Imetelstat for myelofibrosis
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What is imetelstat for myelofibrosis?
Imetelstat is an experimental infusion therapy currently being tested for myelofibrosis. It’s being evaluated both as a standalone treatment and in combination with Jakafi (ruxolitinib), a widely used oral JAK inhibitor.
In a person with myelofibrosis, the bone marrow overproduces abnormal blood cells. This leads to chronic inflammation and scarring that inhibits the production of healthy, functional blood cells.
Imetelstat works by inhibiting an enzyme called telomerase, which helps keep cells alive by adding more DNA to the ends of chromosomes. Cancer cells generally have more telomerase than normal cells. By blocking the enzyme, imetelstat causes cancer cells to lose this repair mechanism and eventually die off.
While many current myelofibrosis treatments focus on managing daily symptoms, imetelstat aims to go deeper. It may offer a disease-modifying effect by directly killing off the problematic cells in the bone marrow. This therapy is delivered intravenously, traveling through the bloodstream to reach its target.
Developed by Geron, the medication is already approved under the brand name Rytelo for the treatment of other types of blood cancer. Several clinical trials are currently exploring its potential for myelofibrosis. This includes a Phase 3 study for patients with “relapsed” or “refractory” disease — those whose myelofibrosis either returned after initial treatment or failed to respond to it in the first place.
The U.S. has granted imetelstat fast track and orphan drug designations. These regulatory statuses are designed to accelerate the development and review of promising treatments for rare conditions.
Therapy snapshot
| Treatment name | Imetelstat |
| Administration | Intravenous infusion |
| Clinical testing | Currently in Phase 3 testing |
How will imetelstat be administered in myelofibrosis?
Imetelstat is given by intravenous infusion. In a Phase 3 clinical trial testing imetelstat in people with relapsed or refractory myelofibrosis, the medication is being administered once every three weeks, at a dose of 9.4 milligrams per kilogram of body weight (mg/kg).
In an ongoing Phase 1 study testing imetelstat in combination with Jakafi, imetelstat is administered once every four weeks, with various dose levels being evaluated.
Imetelstat in myelofibrosis clinical trials
A Phase 2 clinical trial called IMbark (NCT02426086) assessed the efficacy and safety of imetelstat in people with intermediate-2 or high-risk myelofibrosis who had relapsed after or were refractory to JAK inhibitor therapy. Participants received infusions of imetelstat at a dose of 4.7 mg/kg or 9.4 mg/kg, once every three weeks. The results showed that:
- 10.2% of people in the high dose group and no people in the low dose group achieved at least a 35% reduction in spleen volume after about six months
- about a third of people on the high dose and 6.3% of those on the low dose experienced at least a 50% reduction in overall symptom burden
- those in the high dose group had a median overall survival of about 2.5 years, which is higher than historical averages for this patient group
- the treatment tended to be associated with improvements in disease biomarkers and measures of bone marrow scarring
Imetelstat is now being further tested in two clinical trials:
- The Phase 3 IMpactMF trial (NCT04576156) is comparing the benefits of imetelstat (9.4 mg/kg) with the best available standard of care among people with intermediate-2 or high-risk myelofibrosis whose disease relapsed or was refractory to JAK inhibitor treatment. The study’s main goal is to evaluate imetelstat’s effects on survival.
- The Phase 1 IMproveMF trial (NCT05371964) is evaluating the safety and clinical effects of imetelstat when combined with Jakafi among people with myelofibrosis. It mainly aims to evaluate safety and reductions in symptom burden.
Preliminary data from IMproveMF showed an overall reduction in symptom burden after about six months on the combination regimen, and a trend toward reduced spleen volume.
Imetelstat side effects
In the IMbark trial, where all participants received imetelstat, the most common reported side effects included:
- low blood cell counts
- nausea
- diarrhea
- fatigue
- shortness of breath
- abdominal pain
- general weakness
- fever
- swelling
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