Anavex Life Sciences Corp (AVXL)

[Doc328]

Unlike a study, the reporting of adverse effects for SAS Cat B falls on the prescribing doctor.

Relevant passage from guidance

The prescribing health practitioner is primarily responsible for reporting adverse events or
defects arising from the use of unapproved therapeutic goods accessed under the SAS. The
prescribing health practitioner must report the details of any adverse events or defects to TGA
and the sponsor within 15 calendar days of becoming aware of them. These reporting
requirements apply equally to products accessed under all of the SAS pathways.
There are multiple ways in which adverse events and defects can be reported to the TGA (see
Reporting mechanisms).
Sponsors of unapproved products may also impose reporting requirements upon treating health
practitioners.

Sponsors receive safety information from the prescribing doctor as well. The sponsor is obligated to compile ALL safety information as part of the NDA submission. Unlike a clinical trial, however, Anavex is not responsible (via CRO) in proactively collecting safety data. For Cat B SAS it is unclear whether the sponsor has additional requirements such as filing annual summaries to the TGA. However, for US Right to try, the prescribing doctor also bears primary responsibility to report serious adverse events (SAE) to the sponsors AND the FDA. Additionally, the sponsor must file an annual report to the FDA including SAE's AND patient numbers.

One reason that few drug companies dispense drug for the general disease population (in comparison to the post-trial population) via these alternative pathways is that patients are not screened for general good health. Very sick or unstable patients, who would never have been in a study, developing SAE's can have a negative impact on the regulatory reviews. If a patient dies and the prescribing MD reports the case, this data will need to be included in NDA submissions.