Share Price, page-10862

Hi Kens

With respect to DayBue efficacy:

• Firstly, the results you have provided were the Lavender CGI-I (physician rated) results, which is a more generalized measure of improvement used across multiple CNS disorders and considered to be not as sensitive as the condition-specific RSBQ scale.
• Whilst only 13% of patients recorded a much improved status on this measure, a further 24.7% showed a moderate level of improvement (minimally improved).
• So, using the less sensitive CGI-I scale, which is assessed by doctors, ~38% of Rett patients were showing signs of improvement after just 12 weeks.
• Twelve weeks is not a long time when measuring improvements in the brain. Hence, one needs to also look at the results over a longer period of time, that is, in the Lilac-1 (40 weeks) and Lilac-2 (104-144 weeks) extension studies.
• Modest continued improvement, using the CGI-I scale was seen by physicians at 40 weeks. The percentage of patients in whom improvement was seen had now risen from 38% to ~65%.
• The Rett-specific RSBQ scale was used for reporting by the parents. Like the physicians, parents also observed continued improvement over the course of the trials. An average 4.9 point improvement from baseline was seen at 12 weeks, a 7.3 point improvement at 40 weeks and 9.8 point improvement at 104 weeks (DayBue website).
• As explained by Dr. Dominique Pichard, IRSF’s CSO and also parent of a Rett daughter, even a 1 point improvement on a scale is meaningful for Rett families. It might represent, for example, a patient being able to hold a cup by herself or engage more non-verbally.
• Discontinuation rates due to reported lack of efficacy were relatively small. In the 40 week Lilac-1 trial, a 3.2% discontinuation rate was seen. For Lilac-2 (144 weeks combined), the reported discontinuation rate due to lack of efficacy was 3.9%.
• To provide some further context, adherence to long-term therapy for chronic illnesses in developed countries (for all reasons) averages just 50%. (World Health Organization, 2003). CNS drugs tend to have higher discontinuation rates. For example, for the blockbuster CNS drug, pregabalin, which was added to the PBS in Australia in 2013/14 for the treatment of refractory neuropathic pain not controlled by other medicines, the discontinuation rate (for all reasons) seen at 1 year was between 77% and 86%.

https://www.cell.com/med/fulltext/S2666-6340(24)00222-8
https://www.daybuehcp.com/open-label-extension/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444783/