Acadia breaks the Rett curse
After years of clinical failures in Rett syndrome Acadia has finally given patients hope. In the pivotal 187-subject Lavender trial, the group's trofinetide managed to hit both of its co-primary endpoints, showing improvements from baseline in two common Rett scores. At 12 weeks, trofinetide-treated patients had a 5.1-point decline on the RSBQ versus a 1.7 drop with placebo (p=0.0175), while CGI-I scores were 3.5 and 3.8 points respectively (p=0.0030). Although both results were highly significant, some analysts questioned the relatively small absolute benefit seen. However, with no approved therapies for Rett any improvement in symptoms will be welcomed. Indeed, Acadia had a 8% share price lift today, helped by low expectations for success following multiple failures in the disease. The group expects to file for approval of trofinetide in mid-2022. The only sticking point could be the IGF-1 analogue’s side effects; almost 81% of patients in the active cohort experienced diarrhoea, versus 19% on placebo, with 12% of those on trofinetide discontinuing treatment. However, Acadia said this problem could be addressed by patients discontinuing drugs to treat constipation, a common problem in Rett syndrome.
|Phase 3 pipeline for Rett syndrome|
|Project||Company||Mechanism of action||Indication sales 2026e ($m)||Primary endpoint|
|Trofinetide Oral||Acadia Pharmaceuticals||Insulin-like growth factor 1 regulator||161||RSBQ,CGI-1 at 12 weeks (Lavender study)|
|Anavex 2-73 (blarcamesine)||Anavex Life Sciences/Neuren Pharmaceuticals||Muscarinic acetylcholine receptor regulator; Sigma-1 receptor agonist||192||RSBQ,CGI-1 at 12 weeks (Excellence study)|
|RSBQ: Rett syndrome behaviour questionnaire total score, CGI-I: clinical global impression-improvement. Source: Evaluate Pharma.|