- Safety Profile Confirmed; Signs of Clinical and Biological Activity Observed; Recommended Phase 2 Dose Selected -
- Phase 1 Expansion Cohorts for Patients with IDH1 Mutant Positive Glioma, Cholangiocarcinoma, Chondrosarcoma and Other Advanced Solid Tumors Are Open and Enrolling -
- Randomized Phase 2 Study of AG-120 in Cholangiocarcinoma Planned for 2016 -
- Company to Host Investor Event and Webcast Today -
"Glioma, cholangiocarcinoma and chondrosarcomas are all extremely difficult-to-treat diseases with limited therapeutic options," said
"We are excited to present the first data from AG-120 in solid tumors as we explore the novel mechanism of action of our IDH inhibitors in these indications," said
This ongoing Phase 1 trial is assessing the safety and tolerability of AG-120 in advanced solid tumors, including glioma, intrahepatic cholangiocarcinoma (IHCC) and chondrosarcomas that harbor an IDH1 mutation in a dose-escalation phase followed by an expansion phase. As of
The safety analysis conducted for all 62 treated patients as of
- No dose limiting toxicities have been observed.
- The majority of adverse events reported by investigators were mild to moderate, with the most common being nausea, diarrhea, vomiting, anemia and QT prolongation.
- The majority of serious adverse events (SAE) were disease-related.
- A maximum tolerated dose (MTD) has not been reached.
Agios also analyzed efficacy data from 55 response-evaluable patients as of
- Treatment with AG-120 showed substantial reduction of the oncometabolite 2-hydroxglutarate (2HG) in plasma and tumor tissue.
- Imaging (magnetic resonance spectroscopy) results suggest that AG-120 can lower 2HG in the brain.
- Chondrosarcoma: Seven of the 11 patients with IDH1 mutant positive chondrosarcoma had stable disease. Five of these patients maintained stable disease for six months or more. The six-month clinical benefit response rate was 5/9 or 56 percent.
- IHCC: One out of 20 patients with IDH1 mutant positive IHCC had a partial response (PR) and 11 patients had stable disease. Six of these patients, including one with a PR and five with stable disease, maintained their response for six months or more. The six-month clinical benefit response rate was 6/14 or 43 percent.
- Glioma: Ten out of 20 patients with IDH1 mutant positive glioma had stable disease. Four of these patients maintained stable disease for six months or more. The six-month clinical benefit response rate was 4/16 or 25 percent.
- Other: One of the four patients with other IDH1 mutant positive solid tumors had stable disease.
Next Steps for AG-120 in Solid Tumors
Currently enrolling four expansion cohorts of 25 patients each, who receive the recommended dose of 500 mg of AG-120 once daily, with:
- Low grade glioma with ≥ six months of prior scans to assess volumetric changes
- Second-line cholangiocarcinoma
- High grade (metastatic) chondrosarcoma
- Other solid tumors with an IDH1 mutation
- Initiate a randomized Phase 2 study of AG-120 in cholangiocarcinoma in 2016.
Investor Event and Webcast Information
Agios will host an investor event with Dr.
Chondrosarcoma is a heterogeneous group of cancers that arise from cartilage in the bone and joint. It is the most common type of bone cancer with 700-1,000 people diagnosed per year in the U.S. IDH1/2 mutations occur in 40-50 percent of central chondrosarcomas. The prognosis is based on disease burden – for localized disease, there is curative potential with surgery, but metastatic disease has a low five-year survival rate. Radiation is not effective, and chemotherapy is of limited benefit and primarily used to convert non-resectable cancer to resectable. Treatment for metastatic disease is mainly palliative.
About Intrahepatic Cholangiocarcinoma (IHCC)
IHCC occurs within the liver, and the prognosis is worse than for other biliary tract tumors. The incidence of IHCC is increasing due to cirrhosis, alcoholic liver disease and hepatitis C. IHCC has a poor five-year survival rate, with 15-30 percent for local disease and 2 percent for metastatic disease. IDH1/2 mutations are present in approximately 25 percent of IHCCs. Surgery is the only chance for curing localized disease. Surgery, radiation and chemotherapy are palliative for metastatic disease.
Glioma presents in varying degrees of tumor aggressiveness, ranging from slower growing (low grade glioma) to rapidly progressing (high grade glioma). Common symptoms include memory disturbance, sensory impairment neurologic deficits and seizures. The long-term prognosis is poor with a five-year survival rate of 33 percent. Median survival is 12-15 months for glioblastoma and 2-5 years for anaplastic glioma. IDH1 mutations are highly prevalent.
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.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding the potential benefits of Agios' product candidates targeting IDH mutations, including AG-120; its plans for the clinical development of AG-120; its plans regarding future data presentations; and the benefit of its strategic plans and focus. The words "anticipate," "believe," "estimate," "expect," "intend," "may," "plan," "predict," "project," "potential," "hope," "could," "would" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from Agios' current expectations and beliefs. For example, there can be no guarantee that any product candidate Agios is developing will successfully commence or complete necessary preclinical and clinical development phases, or that development of any of Agios' product candidates will successfully continue. There can be no guarantee that any positive developments in Agios' business will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other important factors, including: Agios' results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the U.S.
Renee Leck, Senior Manager, Investor Relations and Public Relations [email protected] 617-649-8299