The European Medicines Agency (EMA) agreed to review documents supporting the approval of mogamulizumab — an antibody targeting the CCR4 protein — as a treatment for adults with cutaneous T-cell lymphoma (CTCL) who have received at least one prior systemic therapy.
Kyowa Kirin, the therapy’s developer, submitted a marking authorization application to the EMA based on encouraging results from the ongoing Phase 3 MAVORIC study (NCT01728805), the largest global and randomized clinical trial of a systemic therapy in CTCL patients.
Mogamulizumab, under the brand name Poteligeo, has been approved in Japan to treat other blood cancers since 2012, and for CTCL patients since 2014.
MAVORIC’s full results will be announced at the 59th ASH Annual Meeting & Exposition on Dec. 11, in a presentation titled “Anti-CCR4 Monoclonal Antibody, Mogamulizumab, Demonstrates Significant Improvement in PFS Compared to Vorinostat in Patients with Previously Treated Cutaneous T-Cell Lymphoma (CTCL): Results from the Phase III MAVORIC Study.” Under ASH policy, information in abstracts can be published once the abstract is available online.
The Phase 3 study’s primary outcome is to compare the time to disease progression, or death, in patients with relapsed/refractory CTCL assigned to mogamulizumab versus those who receive Zolinza (vorinostat). Zolina, developed by Merck, is a histone deacetylase (HDAC)-inhibitor approved to treat CTCL patients who have progressive, persistent, or recurrent disease following two systemic therapies.
MAVORIC enrolled 372 patients, who were randomized to received 1.0 mg/kg of mogamulizumab (weekly for the first four-week cycle and then every two weeks) or 400 mg Zolinza administered daily. Those on Zolinza were allowed to switch to mogamulizumab upon signs of disease progression or intolerable toxicity.
The study, conducted at 73 research centers in Japan, North America, Europe, and Australia, is following patients for 36 months. It is set to finish in December 2018.
Results from an initial investigator assessment showed that mogamulizumab significantly delayed disease progression compared to Zolinza, with a median progression-free survival (PFS) of 7.7 months versus 3.1 months, respectively.
A later independent review largely confirmed these results, finding a PFS of 6.7 months in mogamulizumab-treated patients compared to 3.8 months in those given Zolinza.
The global overall response rate (ORR) — defined as the portion of patients showing a predefined reduction in tumor size over a set minimum time — was 28 percent in patients randomized to mogamulizumab, and 4.8 percent in those on Zolinza. The response rate was even higher in patients who crossed from Zolinza to mogamulizumab, with an ORR of 30.1 percent.
Mogamulizumab-treated patients also reported a significant easing of disease symptoms and improved functional status since early treatment cycles, with these benefits continuing during the trial period.
“This is a significant milestone for our subsidiary, Kyowa Kirin Pharmaceutical Development,” Mitsuo Satoh, vice president and head of the R&D Division of Kyowa Hakko Kirin, based in Japan, said in a press release. “I believe mogamulizumab has the potential to be an advance in therapy for patients with CTCL and we will keep working to make it available to patients as soon as possible.”
The most common treatment-emergent adverse events in mogamulizumab-treated patients included infusion-related reactions and skin eruptions, and were largely considered mild to moderate in severity. Those more frequent in the Zolinza arm included diarrhea, nausea, thrombocytopenia (low blood platelet count), dysgeusia (distortion of the sense of taste), and increased blood creatinine.
Mogamulizumab was named a breakthrough therapy as a potential CTCL treatment by the U.S. Food and Drug Administration (FDA) this year.
Kyowa Hakko Kirin announced it is also beginning discussions with regulatory authorities in other countries regarding mogamulizumab’s possible approval to treat CTCL patients.