Perhaps the Australian government definition might help?
" Criterion 4: Justification of major therapeutic advance
You must provide a justification that there is preliminary evidence that the medicine is a major therapeutic advance based on the following aspects:
the magnitude of the demonstrated improvement in safety and/or efficacy
the likelihood of the early data or surrogate endpoints to predict clinical benefit
the impact on patient outcomes taking into account both safety and efficacy
the magnitude of the advance in relation to other therapeutic goods registered for the indicated population. Where no product is registered on the ARTG, the comparison should occur against the accepted standard of care
the strength of the preliminary evidence, characterising the uncertainty (general TGA adopted guidelines about appropriate trial design apply)
You must include an assessment of the magnitude of the demonstrated improvement in safety or efficacy based on preliminary data (including surrogate endpoints). The demonstration of a medicine's clinically significant benefit based on improved safety and/or efficacy is not sufficient. Rather, there should be demonstration of a major benefit, i.e. beyond the level that could be described as clinically significant. Due to the uncertainty around the benefits and risks that are demonstrated by the available preliminary data, the observed effects would be expected to translate into a major clinical benefit in order to meet this criterion (for example a major improvement in mortality endpoints). Even if the benefit appears in one aspect only, you must assess the overall impact on patient outcomes taking into account both safety and efficacy.
The medicine should provide a therapeutic advance, in comparison with other registered therapeutic goods, where possible, by addressing a major or urgent unmet need for Australian patients in a substantial way. You must describe how and to what extent the medicine is expected to fulfil a major or urgent unmet medical need with reference to the therapeutic goods registered for the indicated population, the importance of the effects of the proposed medicine, and the added value of the proposed medicine.
The description of the strength of the preliminary evidence should include a brief outline of the main available evidence (for example number and type of clinical interim or final trials with clear delineation of pivotal versus supporting studies, sample size, design and key results) on which the claim is based. In the context of preliminary data, weak data evidence would be weighted less than comprehensive data evidence. See Justification of significant improvement in safety or efficacy for further information on cross study comparisons.
A medicine that demonstrates significant improvement in safety or efficacy may constitute a major therapeutic advance if for example, the medicine that demonstrates cure rates that are considerably higher than those observed in previous treatment options, while also replacing a standard treatment which has poor tolerability and potential for serious side effects."
I would say that Anavex 2-73 fits these criteria very well!
"The refusal of the real is the number one dogma of our time" Rene Girard
