Wow...this is HUGE! Thanks MayoMobile. Excellent DD.
A2-73's recent P2 PDD trial results outperforms the Standard of Care (SOC) that is currently being given to PDD patients. (See comparisons below)
Comprehensive Review of 3 Large Levodopa Clinical Trials
I’ve been meaning to make a chart showing Levodopa (current PD SOC) efficacy but my computer has been acting up a bit. I don’t want to sit on this information any longer however. Below you will find clinical outcomes of three of the largest Levodopa trials I was able to find during my research.
* indicates point values are derived from a chart as the mean score was not provided openly *
361 patient trial of carbidopa-levodopa combination (40 week dose period & 2 week withdrawal)
*Placebo at 9 weeks: 0.1 to 2 points from baseline
*150mg at 9 weeks: -1 to -2.8 points from baseline
*300mg at 9 weeks: -3 to -5 points from baseline
*600mg at 9 weeks: -3.7 to -5.8 points from baseline
Placebo at 42 weeks: 7.8 points from baseline
150mg at 42 weeks: 1.8 points from baseline
300mg at 42 weeks: 1.8 points from baseline
600mg at 42 weeks: -1.4 points from baseline
Trial 1 Summary: overall this trial had generally good safety outcomes. When plotted, we can see how Levodopa is dose dependent. What Levodopa failed to do was provide clinically meaningful result. At 42 weeks, even the strongest dose yielded a very small -1.4 point improvement with all other doses succumbing to decline. It is reasonable to assume that with another few weeks, even the 600mg dose would see decline.
445 patient trial of carbidopa-levodopa combination (80 week dose period, 375mg dose)
Placebo for 40 week followed by dose for 40 weeks: -2 points from baseline at week 80
Dosed for 80 weeks: -1 point from baseline
Trial 2 Summary: once again we see relatively good safety data. This trials outcomes are very synergistic to the first trial in that Levodopa relief appears to fade with time, and even then, that relief does not meet clinically meaningful standards. Researchers of this trial assessed Levodopa is NOT disease modifying based on these outcomes, with efficacy falling off so quickly as time progresses.
222 patient trial of rasagiline-levodopa combination (52 week dose period 1mg/355mg)
Dosed at 6 weeks: -5.1 points from baseline
*Dosed at 10 weeks: -7.5 points from baseline
*Dosed at 18 weeks: -7.8 points from baseline
*Dosed at 26 weeks: -8 points from baseline
*Dosed at 34 weeks: -8.9 points from baseline
*Dosed at 42 weeks: -8.8 points from baseline
*Dosed at 52 weeks: -8.1 points from baseline
Trial 3 Summary: this Japanese study was by far the most clinically impressive Levodopa study. This benefit must be attributed to its combination with rasagiline. Unfortunately, rasagaline must also be responsive for a substantial patient drop off caused by safety concerns. In fact, 21% of the dosed cohort dropped out of this study due to adverse effects. Once again, we do start to see some fall off of efficacy as time progressed past 34 weeks, but overall doing well in the efficacy front.
Conclusion:
With Anavex UPDRS point values of -10.51 from BASELINE at week 14, Blarcamesine far exceeds efficacy over current standard of care. When looking back at the AD 2a data, we know that Blarcamesine efficacy is long-lasting at high doses and persists for multiple years as opposed to Levodopa. It seems clear that the TGA would like award priority review if applied given the excellent safety profile of Blarcamesine and its impressive clinical efficacy.
Note: I wanted to compare Annovis trial data, but no numerical values have been given towards their UPDRS data at this time.
