Camargo Pharmaceutical Services: Mycapssa

Satisfactory resolution of these deficiencies is required before this application can be approved.

Satisfactory resolution of this deficiency is required before this application can be approved.

The data in the application demonstrate that Mycapssa and Sandostatin IR (listed drug) are not bioequivalent.

89.78% failed to meet the bioequivalence criteria.

Mycapssa dose-response relationship or the pharmacodynamic (PD) comparability (growth hormone and IGF-1) between Mycapssa and Sandostatin injection in your application.

Although meeting strict criteria for bioequivalence is not required for products reviewed under section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act, absence of bioequivalence between Mycapssa and the listed drug necessitated that you demonstrate the safety and effectiveness of Mycapssa with data generated in study CH-ACM-01.

Study CH-ACM-01 was a single-arm, open-labeled, cohort study with a planned primary efficacy endpoint assessment that was to take place 7 months after a baseline assessment.

There were no formal inferences pre-specified and the study was to be purely descriptive in nature.

We noted in our review of the application that you had not pre-specified or selected which responder criterion you would use to define response for the purpose of presenting the primary efficacy results in the protocol submitted to the Agency at the End-of Phase-2 (EOP2) meeting.

We disagree with the response criterion that you ultimately selected for the primary efficacy analysis because your criterion is insensitive to detecting small but clinically meaningful changes in disease control.

From a clinical standpoint, it is likely that a sustained 50% increase in IGF-1 levels in 7 months in the example patient described would represent a clinically meaningful change in disease activity.

Furthermore, in a study designed to evaluate "loss of control" choice and use of a more conservative failure criterion to estimate drug effect is more likely to represent substantial evidence.

Finally, we also noted that the DMC was getting routine aggregate efficacy updates with each DMC meeting reports (i-e., not for cause and not for the purpose of determining futility per the charter).

To address the deficiency listed in item number 2, you will need to provide substantial evidence that Mycapssa will have the effect it purports to have under the conditions of use recommended in labeling for patients with acromegaly in a new clinical trial.

We encourage you to request an End of Review meeting to discuss the path forward for this application.