There is not an FDA approved drug for Agitation in Alzheimer's disease. This unmet need has seen an increase in clinical trials recently. Below are a few companies that are either in, or entering into a clinical trial for agitation in Alzheimer's Disease with various drug candidates.
AVP-786
Avanir (owned by Otsuka) is running two phase 3 clinical trials for the treatment of agitation in patients with dementia of the Alzheimer's type NCT02442765, NCT02442778.
In a phase 2 clinical trial with the primary endpoint being the NPI Agitation / Aggression Domain, a stastistically significant (p=.001) was achieved with the non-deuterated version of called AVP-923. The results and publication of that trial is here Avanir JAMA Publication. The drug was generally well tolerated. The current clinical trials will complete July 2018. In four years from the beginning of 2016, AVP-786 could be the first FDA approved drug for this indication, and reach commercialization in 2020. The patent extends until 2030 in the U.S., and 2028 in the EU.
AXS-05
Owned by Axsome Therapeutics, is a combination of Dextromethorphan / Buproprion.
The company expects to enter a clinical phase 2/3 trial in 2016.
7-21-17: Axsome has now entered into a Phase 2/3 Dementia via Agitation with potential readout first half of 2020.
AVP-786
Avanir (owned by Otsuka) is running two phase 3 clinical trials for the treatment of agitation in patients with dementia of the Alzheimer's type NCT02442765, NCT02442778.
In a phase 2 clinical trial with the primary endpoint being the NPI Agitation / Aggression Domain, a stastistically significant (p=.001) was achieved with the non-deuterated version of called AVP-923. The results and publication of that trial is here Avanir JAMA Publication. The drug was generally well tolerated. The current clinical trials will complete July 2018. In four years from the beginning of 2016, AVP-786 could be the first FDA approved drug for this indication, and reach commercialization in 2020. The patent extends until 2030 in the U.S., and 2028 in the EU.
AXS-05
Owned by Axsome Therapeutics, is a combination of Dextromethorphan / Buproprion.
The company expects to enter a clinical phase 2/3 trial in 2016.
7-21-17: Axsome has now entered into a Phase 2/3 Dementia via Agitation with potential readout first half of 2020.
4-27-20: Results of phase 2/3, CMAI p=0.010
Brexpiprazole
Owned by Otsuka, with a revenue sharing agreement with Lundbeck. There are two phase 3 clinical trials for patients with agitation associated with dementia of the Alzheimer's type currently running NCT01862640, NCT01922258, with a completion date of around June 2017. This drug could prove effective for this indication, but the drug, like it's predecessor Abilify, has a black box label. Also, Otsuka chose to buy drug AVP-786 (via Avanir acquisition) for this indication, while two clinical trials with Brexpiprazole were over a year into progress.
1-9-2017: Both clinical trials are now active, but not recruiting participants. There will be 12 weeks plus a 30 day follow-up period. Participants that have completed the 12 weeks double blind trial, are eligible to enroll in a 2 month observational study.
6-7-2018: Otsuka is taking another try with Brexpiprazole with this US only clinical trial to complete in December of 2020 NCT03548584.
Lexapro (Escitalopram)
First studied by the University Rochester School of Medicine. The FDA put a dose limit of 20mg per day into the study. The clinical trial is here NCT00898807. The phase 2 Lexapro results is here Lexapro Trial. An important quote from the article relates to "cognitive worsening and QT interval prolongation observed in the Celexa (citalopram) group raised concern about the 30 mg per day dose of used in this study and may limit the clinical utility of the findings."
4-17-2017: This phase 3 clinical trial with 15mg Lexapro (escitalopram) is being sponsored by John Hopkins School of Public Health (JHSPH) for patients with agitation associated with Alzheimer's disease. The clinical trial is here NCT03108846, and has a completion date of August 2022. This is the first of potentially two phase 3 clinical trials that may be required by the FDA prior to filing an NDA if the drug is effective.
ITI-007
Intra-Cellular Therapies is planning on a phase two clinical trial in the first half of 2016 with ITI-007. The company does not have any significant findings with the drug for this indication in prior clinical trials. ITCI ran a phase 1/2 clinical trial primarily for cognition, as there were no patients that exhibited agitation at baseline. The press release is here Intra-Cellular.
6-28-16: Intra-Cellular has now entered into a phase 3 clinical trial for Alzheimer's patients experiencing agitation here NCT02817906 with readout August 2018. Terminated study.
Pimavanserin
12-12-2016: Acadia has now entered into a phase 2 clinical trial for Alzheimer's patients experiencing agitation with their 5HT2A Pima here NCT02992132, with readout June 2019.
12-20-2016: ACAD releases top-line phase 2 ADP data. But does not break out the sub-category of the primary endpoint NPI-NH, such as agitation and aggression. The company announced in their conference call, that agitation and aggression was no different than placebo group.
Bottom Line Update 12-21-2019: AXS-05 and Escitalopram, are the two drugs that hold the most promise for their respective clinical trial for Alzheimer's Agitation. AXS-05 should have phase 2/3 readout in the first half of 2020, and Escitalopram in 2022. Thank you for reading.
Brexpiprazole
Owned by Otsuka, with a revenue sharing agreement with Lundbeck. There are two phase 3 clinical trials for patients with agitation associated with dementia of the Alzheimer's type currently running NCT01862640, NCT01922258, with a completion date of around June 2017. This drug could prove effective for this indication, but the drug, like it's predecessor Abilify, has a black box label. Also, Otsuka chose to buy drug AVP-786 (via Avanir acquisition) for this indication, while two clinical trials with Brexpiprazole were over a year into progress.
1-9-2017: Both clinical trials are now active, but not recruiting participants. There will be 12 weeks plus a 30 day follow-up period. Participants that have completed the 12 weeks double blind trial, are eligible to enroll in a 2 month observational study.
6-7-2018: Otsuka is taking another try with Brexpiprazole with this US only clinical trial to complete in December of 2020 NCT03548584.
Lexapro (Escitalopram)
First studied by the University Rochester School of Medicine. The FDA put a dose limit of 20mg per day into the study. The clinical trial is here NCT00898807. The phase 2 Lexapro results is here Lexapro Trial. An important quote from the article relates to "cognitive worsening and QT interval prolongation observed in the Celexa (citalopram) group raised concern about the 30 mg per day dose of used in this study and may limit the clinical utility of the findings."
4-17-2017: This phase 3 clinical trial with 15mg Lexapro (escitalopram) is being sponsored by John Hopkins School of Public Health (JHSPH) for patients with agitation associated with Alzheimer's disease. The clinical trial is here NCT03108846, and has a completion date of August 2022. This is the first of potentially two phase 3 clinical trials that may be required by the FDA prior to filing an NDA if the drug is effective.
ITI-007
Intra-Cellular Therapies is planning on a phase two clinical trial in the first half of 2016 with ITI-007. The company does not have any significant findings with the drug for this indication in prior clinical trials. ITCI ran a phase 1/2 clinical trial primarily for cognition, as there were no patients that exhibited agitation at baseline. The press release is here Intra-Cellular.
6-28-16: Intra-Cellular has now entered into a phase 3 clinical trial for Alzheimer's patients experiencing agitation here NCT02817906 with readout August 2018. Terminated study.
Pimavanserin
12-12-2016: Acadia has now entered into a phase 2 clinical trial for Alzheimer's patients experiencing agitation with their 5HT2A Pima here NCT02992132, with readout June 2019.
12-20-2016: ACAD releases top-line phase 2 ADP data. But does not break out the sub-category of the primary endpoint NPI-NH, such as agitation and aggression. The company announced in their conference call, that agitation and aggression was no different than placebo group.
Bottom Line Update 12-21-2019: AXS-05 and Escitalopram, are the two drugs that hold the most promise for their respective clinical trial for Alzheimer's Agitation. AXS-05 should have phase 2/3 readout in the first half of 2020, and Escitalopram in 2022. Thank you for reading.
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