Regulatory Decision Summary for Yescarta

The authorization was based on one pivotal clinical study, ZUMA-5, which was a single arm, phase 2, open-label, multicenter study of Yescarta in patients with indolent non-hodgkin lymphoma. Patients with r/rFL (n = 124) received a single-infusion of axicabtagene ciloleucel.

The study met its primary outcome by demonstrating a clinically significant Objective Response Rate of 94% (95%CI: 87, 98) in the set of patients (n = 80) who were enrolled, received Yescarta, and had the opportunity to be followed for 12 months after the first disease assessment. The Complete Response (CR) rate was also clinically significant at 80% (95% CI: 70, 88). Both results were statistically significant improvements over the pre-specified null hypotheses. Responses were durable with a median duration of response not estimable at the time of the primary analysis. Notably, the ORR and CR rates were similar between the inferential analysis set and the fully enrolled analysis set.

The most important risks of Yescarta treatment are cytokine release syndrome (CRS) and neurological toxicities. CRS was observed in the majority of subjects who participated in ZUMA-5. This finding is consistent with the findings of trials of Yescarta in other diseases such as large B-cell lymphoma. Neurological toxicity may manifest as a variety of neurological adverse events including tremor, confusion, or encephalopathy. Monitoring and recognition for CRS and/or neurological toxicities is critical and the management of such events includes the use of corticosteroids and tocilizumab. Yescarta increases the risk of prolonged cytopenias, hypogammaglobulinemia and infection. However, these risks are usually manageable through a combination of monitoring and infection precautions such as antibiotic prophylaxis and/or immunoglobulin replacement.

Given the high rates of response observed, including a majority of complete responses, which have proven to be relatively durable. And, given the experience gained in the management of a toxicity profile that is remarkable, but manageable through treatment in specialised cancer centres, close monitoring, and the use of corticosteroids and tocilizumab, the benefit of Yescarta treatment for patients with relapsed or refractory follicular lymphoma, as labelled, is considered to outweigh the risks of treatment.