Agios Pharmaceuticals may be one step closer to finding a breakthrough approach to treat cancer in a more personalized fashion.
The Cambridge, MA-based company's small-molecule mutant-specific inhibitors have yielded promising results in preclinical studies of primary human tumor models. Two studies published in the journal Science by Agios scientists last week, plus a third study by a separate team of scientists published in Science the week before, add to growing evidence that the metabolic enzymes from mutated isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) genes could be potential new targets to treat cancer.
In a variety of blood and solid tumors, these IDHI and IDH2 genes are altered and produce metabolites that drive cancer growth. The mutations are found in about a quarter of adult cases of acute myeloid leukemia, more than 70% of patients with brain cancer known as glioma and about one in 5 cases of bile duct cancer.
"We're extremely excited because we've shown for the first time that in human cancers that we can see a therapeutic effect by inhibiting IDH," Agios Chief Scientific Officer Scott Biller said to FierceBiotechResearch.
The first research paper details how Agios developed its mutant-selective IDH2 inhibitor. First, scientists took cells from acute myeloid leukemia patients with the IDH2 mutation. Then using the inhibitor, scientists observed differentiation of leukemic cells. In the second article, Agios researchers report that a selective mutant IDH1 inhibitor discovered by the company blocked the ability of mutant IDH1 to produce 2-HG--a metabolite that appears in high levels in tumors with IDH mutations--in an in vivo primary xenograft model. The inhibitor stopped the growth of IDH1-mutant glioma cells that were taken from the patient.
Agios' director of biology, Katharine Yen, told FierceBiotechResearch that the compounds they developed are different from existing cancer treatments because they are targeted therapies. In other words, the Agios compounds would treat specific patients with the IDH1 and IDH2 mutations, avoiding the need for harmful chemotherapy treatments--the current standard of care for leukemia and glioma patients.
Just last week, Agios announced a partnership with Foundation Medicine to find patients with the genetic profiles most suited to treatment with therapies involving these two cancer metabolism targets.
Biller said he's confident clinical trials will begin in 12 to 24 months.
- here's the press release
- get the abstracts of the Agios researchers' work (paper 1 and paper 2)
- and the third abstract