MRG-106, an RNA-based therapy, induced clinical improvements in 90 percent of patients with mycosis fungoides – a subtype of cutaneous T-cell lymphoma (CTCL) – in a Phase 1 clinical trial testing the treatment.
Also, eight in 10 patients who received a 300 mg dose intravenously had an objective response, which is defined as a reduction by at least 50 percent in their skin lesions
“We believe that the clinical activity observed with MRG-106 in CTCL continues to demonstrate that patients are experiencing meaningful improvement in total skin disease and that MRG-106 is generally well-tolerated at all doses tested,” William S. Marshall, PhD, miRagen president and CEO, said in a press release.
The results were presented recently during the 10th Annual T-cell Lymphoma Forum in La Jolla, California. Christiane Querfeld, MD, PhD, chief of the Division of Dermatology, and director, Cutaneous Lymphoma Program at the City of Hope in Duarte, California, delivered the presentation, titled “Emerging Rationale for Targeting miRNA’s in CTCL.”
The ongoing Phase 1 study (NCT02580552), currently recruiting participants, is testing the effectiveness of MRG-106 in patients with different forms of lymphomas and leukemias, including the mycosis fungoides subtype.
The 29 mycosis fungoides participants received weekly doses of MRG-106 – 300 mg, 600 mg and 900 mg – delivered subcutaneously (under the skin) or intravenously (directly into the blood), or via intravenous bolus injection, which administers the therapy faster than the normal intravenous injection.
As of January 2018, 90 percent of patients had improved the severity of skin disease. The signs of improvement were noticeable only 17 days after the first dose of therapy, but the best outcomes were seen after one to two months of dosing.
Patients treated subcutaneously or intravenously for longer periods, and experiencing a decrease of at least 50 percent in mSWAT scores, maintained the skin improvements for more than four months.
Also, 80 percent of patients who received the 300 mg dose intravenously achieved an objective response, supporting its potential as the therapeutic dose to be tested in a future Phase 2 clinical trial.
miRagen is now discussing the U.S. Food and Drug Administration (FDA) the design of a Phase 2 clinical trial. The randomized trial will include an open-label, parallel group where patients will receive 300 mg of MRG-106 given intravenously, compared to an active control group.
The Phase 2 study plans to enroll about 65 patients per treatment group and will assess patients’ response to the therapy. Additional (secondary) endpoints include progression free survival – the time during which a patient lives with the disease without getting worse – and patient-reported outcomes.
The Phase 2 trial outcomes, if successful, may support miRagen’s application for accelerated approval of MRG-106.
“People suffering from CTCL have few treatment options available and some patients may be intolerant or become resistant to these treatments over time,” said Querfeld. “We continue to be encouraged by additional data from the Phase 1 clinical trial of MRG-106, providing further evidence that micro-RNA-based therapeutics, if approved, have the potential to significantly improve skin tumor burden for patients living with this disease.”