Regulatory Decision Summary for Erleada

This Supplement to a New Drug Submission for Erleada was filed to seek approval for a new strength consisting of film coated (FC) tablets of 240 mg. Erleada is currently commercially available as a FC tablet at the strength of 60 mg. The recommended clinical dose is 240 mg taken with or without food as 4 x 60 mg FC tablets. The new 240 mg tablet was developed with the purpose of reducing the pill burden for patients (from 4 to 1 daily tablet) and to enhance compliance in patients who might be taking several medications for co-morbidities. In addition, a new administration method through a nasogastric tube has been introduced for the 240 mg format to offer a suitable option to patients with difficulties swallowing.

Erleada (apalutamide) is an anti-androgen indicated for the treatment of patients with metastatic castration-sensitive prostate cancer (mCSPC) and the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC). Erleada is currently marketed in Canada as 60 mg Film-Coated (FC) tablets and the recommended dose is 240 mg per day. With this submission, the sponsor is proposing the introduction of a 240 mg tablet strength.

This drug product is manufactured by dry granulation of intra-granular excipients with the previously approved spray dried powder dispersion containing the drug substance (also used for the manufacture of the 60 mg tablets), followed by blending with extra-granular excipients, lubrication, compression and non-functional tablet film-coating. The formulation and manufacturing process used for the 240 mg strength lot(s) used in the pivotal bioequivalence trial of the approved 60 mg tablets and proposed 240 mg tablets have been found to be representative of those proposed for the commercial lots. The administration instructions for both alternate administration methods (dispersed in water or soft food or through a NG tube) are adequately supported by compatibility and in use stability studies. Comparative chemical and manufacturing documentation supported the additional methods of administration of the 240 mg strength tablets and it was considered to comply with the Quality data requirements of Section C.08.003 of the Food and Drug Regulations.

The results of Study 56021927PCR1028 demonstrated that the rate and extent of absorption of apalutamide from the currently marketed Erleada 60 mg tablets administered as 4 x 60 mg tablets under fasting conditions and the proposed Erleada 240 mg tablet administered as 1 x 240 mg tablet under fasting conditions are considered comparable and that food has no effect on the rate and extent of absorption of apalutamide. Therefore, the two strengths, namely 60 mg and the proposed 240 mg are comparable in terms of bioavailability and food effects. As such, the proposed Erleada (apalutamide) tablets 240 mg are considered to meet the requirements of the Food and Drugs Act and Regulations.

A new route of administration through a nasogastric feeding tube, following dispersion of the tablet in non-carbonated water, was also proposed for the new 240 mg tablet. In-use compatibility and in-use hold time studies showed that when the 240 mg tablet is dispersed in water and administered via a nasogastric tube (NG), the quality parameters of the formulation were preserved. This alternate method of administration is considered a valuable option for patients who have difficulty swallowing and was added to the Erleada product monograph.

The labelling documents reviewed conform to the necessary regulatory requirements and were considered acceptable.

Overall, the proposed Erleada (apalutamide) tablets 240 mg and new administration instructions are considered to have a benefit-harm-uncertainty profile that is favorable under the approved conditions of use.