Trial PAR008 is on ANZCTR, page-65

There are a lot of issues with LOR which make it difficult to ascertain whether it will be considered favourably by the FDA, so I wouldn't consider it competition just yet. Here are some of the concerns the FDA are likely to have:

1. It was a post-hoc analysis from a failed study.

2. Background analgesia makes it difficult to determine the extent of the effect due to LOR.

3. Dropouts were excluded from analysis. Dropouts are most likely non-responders. FDA will perform sensitivity analysis and will treat dropouts as non-responders, which will negatively impact on the overall results.

4. The type of analysis performed was responder analysis, which you have to be cautious of when interpreting these results. For responder analysis you need to be able to identify who will respond to your treatment beforehand, which they are unable to just yet.

For the responder analysis, responders were compared groupwise between the LOR and PBO groups and logistic regression was performed on the full analysis set with non-responder imputation. These are not stringent forms of analyses, particularly imputation.

Article: Comparisons against baseline within randomised groups are often used and can be highly misleading
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3286439/

5. The dosage results are inconsistent and not dose dependent. Why does 0.07 LOR dose 'work', but not 0.15? The overall number of participants in this group were small ~ 60-70 participants in each group.

6. Type 1 error control was not employed in the post hoc response analysis, so you can't trust the p values.

7. There are no objective measures supporting their findings i.e. no MRI scans.

The best case scenario for LOR is it will be considered as part of the treatment algorithm that will also include iPPS, but they still have a mountain to climb.