Regulatory Decision Summary for Poteligeo

Poteligeo(mogamulizumab) was authorized based on the results from a multicenter, open-label, randomized (1:1), active controlled (vorinostat) phase 3 study (Study 0761-010) in 372 adult patients with r/r MF (55%) or r/r SS (45%) treated with at least one prior systemic therapy. 186 subjects in each arm received the recommended doses.

The progression-free survival (PFS) per investigator assessment (IA) was statistically significantly longer in the Poteligeo-treated subjects (the estimated median 7.5 months) than in the vorinostat-treated subjects (the estimated median 3.1 months) with an estimated 47% reduction in the risk of progression or death in the control arm.

In addition, the confirmed objective response rate (ORR) by IA based on global composite response criteria was statistically significantly higher in the Poteligeogroup (28%) compared to the vorinostat group (5%).

A 47% reduction in the risk of disease progression or death in a highly treated population can be considered clinically meaningful. In addition, although MF has a median survival of 20 years, SS has a median survival of 3.1 years. The survival of subjects with r/r MF or SS is likely less than 3.1 years. The estimated median of 7.5 months of PFS in the Poteligeogroup can be considered as clinically meaningful.

The efficacy results appeared to be driven by SS and there are emerging data suggesting that SS and MF may be distinct entities with differing pathogenesis.

The treatment-emergent adverse events (TEAEs) were comparable between the two arms. In the Poteligeoarm, the most frequently reported TEAEs were infusion-related reaction (IRR) (33.2%), drug eruption (22.8%), fatigue (18.5%), and diarrhea (10.3%). The most frequently reported serious adverse reactions were pneumonia and pyrexia (2.2% each), cellulitis and IRR (1.6% each), and sepsis, respiratory failure, increased liver enzymes and drug eruption (1.1% each). Fatalities occurred in 2 (1.1%) Poteligeo-treated subjects (polymyositis and sepsis, 1 each).

Compared to the vorinostat group, other than serious adverse reactions (16.9% in vorinostat group vs. 19.6% in the Poteligeogroup), the incidences of the following adverse reactions (moderate to severe severity, reactions leading to death, and leading to drug discontinuation) were lower in the Poteligeogroup. 

Adverse events of special interest identified based on mechanism of action, clinical trial and post-market data included IRRs, infections, dermatologic toxicity (rash and severe cutaneous adverse reactions), tumor lysis syndrome, stress cardiomyopathy, and immune-related AEs.

In the literature, Poteligeouse has been associated with increase risks of graft-versus-host disease (GVHD) in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) after Poteligeo, hepatitis B reactivation and cytomegalovirus (CMV) related infection.

All identified and potential adverse reactions were labelled in the Product Monograph.

In adult patients with r/r MF or r/r SS after at least one systemic therapy, the benefit/risk profile of Poteligeois considered acceptable. A Notice of Compliance was issued.

For more information on Health Canadas decision, please view the Summary Basis of Decision.