Why the rest periods?
The on-off blarcamesine (Anavex 2-73) dosing schedules in today’s patent application are most interesting. The company wouldn’t be laying this out unless it had data and experiences indicating efficacy.
According to the patent application, the drug will be given at full strength for an initial period, a few days or a week or so; followed by a “rest period.” This on-off dosing schedule then continues for a year or more.
How come? Why not just give a daily dose, without interruption, without “rest periods?” Far more convenient. There could be several reasons. Choose the one you thinks fits best.
1) After the first, initial dosing period, the drug loses efficacy; no longer suppresses or turns off Alzheimer’s symptoms. The cellular structures or processes the drug controls become saturated, so they need a rest period for the drug to clear and be able to resume efficacy when dosing re-starts.
2) For whatever exact mechanistic reason is at play, perhaps unknown, Anavex has discovered that intermittent dosings at the intervals laid out in the patent application actually work best, give the best therapeutic results.
3) As shown in early Phase 1 clinical trials, and in murines (lab rodents), continual, unvarying dosings do work; but symptomatic improvement curves flatten after long periods of continuous dosings. With dose rest periods, the drug maintains continuing high, uninterrupted levels of therapeutic efficacy.
4) For whatever reason(s), intermittent dosing simply works; so, with the rest periods, dosing costs are reduced by about a half, or more.
With many drugs there are at the start “loading doses,” strong doses that load biological systems to where they can be properly modulated by the drug. Then, after the loading period, lower, chronic (time-continuing) dosages are administered. This has not been mentioned for blarcamesine. This phenomenon would be investigated with dosage “titrations” in human clinical trials, where dosages are low at the start, but incrementally increased until therapeutic results appear. Then, that dosage level is continued.
After long durations of such symptomatic relief, some clinicians might then want to titrate down, to see if results continue at lower dosage levels.
