Issue

Homebrew installs in either a default directory (based on factors such as the macOS version installing Homebrew, the Homebrew version being installed, etc.) or a user-specified directory.

Homebrew provides a HOMEBREW_PREFIX environment variable in order to locate where it's installed.

While setup.py takes a few guesses as to where Homebrew is located (setup.py#L213-L219), it does not use the environment variable which is likely to have the location:

If the user installed Homebrew in a user-specified directory, setup.py is not able to find Homebrew and fails to run.