NEW ORLEANS — Early results with an investigational new agent suggest it may have disease-modifying activity in myelofibrosis, which would be a first in this condition.
The drug, imetelstat (under development by Geron), has a novel mechanism of action of inhibiting telomerase activity in tumor cells, which leads to tumor cell death. This is a rational target for cancer, says the manufacturer, because most cancer cells have a high level of telomerase activity and relatively short telomeres, compared with normal cells.
The new results in myelofibrosis come from 22 patients treated with imetelstat with a follow-up of at least 6 months, and were reported by Ayalew Tefferi, MD, from the Mayo Clinic in Rochester, Minnesota, here at the American Society of Hematology 55th Annual Meeting.
SO Taz, when you say the G has the dough to get the smaller P3 done with no 2ndary, and go fast track, are you counting the 60m they have on hand ?or are you also counting in the extra 50m they just raised at market after the ASH news ? Just curious because you might be right, 0.1 billion $ might be enough to go with an IST P3 and fast track to approval. That would really wreck the status quo,. I like bucking the status quo.
trailblazer Breakthrough therapies can be approved post Phase 2 like what Seattle Genetics did. Geron has enough Capital to run their multi center confirmatory Phase 2 trials that may lead to an early approval. The cost of running an MF trial is much lower than a solid tumor trial.
Four of the 22 patients (18%) had a complete remission, which "has never been seen before with any drug," he said.
As well as complete resolution of symptoms, these 4 patients also showed a complete reversal of bone marrow fibrosis, which is almost unheard of, Dr. Tefferi commented. He showed histology slides from the 4 patients, which showed bone marrow fibrosis before treatment and a complete absence of fibrosis after treatment, so that the bone marrow looked normal.
"These are early results, but they are promising" Dr. Tefferi commented. "Some patients had dramatic responses."
However, one expert not involved with the study said that the responses are in need of qualification.
The bone marrow fibrosis that was reversed was reticulin fibrosis, which is seen in early phases of the disease and is not the striking and severe myelosclerosis and bone marrow scarring that is seen in more advanced disease, said Richard Silver, MD, professor of medicine and director of the Leukemia and Myeloproliferative Center at New York Presbyterian-Weill Cornell Medical Center in New York City. He chaired the session at which these results were presented, and said he found some of the data to be "confounding."
"These were patients in the cellular phase of myelofibrosis," he said. He also noted that 3 of the 4 patients who showed this bone marrow reversal did not have enlarged spleens, so they were relatively early cases, he said. One of the patients had essential thrombocytopenia with a very cellular bone marrow, and was very anemic.
"These are very unusual presenting cases," Dr. Silver commented.
These patients showed clearing of the reticulin bone marrow fibrosis that is seen in earlier stages of myelofibrosis, he continued. This has been seen before with interferon and also with ruxolitinib, but with these drugs, the changes leading to reversal take a long time — several years — to be seen, he said. In contrast, the reversal with imetelstat was seen within 6 months, and as the patients were in the cellular phase of the disease, there is some speculation that the effect seen was some sort of "toxic reaction."