CNS CANCER: Phase I clinical data from patients with low grade glioma receiving vorasidenib or vosidenib confirm early suggestions of efficacy.

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Dec. 2, 2019

SCIENTIFIC

AGIOS Press Release 22/11/19

https://investor.agios.com/news-releases/news-release-details/agios-presents-new-pharmacodynamic-and-response-data-both

Agios Presents New Pharmacodynamic and Response Data from Both Cohorts of the Perioperative Study of Vorasidenib and TIBSOVO® (ivosidenib) in Patients with IDH1 Mutant Positive Low-Grade Glioma.

– Preliminary Efficacy Data Show 31% Overall Response Rate for Both Vorasidenib and TIBSOVO® with Postoperative Treatment –
– Vorasidenib and TIBSOVO® Showed 2-HG Suppression of Greater Than 90% in Resected IDH1 Mutant Gliomas Across All Doses Tested –
– Vorasidenib and TIBSOVO® Demonstrated Favorable Safety Profile at All Doses Tested –
– Registration-enabling Phase 3 INDIGO Study of Vorasidenib in Grade 2 Non-enhancing Glioma with an IDH mutation to Initiate by Year End –

Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases, today presented updated data from the ongoing perioperative study, confirming brain penetrance and robust biomarker suppression with treatment of single agent vorasidenib or TIBSOVO® (ivosidenib) in low-grade glioma with an IDH1 mutation. The data were featured in an oral presentation at the Society for Neuro-Oncology (SNO) Annual Meeting in Phoenix. Vorasidenib, an investigational, oral, selective, inhibitor of the mutant isocitrate dehydrogenase-1 (IDH1) and IDH2 enzymes, was designed for enhanced brain penetrance and selected for pivotal development in IDH mutant low-grade glioma.

Vorasidenib and TIBSOVO® are being evaluated as a single agent in an ongoing perioperative study in IDH1 mutant Grade 2/3 glioma. The primary endpoint is 2-hydroxyglutarate (2-HG) concentration in tumors resected following presurgical treatment with vorasidenib and TIBSOVO® compared with untreated control tumors. Patients were randomized to 500 mg TIBSOVO® once daily, 50 mg vorasidenib once daily or the control arm in cohort 1; and 250 mg TIBSOVO® twice daily or 10 mg vorasidenib once daily in cohort 2. Patients were treated for four weeks prior to surgery and had the option to continue postoperative treatment until disease progression.

As of the July 26, 2019 data cutoff, 49 patients were randomized before surgery, and 39 remain on treatment. The median (range) postoperative treatment duration for all doses was 5.42 (0.9–13.5) months for vorasidenib and 6.93 (1.0–13.2) months for TIBSOVO®. Baseline characteristics were similar across the control and treated groups. Overall, 88% of patients had World Health Organization (WHO) classified Grade 2 tumors. Less than a third of patients had prior radiation therapy and approximately half had prior systemic therapy.

Data from the 42 efficacy evaluable patients (21 in the vorasidenib arm; 21 in the TIBSOVO® arm) as of the data cut-off showed:

Among patients treated post-operatively with 50 mg vorasidenib, four patients (31%) achieved objective tumor responses (two achieved a partial response, defined as tumor shrinkage based on T2/FLAIR signal of at least 50%, and two achieved a minor response, defined as tumor shrinkage based on T2/FLAIR signal of at least 25% but less than 50%) according to the investigator by Response Assessment in Neuro-Oncology for low-grade glioma (RANO-LGG).

Among patients treated post-operatively with 500 mg TIBSOVO®, four patients (31%) achieved confirmed responses (two achieved a partial response and two achieved a minor response) according to the investigator by RANO-LGG.

15 patients treated with vorasidenib and 16 patients treated with TIBSOVO® experienced stable disease, resulting in disease control rates of 90% and 95% respectively.