FDA Grants Orphan Designation to Cobomarsen for T-Cell Lymphomas

The FDA has granted an Orphan Drug designation to cobomarsen for the treatment of patients with T-cell lymphoma, according to an announcement from miRagen Therapeutics.

The FDA has granted an Orphan Drug designation to cobomarsen (MRG-106) for the treatment of patients with T-cell lymphoma, according to an announcement from miRagen Therapeutics.1

Cobomarsen is an investigational miR-155 inhibitor; miR-155 is typically found at high rates among many blood cancers, and it plays an important role in the differentiation, function, and proliferation of blood and lymph cells and inhibition of the microRNA may reduce the proliferation of cancerous cells. The agent is currently being investigated in a phase 2 clinical trial for patients with a form of cutaneous T-cell lymphoma (CTCL) as well as in a phase 1 trial of patients with adult T-cell leukemia/lymphoma (ATLL).

“This is an important milestone in the development of cobomarsen. We believe the FDA’s decision to grant cobomarsen Orphan Drug designation underscores the need for new treatments for T-cell lymphomas such as ATLL and CTCL,” stated William S. Marshall, PhD, miRagen president and CEO, in a press release. “In addition to the promising results we’ve observed for the potential treatment of patients with ATLL and CTCL, we believe that cobomarsen has the potential to be a broad-based therapy for the treatment of patients [with cancer] with elevated levels of miR-155.”

In the ongoing randomized, open-label, multicenter, parallel-group SOLAR trial, investigators are assessing the safety and efficacy of cobomarsen compared with the HDAC inhibitor vorinostat (Zolinza) in patients with the mycosis fungoides (MF) subtype of CTCL (NCT03713320). In the study, about 120 patients were randomized 1:1 to either cobomarsen administered on days 1, 3, 5, and 8, then weekly via 2-hour intravenous infusion, or daily oral vorinostat. Treatment continued in both arms until progression of disease.

All those who progressed on vorinostat during the study were able to cross over to receive cobomarsen in the PRISM study (NCT03837457).

Eligible patients included those with clinical stage Ib-III disease who had received at least 1 prior therapy for CTCL and had a minimum mSWAT (modified Severity Weighted Assessment Tool) score of 10. Those who had previously received cobomarsen or vorinostat as well as patients with Sézary syndrome or MF with B2 involvement, large cell transformation, visceral involvement, or visceral involvement at baseline were not able to participate in the trial.

The primary end point of the SOLAR trial is objective skin response for at least 4 months by mSWAT, and secondary end points included progression-free survival, complete response rate, skin disease severity, time to progression, and safety. The trial is continuing but no longer recruiting patients.

In a prior dose-ranging phase 1 study of cobomarsen in 43 patients with CTCL and MF subtype, 62% of patients achieved a partial response at the 300-mg dose level. Across all dosages, 92% of patients showed an improvement in mSWAT score.2

Of the 13 patients who achieved a partial response, 69% were maintained for at least 4 consecutive months with a mean duration of response of 259 days (range, 48-560+).

Cobomarsen is also being investigated in a phase 1 study in patients with MF, chronic lymphocytic leukemia (CLL), activated B-cell diffuse large B-cell lymphoma (ABC DLBCL), and ATLL (NCT02580552). In part A of the study, cohorts of 3 to 6 patients with MF will receive up to 5 intratumoral injections of cobomarsen for up to 15 days at various doses and then followed for 20 days. In parts B through F, patients with MF, CLL, ABC DLBCL, and ATLL will receive subcutaneous or intravenous cobomarsen on days 1, 3, and 5 followed by weekly administration, and treatment will be continued until disease progression, intolerance, or unacceptable toxicity.

For patients with MF, participants must have stage I-III disease and must be refractory to or intolerant of established treatments. Participants with CLL must be intolerant to or relapsed after at least 2 prior lines of therapy. For patients with DLBCL, they must be intolerant to or relapsed after at least 2 prior lines of therapy, including an anti-CD20 monoclonal antibody and curative chemotherapy. Participants with HTLV-1 infection and ATLL of any stage must be intolerant to or relapsed after at least 1 prior lines of therapy.

Those with renal or liver dysfunction, anemia, neutropenia, thrombocytopenia, bleeding or coagulopathy, cardiovascular disease, HIV, or other prior malignancies were ineligible for the trial.

The primary end point is the safety and tolerability of cobomarsen.


1. Cobomarsen receives orphan drug designation from the U.S. FDA for the treatment of T-cell lymphoma. News release. miRagen Therapeutics Inc. July 23, 2020. Accessed July 24, 2020. https://bit.ly/2ZTThxQ

2. Foss FM, Querfeld C, Pinter-Brown L, et al. Phase 1 Trial of Cobomarsen, an Inhibitor of miR-155, in Mycosis Fungoides. Blood. 2018;132(suppl 1):2903. doi:10.1182/blood-2018-99-119861