Regulatory Decision Summary for Rydapt

Data to support the efficacy and safety of Rydapt in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation chemotherapy for the treatment of adult patients with newly diagnosed FLT3-mutated AML are provided from the pivotal study A2301 (RATIFY) and eight supportive studies.

Study A2301 is a phase III, randomized, double-blind study of Rydapt vs. placebo in combination with standard cytarabine and daunorubicin induction and high-dose cytarabine consolidation chemotherapy conducted in 717 patients with newly diagnosed FLT3-mutated AML.

The primary endpoint was overall survival (OS), where the analysis was conducted after a minimum follow-up of ~3.5 years after the randomization of the last patient. Statistically significant improvement in OS was observed with a 23% risk reduction of death for Rydapt plus standard chemotherapy over placebo plus standard chemotherapy. The key secondary efficacy endpoint, event-free survival non-censored at the time of stem cell transplant, also demonstrated the benefits of Rydapt plus standard chemotherapy over placebo plus standard chemotherapy.

The most frequent adverse drug reactions (ADRs) in the Rydapt arm were febrile neutropenia, nausea, exfoliative dermatitis, vomiting, stomatitis, headache, petechiae, pyrexia, epistaxis, hyperglycemia, back pain and device related infections. The most frequent Grade 3/4 ADRs were febrile neutropenia, lymphopenia, device- related infection, and exfoliative dermatitis. There were also notable adverse events of QT prolongation, cardiac toxicity (cardiac failure), neutropenia and infection, and pulmonary toxicity (interstitial lung disease and pneumonitis). There is limited data for patients aged 60-70 years old and no data in patients above 70. Rydapt should not be used in women who are pregnant or contemplating pregnancy. The Product Monograph is the primary risk management strategy to manage the risks associated with Rydapt. It provides warnings pertaining to the significant adverse events reported in clinical trials, and recommendations to the prescriber regarding dose modifications/interruptions that may be required to manage adverse events. Recommendations for monitoring are also provided.

The combination of Rydapt with standard cytarabine and daunorubicin induction and cytarabine consolidation chemotherapy has demonstrated to be an effective treatment for adult patients with newly diagnosed FLT3-mutated AML in which there is an unmet medical need. Based on the data reviewed, the benefit-harm-uncertainty assessment is considered to be positive.

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