VIENNA, Austria (TheStreet) -- Two experimental drugs from Agios Pharmaceuticals (AGIO) designed to curb the overactive metabolism of certain kinds of mutated blood cancer cells are showing prolonged responses not normally seen in patients with advanced disease, according to new study results announced Friday.
For one of the Agios drugs, known as AG-221, more than three-quarters of responding blood cancer patients have remained on treatment for six months or longer, with the longest treatment lasting 15 months.
"This is a very high-risk patient population with life expectancy measured in weeks or just a few months, so to see this response and the duration of response is, to some extent, unheard of," said Dr. Eytan Stein of New York's Memorial Sloan Kettering Cancer Center and an investigator involved in the Agios clinical trials.
Updated results from two, phase I studies of Agios drugs AG-221 and AG-120 are being presented at a meeting of the European Hematology Association underway in Vienna.
Celgene (CELG) is partnered with Agios on the development and marketing of AG-221 and AG-120, if approved. A phase III study of AG-221 will start in the second half of this year. Meanwhile, the phase III study of AG-120 is expected to begin in the first half of 2016.
Both AG-221 and AG-120 are pills designed to block mutated, metabolic enzymes known as IDH2 and IDH1, respectively. Normally, cells use the IDH enzymes to help break down nutrients and generate energy. When mutated, the IDH enzymes alter the genetic programming of cells, preventing them from maturing and allowing them to grow uncontrollably.
Patients with certain types of blood cancer have bone marrow crowded with undifferentiated, rapidly dividing blast cells. AG-221 and AG-120 block the mutated IDH enzymes and allow the leukemic cells in bone marrow to mature into normal blood cells. Agios estimates that between 18% to 24% of certain types of leukemia contain mutated IDH enzymes.
In an update to a phase I study encompassing 158 evaluable patients with advanced blood cancers containing IDH2 mutations, treatment with escalating doses of AG-221 demonstrated an overall response rate of 40%. [The study has actually enrolled 177 patients to date, but some aren't treated long enough to evaluate for response.]
Of the 63 responding patients, 26 patients, or 17%, achieved a complete remission, meaning there was no evidence of leukemic cells in their bone marrow. Another 19 patients showed near complete remissions. Eighteen patients had partial remissions following AG-221 treatment.
The 40% overall response rate to AG-221 reported Friday is lower than the 56% overall response rate announced last December when fewer patients were enrolled. The 17% complete response rate increased from 13% previously, however.
Seventy-six percent of the 63 patients responding to AG-221 remain on treatment for six months or longer. Nine of the 63 responding patients eventually relapsed or died while on therapy.
A majority of the patients enrolled in the phase I study have acute myelogenous leukemia (AML) that is no longer responsive to multiple lines of previous therapies. Among these patients with very advanced disease, the overall response and complete response rates were 41% and 18%, respectively.
A smaller group of 22 patients with AML not previously treated were also administered AG-221. There were seven patients, or 32%, who achieved some objective response, including three complete responders. There are too few of these previously untreated AML patients followed for too short a time to draw conclusions about the lower response rate to AG-221, said Sloan Kettering's Stein.
Half of another 14 patients with relapsed, refractory myelodysplastic syndrome (MDS) also responded to treatment with AG-221, including two complete responders.
Separately, Agios is also reporting Friday updated results from a phase I study of AG-120 in patients with advanced blood cancers containing the IDH1 enzyme mutation.
Among 52 evaluable patients, the overall response rate to AG-120 was 31%, including a complete remission rate of 15%. With shorter follow up, 79% of responding patients remain on treatment for at least three months. Some patients remain on AG-120 treatment for up to 11 months. In a previous update to the phase I study reported last November with fewer evaluable patients, the overall response rate to AG-120 was 50%.
Both AG-221 and AG-120 were generally well tolerated. Thirty-five serious adverse events were reported with AG-120, including four cases of abnormally high white blood cell counts related to the drug. Thirteen patients in the AG-120 study have died to date, all due to disease progression or unrelated to the drug. In the AG-221 study, serious adverse events related to the drug were reported in 27 patients.
Looking ahead, Agios is expanding the phase I studies of AG-221 and AG-120, in addition to planning the phase III studies.
Most notably, another 125 patients with IDH2-mutant positive AML who are in second or later relapse will be enrolled and treated with AG-221. There is no approved treatment option for these patients, so the results, if positive, could form the basis for an accelerated approval filing.
Agios CEO David Schenkein demurred when asked about specific regulatory timelines for AG-221, except to say he "wouldn't rule out the possibility" of an accelerated approval filing strategy.