Anavex Life Sciences Corp (AVXL)

[flsh56]

BINGO!! The last sentence!! That should just about cover the importance of biomarkers. Go Dr M!!

222 Because it is highly desirable to intervene as early as possible in AD, it follows that patients with
223 characteristic pathophysiologic changes of AD but no subjective complaint, functional
224 impairment, or detectable abnormalities on sensitive neuropsychological measures (Stage 1
225 patients) are an important target for clinical trials. A clinically meaningful benefit cannot be
226 measured in these patients because there is no clinical impairment to assess (assuming that the
227 duration of a trial is not sufficient to observe and assess the development of clinical impairment
228 during the conduct of the trial). In Stage 1 patients, an effect on the characteristic
229 pathophysiologic changes of AD, as demonstrated by an effect on various biomarkers, may be
230 measured. Such an effect, analyzed as a primary efficacy measure, may, in principle, serve as
231 the basis for an accelerated approval (i.e., the biomarker effects would be found to be reasonably
232 likely to predict clinical benefit, with a post-approval requirement for a study to confirm the
233 predicted clinical benefit). As with the use of neuropsychological tests, a pattern of treatment
234 effects seen across multiple individual biomarker measures would increase the persuasiveness of
235 the putative effect.
236
237 Although the issues and approaches discussed above for Stage 2 patients are relevant for Stage 1
238 patients, there is unfortunately at present no sufficiently reliable evidence that any observed
239 treatment effect on such biomarker measures would be reasonably likely to predict clinical
240 benefit (the standard for accelerated approval), despite a great deal of research interest in
241 understanding the role of biomarkers in AD. FDA strongly supports and encourages continued
242 research in this area and stresses its potential importance in the successful development of
243 effective treatments appropriate for use in the earliest stages of AD.