy analysis was conducted in the evaluable population of 78 dose-escalation patients, which includes all patients with a pre-AG-120 screening assessment and day 28 or later response assessment or an earlier discontinuation for any reason.

Safety Data

Of the 87 treated patients, 78 were from the dose-escalation phase and nine from the expansion.

The majority of adverse events reported by investigators were mild to moderate, with the most common being fatigue, diarrhea, pyrexia and nausea.
51 patients experienced at least one serious adverse event (SAE), the majority being disease related.
A maximum tolerated dose (MTD) has not been reached.
19 patients discontinued from the study due to death, and all were considered unrelated to AG-120.
All cause mortality at 30 and 60 days was 10.3 percent and 18.4 percent, respectively.

Efficacy Data

Twenty-seven out of 78 response-evaluable patients from the dose-escalation achieved investigator-assessed objective responses for an overall response rate of 35 percent.

Of the 27 patients who achieved an objective response, there were 12 complete remissions (CR), seven CRs with incomplete platelet recovery (CRp), six marrow CRs (mCR), one CR with incomplete hematologic recovery (CRi) and one partial remission (PR).
Patients were on study treatment for up to 14.1 months with a median duration of treatment of 2.9 months (ranging from 0.1 to 14.1 months).

Data continue to show durable clinical activity for AG-120, with responses maintained for up to 12.5 months and a median duration of response of 5.6 months.

2015 Milestones for AG-120 in Hematologic Malignancies

Remaining milestones for AG-120 in 2015 include:

Continue to enroll patients in the expansion cohort of 125 patients with IDH1 mutant positive AML who relapsed after bone marrow transplantation, are in second or later relapse, refractory to second line induction or reinduction treatment.
Initiate a Phase 1b combination study of either AG-221 or AG-120 with standard induction (7+3, Ara-C and idarubicin/daunorubicin) and consolidation (Ara-C, or mitoxantrone with etoposide) chemotherapy in newly diagnosed AML patients eligible for intensive chemotherapy by the end of 2015.

Investor Event and Webcast Information

Agios will host an investor event on Monday, December 7, 2015 beginning at 12:00 p.m. ET in Orlando to review data presented at ASH (Free ASH Whitepaper), including new data from the ongoing studies of AG-221 and AG-120. The event will be webcast live and can be accessed under "Events & Presentations" in the Investors and Media section of the company’s website at www.agios.com.

About IDH Mutations and Cancer

IDH1 and IDH2 are two metabolic enzymes that are mutated in a wide range of hematologic and solid tumor malignancies. Normally, IDH enzymes help to break down nutrients and generate energy for cells. When mutated, IDH increases production of an oncometabolite 2-hydroxyglutarate (2HG) that alters the cells’ epigenetic programming, thereby promoting cancer. 2HG has been found to be elevated in several tumor types. Agios believes that inhibition of the mutated IDH proteins may lead to clinical benefit for the subset of cancer patients whose tumors carry them.

About Acute Myelogenous Leukemia (AML)

AML, a cancer of blood and bone marrow characterized by rapid disease progression, is the most common acute leukemia affecting adults. Undifferentiated blast cells proliferate in the bone marrow rather than mature into normal blood cells. AML incidence significantly increases with age, and according to the American Cancer Society, the median age of onset is 66. Less than 10 percent of U.S. AML patients are eligible for bone marrow transplant and the vast majority of patients do not respond to chemotherapy and progress to relapsed/refractory AML. The five-year survival rate for AML is approximately 20 to 25 percent. IDH1 and IDH2 mutations are present in about 15 to 23 percent of AML cases.