Novel Drug Decreases Fibrosis in Myelofibrosis, A Type of Blood Cancer

Treatment with the novel drug GB2064 was associated with decreased fibrosis in patients with myelofibrosis, a type of blood cancer, according to findings from an ongoing phase 2 trial.

An intermediate assessment of the ongoing phase 2a MYLOX-1 trial showed that the novel drug GB2064 decreased bone marrow fibrosis in patients with myelofibrosis, a type of cancer in the bone marrow.

Myelofibrosis is the result of the bone marrow producing too much scar tissue — a process called fibrosis — which results in the improper and decreased production of blood cells. Reducing fibrosis is pivotal in slowing the progression of myelofibrosis.

Findings from the MYLOX-1 trial showed four out of the five patients with myelofibrosis who were able to be evaluated had a grade 1 or higher reduction in collagen fibrosis in the bone marrow. Of note, the extent of bone marrow fibrosis is based a four-level grading system. Past research has demonstrated that a higher bone marrow fibrosis score is a predictor of poor survival.

The four patients who experienced a minimum reduction of one grade in bone marrow fibrosis had stable hemoglobin, white blood cell count and thrombocytes, as well as stable spleen volume over the six months of treatment.

A stable spleen volume is often of interest in patients with myelofibrosis because the blood cancer often causes a person to have an enlarged spleen. This side effect is commonly referred to as debilitating and can be associated with significant abdominal pain and decreased physical activity.

GB2064 works by inhibiting LOXL2, a protein that plays a role in the modification of type 1 collagen as well as cancer cells.

“It is wholly unprecedented and very encouraging to observe a reduction in collagen fibrosis in this patient population. It is exciting to see the first clinical validation of LOXL2 as a fibrosis target,” Dr. Srdan Verstovsek, the primary investigator in the MYLOX-1 trial and a professor in the Department of Leukemia in the Division of Cancer Medicine at the University of Texas MD Anderson Cancer Center in Houston, said in a press release.

Sixteen patients received GB2064 in the MYLOX-1 trial — eight are still on treatment, while eight have stopped, due to either side effects or disease progression. Side effects were commonly gastrointestinal-related and manageable with standard therapy.

For the five patients who completed six months or more of treatment with GB2064, there were no serious side effects reported. The only event that was possibly related to the drug was a fall.

The MYLOX-1 trial is still recruiting new participants. To be eligible, patients must have progressive myelofibrosis and be ineligible or refractory or intolerant to an available JAK inhibitor.

Researchers expect to complete the trial in December 2022.

“It is exciting and encouraging to see a clear reduction in collagen fibrosis following the administration of a selective LOXL2 inhibitor in four of the five evaluable patients combined with stabilization of hematological parameters and spleen volume,” Claire Harrison, the chair of the safety review committee for the MYLOX-1 trial, and the Guy & St. Thomas NHS Foundation Trust, said in the press release. “Stable disease is excellent in a progressive disease such as myelofibrosis.”

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