– TIBSOVO® Reduced the Risk of Disease Progression or Death by 63% (HR=0.37, p<0.001); Median PFS for Patients Randomized to TIBSOVO® was 2.7 months Compared to 1.4 Months with Placebo –

– TIBSOVO® Patients Had 6-month PFS Rate of 32% and 12-month PFS Rate of 22%; No Placebo Patients Were Free From Progression for More Than Six Months –

– Supplemental New Drug Application on Track for Submission by End of 2019 –

BARCELONA, Spain I September 30, 2019 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 the global Phase 3 ClarIDHy trial of TIBSOVO® (ivosidenib) in previously treated cholangiocarcinoma patients with an isocitrate dehydrogenase 1 (IDH1) mutation in a Presidential Symposium at the European Society for Medical Oncology Congress (ESMO). Results from the ClarIDHy trial demonstrated a statistically significant improvement in progression-free survival (PFS) by independent radiology review of 2.7 months among patients randomized to TIBSOVO® compared with 1.4 months among placebo patients (hazard ratio [HR] 0.37; 95% CI [0.25, 0.54], p<0.001). The safety profile observed in the study was consistent with previously published data.

“Advanced cholangiocarcinoma is an aggressive disease oftentimes characterized by rapid progression following multiple lines of therapy, and there are no currently approved treatments,” said Ghassan Abou-Alfa, M.D., medical oncologist at Memorial Sloan Kettering Cancer Center, who presented the data at ESMO. “The ClarIDHy study is the first randomized trial in previously treated IDH1 mutant cholangiocarcinoma patients and demonstrates that TIBSOVO® provides significant improvement in PFS compared to placebo, while also showing a favorable trend in overall survival. These critical data also provide strong justification for genomic testing in cholangiocarcinoma patients where a targeted therapeutic approach may provide benefit.”

“Since we began clinical trials of TIBSOVO® in solid tumors five years ago, we have hoped to provide benefit to cholangiocarcinoma patients who desperately need new treatment options. The results of the ClarIDHy trial help to establish the role that this targeted therapy may play in the treatment paradigm for patients with an IDH1 mutation,” said Chris Bowden, M.D., chief medical officer at Agios. “Moving forward, we’re focused on submitting our supplemental new drug application for previously treated IDH1 mutant cholangiocarcinoma patients by the end of the year.”

ClarIDHy Phase 3 Trial
The ClarIDHy trial is a global, randomized Phase 3 trial in previously treated IDH1 mutant cholangiocarcinoma patients who have documented disease progression following one or two systemic therapies in the advanced setting. Patients were randomized 2:1 to receive either single-agent TIBSOVO® 500 mg once daily or placebo with crossover to TIBSOVO® permitted at the time of documented radiographic progression per RECIST 1.1. As of the January 31, 2019 data cutoff, 185 patients were randomized, with 124 patients in the TIBSOVO® arm and 61 patients in the placebo arm. Thirty-five patients randomized to placebo (57.4%) crossed over to open-label TIBSOVO® upon radiographic disease progression and unblinding.

Efficacy Results
Efficacy data as of the data cut-off showed:

  • Median progression-free survival (PFS) for patients randomized to TIBSOVO® was 2.7 months compared to 1.4 months with placebo (hazard ratio [HR]=0.37; 95% CI [0.25, 0.54], p<0.001) as assessed by independent radiology review. PFS benefits were observed across all subgroups analyzed.
  • The estimated PFS rate was 32% at six months and 22% at 12 months for patients randomized to TIBSOVO®, while no patients randomized to placebo were free from progression beyond these timepoints as of the data cut-off.
  • In the TIBSOVO® arm, 2% of patients achieved a partial response and 51% had stable disease, compared to 28% with stable disease in the placebo arm.
  • Median overall survival (OS) based on 78 events was 10.8 months for patients randomized to TIBSOVO® compared to 9.7 months for placebo patients (HR=0.69; 95% CI [0.44, 1.10], p=0.06). Using the rank-preserving structural failure time (RPSFT) method to reconstruct the survival curve for the placebo subjects as if they never crossed over to TIBSOVO®, the median OS with placebo adjusts to 6 months (HR=0.46; 95% CI [0.28, 0.75], p<0.001).

Safety Results
A safety analysis conducted for all patients as of the data cut-off demonstrated:

  • Less than half of patients experienced a Grade 3 or above treatment-emergent adverse event (TEAE) in either arm (46.2% with total TIBSOVO® [includes patients who crossed over from placebo to TIBSOVO®] vs. 35.6% on placebo), with the most common being ascites (7.7% total TIBSOVO® vs. 6.8% placebo).
  • TEAEs leading to discontinuation were more common with placebo compared with total TIBSOVO® (8.5% vs. 5.8%).
  • TEAEs leading to dose reductions (2.6% vs. 0%) and interruptions (26.3% vs. 16.9%) were more common with total TIBSOVO® relative to placebo.
  • The most common TEAEs of any grade for total TIBSOVO® were nausea (32%), diarrhea (29%) and fatigue (24%).

TIBSOVO® is not approved in any country for the treatment of patients with advanced cholangiocarcinoma.

Conference Call Information
Agios will host a conference call and live webcast with presentation slides today at 1 p.m. ET /7 p.m. CET to discuss the data from the ClarIDHy study. To participate in the conference call, please dial 1-877-377-7098 (domestic) or 1-631-291-4547 (international) and refer to conference ID 5209309. The live webcast can be accessed under “Events & Presentations” in the Investors section of the company’s website at www.agios.com. The archived webcast will be available on the company’s website beginning approximately two hours after the event.

About Cholangiocarcinoma
Cholangiocarcinoma (CC) is a rare cancer of the bile ducts within and outside of the liver. Cases that occur within the liver are known as intrahepatic cholangiocarcinoma (IHCC) and those that occur outside the liver are considered extrahepatic. Mutations in IDH1 occur in up to 20% of IHCC cases. Current treatment options for localized disease include surgery, radiation and/or other ablative treatments. There are no approved systemic therapies for cholangiocarcinoma and limited chemotherapy options are available in the advanced setting. Gemcitabine-based chemotherapy is often recommended for newly diagnosed advanced or metastatic disease.

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.

SOURCE: Agios