A biologics license application (BLA) for mogamulizumab as a CTCL therapy was accepted and granted priority review status by the U.S. Food and Drug Administration (FDA) on Nov. 28, 2017. The predicted FDA action date for the application is June 4, 2018.
How mogamulizumab works
CTCL is a type of blood cancer. It is caused by the abnormal behavior and growth of a type of white blood cell called T-cells. It is generally characterized initially by the migration of the cancerous cells into the skin.
Mogamulizumab is an antibody, a protein designed to interact with a one specific target. It binds to and inhibits an immune protein called C-C chemokine receptor 4 (CCR4), also known as CD194. CCR4 is commonly produced by T-cell lymphomas, including CTCL, and can promote the growth and movement of cancer cells into the skin.
CTCL may also reduce the body’s immune response against the cancer, resulting in the patient’s body being less effective at removing the cancer by itself. Mogamulizumab is produced using Kyowa Hakko Kirin’s proprietary Potelligent technology, which enhances the activation of a process called antibody-dependent cell-mediated cytotoxicity (ADCC) when mogamulizumab binds to CCR4.
This process results in the death of cancer cells, for example by recruiting of a type of immune cell called a natural killer (NK) cell to the tumor site.
Through these mechanisms, the goal of mogamulizumab is to slow or stop the progression of cancer.
Mogamulizumab in clinical trials
Mogamulizumab has been investigated in several clinical trials as a lymphoma therapy.
The key clinical trial supporting the company’s BLA is the Phase 3 MAVORIC study (NCT01728805). This study compared the safety and efficacy of mogamulizumab to Merck’s FDA-approved CTCL therapy Zolinza (vorinostat) in 372 previously treated patients with either mycosis fungoides (MF) or Sézary syndrome (SS), two types of CTCL. The MAVORIC trial is ongoing at 73 sites in North America, Australia, Europe, and Asia, but is no longer recruiting participants.
Results of the trial, presented at the 59th American Society of Hematology (ASH) annual meeting in December 2017, demonstrated that mogamulizumab had a significantly greater clinical benefit in both types of CTCL compared to Zolinza.
The investigator-assessed median progression-free survival (PFS) was 7.7 months with mogamulizumab, compared to 3.1 months with Zolinza.
An independent review estimated the difference to be slightly less pronounced, with a median PFS of 6.7 compared to 3.8 months, but the result was still highly significant.
Mogamulizumab also performed better than Zolinza in terms of overall response rate (ORR), at 28 percent compared to 4.8 percent across both disease subtypes. Individually, patients with MF had an ORR of 21 percent compared to 7.1 percent, and patients with SS had an ORR of 37 percent compared to 2.3 percent.
The safety profile of mogamulizumab was favorable compared to Zolinza. However, there was a higher incidence of infusion-related reactions and skin eruptions in patients taking mogamulizumab compared to Zolinza. But Zolinza caused a higher rate of diarrhea, nausea, thrombocytopenia (low platelet count), dysgeusia (a persistent unpleasant taste), and increased creatinine levels in the blood, a factor associated with kidney disease.
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