miRagen Therapeutics has announced new interim results from its ongoing phase 1 clinical trial evaluating the safety, efficacy and pharmacokinetics of MRG-106 in patients with the mycosis fungoides (MF) form of cutaneous T-cell lymphoma (CTCL).
The data is being presented at the European Organisation for Research and Treatment of Cancer (EORTC) Cutaneous Lymphoma Task Force Meeting in London, United Kingdom, by Christiane Querfeld, M.D., Ph.D., Chief of the Division of Dermatology, and Director, Cutaneous Lymphoma Program at the City of Hope in Duarte, California.
“We are encouraged by the new MRG-106 Phase 1 data, as we observed that 96% of patients treated systemically experienced improvement in total skin disease at all dose levels evaluated,” said miRagen President and CEO William S. Marshall, Ph.D. “These findings suggest that MRG-106 has the potential to offer meaningful benefit to patients with CTCL. We are making what we believe to be important progress for patients in our MRG-106 Phase 1 clinical trial, and we were pleased to share these new data with the medical community.”
The MRG-106 Phase 1 trial consists of two parts. In the first part, patients were treated with 75 mg injections of MRG-106 directly into a specific lesion. These data, which showed a decrease in lesion size for all injected lesions, have been previously presented. The second part employed a multiple dose-escalation design to evaluate 300 mg, 600 mg or 900 mg subcutaneous or intravenous administrations of MRG-106. The newest results to be reported at EORTC include observations from four additional patients as well as longer term dosing data for existing patients who have continued on the trial. Interim data from the second part of the Phase 1 trial are summarized below:
Twenty-two of twenty-three patients (96%) treated systemically showed improvement in total skin disease as measured by the maximal change in each patient’s modified Severity Weighted Assessment Tool (mSWAT) score, which assesses the severity of skin disease over a patient’s entire body.
Nine of thirteen patients treated for more than one month showed a 50% or greater maximal improvement in mSWAT scores.
Responses in mSWAT of 50% or greater appeared to be durable for all patients who continued on therapy. Additionally, to date five patients maintained a durable response for four months or longer.
The magnitude of mSWAT improvements appeared to correlate with amount of time the patient received MRG-106 treatment.
In patients who showed improvements, these were observed regardless of whether the patient was receiving background medication(s) for CTCL or MRG-106 alone.
MRG-106 has been generally well-tolerated for all 27 patients evaluated to date at dose levels ranging from 75 mg to 900 mg.
Injection site reactions were seen in some patients after subcutaneous administration and were generally minor and self-limited.
Only one patient had a Grade 3 adverse event, worsening of pruritus (itchy skin) compared to baseline, which was considered potentially related to MRG-106 administration.
“The new MRG-106 Phase 1 data build upon those presented throughout the year, and to date has been generally well-tolerated with preliminary indications of clinical response,” said Paul Rubin, M.D., miRagen’s Executive Vice President of Research and Development. “We are encouraged by these results, which we believe support advancing MRG-106 into controlled clinical trials next year.”
The interim results announced by miRagen are from an ongoing Phase 1 trial in patients with documented mycosis fungoides. In part 1, patients were treated with 75 mg injections of MRG-106 directly into a specific lesion. Part two, of the trial which is currently enrolling, employs a multiple dose-escalation design to evaluate 300 mg, 600 mg or 900 mg subcutaneous or intravenous administrations of MRG-106. Patients were allowed to continue background medication provided these have remained unchanged for one month prior to receiving MRG-106. Enrolled patients receive a one week loading regimen followed by weekly dosing with 300 to 900 mgs through IV or subcutaneous administration. Patients are monitored for safety, and for improvement in skin disease via mSWAT at regular intervals throughout the trial.
MRG-106 is an inhibitor of microRNA-155. In CTCL, as well as certain other blood cancers, microRNA-155 is present at abnormally high levels, and may play a role in the proliferation of blood and lymph cells. miRagen believes therapeutic inhibition of microRNA-155 may reduce aberrant cell proliferation and the tumor growth characteristic of certain types of cancer.
miRagen plans to evaluate MRG-106 in additional oncology indications within the current Phase 1 trial, including adult T-cell leukemia/lymphoma, diffuse large B-cell lymphoma and chronic lymphocytic leukemia as in each case the disease process appears to be related to an increase in miR-155 levels.