Astellas Pharma Inc. has announced the submission of a European marketing authorisation application to the European Medicines Agency (EMA) for enzalutamide (USAN*, MDV3100) for the treatment of men with metastatic castration-resistant prostate cancer who have been previously treated with docetaxel-based chemotherapy.

Enzalutamide, is a novel, once-daily investigational oral androgen receptor signalling inhibitor and the submission follows positive results from the pivotal phase III AFFIRM study, which confirmed that enzalutamide demonstrated a statistically significant improvement (p<0.0001) in overall survival with a median improvement over placebo of 4.8 months [hazard ratio (HR) = 0.631].

The study also concluded that enzalutamide was generally well tolerated by patients and met all secondary endpoints. A New Drug Application (NDA) has been submitted in the United States, where priority review of the compound has been requested.

"Data from clinical studies, including the phase III AFFIRM study, have demonstrated that enzalutamide significantly improves overall survival whilst providing a favourable tolerability profile for patients," said Professor Johann de Bono, M.D., MSc, Ph.D., FRCP, Honorary Consultant in Medical Oncology, Professor in Experimental Cancer Medicine, The Institute of Cancer Research, The Royal Marsden Hospital and co-principal investigator of the AFFIRM study.

“This is vital for patients at this late stage of their disease and the submission of enzalutamide represents an important step towards making this promising treatment available to men with advanced prostate cancer across Europe."

Further positive data from the AFFIRM study relating to the secondary endpoints of health-related quality of life and time to first skeletal-related events will also be presented this week at the Global Congress on Prostate Cancer, Brussels, Belgium.

These data demonstrate that treatment with enzalutamide resulted in a significantly higher response rate in health-related quality of life as compared to placebo (43.2 percent vs. 18.3 percent; p<0.0001), as measured by the Functional Assessment of Cancer Therapy – Prostate (FACT-P) questionnaire.

The FACT-P is a validated instrument comprising 27 core items to assess patient function (e.g., level of energy, ability to cope with illness, level of pain, ability to work, and amount of support from family/friends). Patients were defined as having a health-related quality of life response using the standard definition of 10 point or greater improvement in their overall score.

In addition, the median time to occurrence of the first skeletal-related event in enzalutamide treated patients was 16.7 months as compared to 13.6 months with placebo (p=0.0001, HR=0.621). 3 A skeletal-related event was defined as a pathologic bone fracture, change of anti-cancer therapy to treat bone pain, spinal cord compression, or surgery or radiation therapy to bone.

In the phase III AFFIRM trial, common side effects observed more frequently in enzalutamide as compared with placebo-treated patients included fatigue, diarrhoea and hot flush. Seizure was reported in < 1% of enzalutamide-treated patients. Serious adverse events, adverse events causing patients to stop treatment, and adverse events causing death were all lower in the enzalutamide group than in the placebo group.

These data form one of four winning abstracts at the congress and will be presented by Professor Cora Sternberg of the Department of Medical Oncology, San Camillo Forlanini Hospital, Rome, Italy.

“Extending life for patients with advanced prostate cancer is of course a primary goal of treatment, but equally important is that we minimise the impact of treatment on patient quality of life”, said Professor Sternberg. “These data demonstrate that enzalutamide provided a significantly higher level of quality of life for these patients and also extended the time to occurrence of skeletal-related events, a serious complication of the disease which can cause significant pain and morbidity.”

Source: Astellas