PSI-GAD Generalised Anxiety Disorder
About
Incannex, are investigating the use of psilocybin assisted psychotherapy to treat of Generalised Anxiety Disorder (GAD).
Treatment of GAD with standard of care antidepressant medications and therapies remains inadequate, with less than half of patients achieving remission. Psilocybin-assisted psychotherapy has shown promise in the treatment of several other mental health conditions.
Program overview
In 2020, Incannex partnered with Monash University to conduct a phase 2 clinical trial to assess psilocybin-assisted psychotherapy to treat patients with generalised anxiety disorder (GAD), a unique and proprietary form of therapy called PsiGAD. Dosing for this study (PsiGAD-1) was completed in January 2024. Topline results were released in February 2024.
The trial protocol and treatment design were developed in partnership with the Clinical Psychedelic Lab at Monash University, led by Dr Paul Liknaitzky.
PsiGAD-1 was a randomised triple-blind active-placebo-controlled Phase 2 trial assessing psilocybin assisted psychotherapy for treatment of GAD. The study aimed to recruit 72 GAD patients with the primary objective being to determine whether a 7-week program of psilocybin-assisted psychotherapy for GAD is superior to active placebo-assisted psychotherapy in decreasing symptoms of GAD, as measured by the change in the Hamilton Anxiety Rating Scale (HAM-A) from baseline to week 11. Safety and tolerability were assessed, as well as other secondary objectives of efficacy and quality of life.
Topline results from the PsiGAD-1 trial supported the safety and efficacy of PsiGAD for treatment of GAD. The reduction in HAM-A score from baseline in the psilocybin group was 12.8 points, from 29.5 at baseline to 16.8 at week 11 (6 weeks following the final dosing session), representing a decrease of 9.2 points over the placebo group (-12.8 psilocybin vs. -3.6 placebo; p<0.0001). 44% of patients in the psilocybin group showed a clinically meaningful improvement of at least 50% reduction in anxiety score from baseline; a ‘response rate’ more than four times higher than that of the placebo group. 27% of patients in the psilocybin group achieved full disease remission; a rate more than five times higher than that of psychotherapy with placebo.
Psilocybin within the context of PsiGAD psychotherapy was observed to be well-tolerated, with only mild and moderate adverse events (AEs) reported. The reported AEs were consistent with the known effects of the drug. No serious or severe adverse events were observed. Only one person of the 73 participants withdrew from the trial during the 7-week treatment program.
Incannex have designed the follow-up Phase 2B clinical trial, PsiGAD-2. This trial will be conducted at multiple sites in the United States (US) and United Kingdom (UK).
In parallel, Incannex has finalised the development of formulation of its psilocybin drug product, PSX-001. Final preparations for the manufacture of the cGMP clinical trial supply of PSX-001 are underway. Documentation on the formulation development and cGMP manufacture will form the final pieces of the FDA IND application that Incannex commenced in August of 2023.
Incannex is continuing to work to select trial sites and prepare the relevant regulatory documents for submission to the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK.
Generalised Anxiety Disorder
Generalised Anxiety Disorder (GAD) is characterised by excessive anxiety and worry that occurs more days than not for at least 6 months, and is not restricted to any particular environmental circumstances. Symptoms are variable, including feelings of persistent and excessive worry, nervousness, restlessness, difficulty concentrating, and a range of somatic manifestations. People with GAD find it difficult to control their worry, which may cause significant distress and impairment in social, occupational, or other areas of functioning. GAD is a relatively common disorder (about 6-9% lifetime prevalence, and about 3% 12-month prevalence in countries like Australia and the United States). As with other mood disorders, successful treatment of GAD remains inadequate, with less than half of patients achieving remission following evidence-based treatment, alongside high relapse rates, and substantial treatment side-effects or cost.
Addressable Market
- Global market for GAD is predicted to reach USD $ 7.5 billion by 2023 (1)
Development
Incannex is currently undertaking a phase 2 proof of concept clinical trial assessing the safety and efficacy of its own PsiGAD psilocybin-assisted psychotherapy in 72 trial participants. The 10-week treatment program includes two dosing sessions with either psilocybin or active placebo.
The Company has had a pre-IND meeting with the US FDA to discuss its development plan. Both the written responses and the responses provided in the teleconference with the FDA were positive, constructive, and supportive of PsiGAD therapy.
The FDA has provided guidance on Inannex’s long-term development strategy with regards to what will be required for a successful NDA (FDA approval) and marketing authorisation.
Specific feedback from the FDA on the Company’s proposed clinical trial designs have played an important role in shaping the design of a planned phase 2b PsiGAD clinical trial, which will be the IND opening study, following the conclusion of the PsiGAD proof of concept trial that is currently underway.
Change to classification of psilocybin in Australia
From 1 July 2023, medicines containing psilocybin can be prescribed by specifically authorised psychiatrists for the treatment of treatment-resistant depression. This is considered by the Australian Therapeutic Goods Association (TGA) to be the only condition whereby there is sufficient evidence for potential benefits in certain patients. Incannex is assessing an application to TGA for PsiGAD therapy to be included in the authorised prescriber scheme for psilocybin.