dm+d

Unassigned

New Medicines

NuplazidDementia-associated psychosis

Information

Nuplazid
Licence extension / variation
Acadia
Acadia

Development and Regulatory status

Phase II Clinical Trials
Phase II Clinical Trials
Not recommended for approval (Negative opinion)
Jun 22Ahead of an FDA advisory committee meeting to discuss Nuplazid for treating hallucinations and delusions associated with Alzheimer ’s disease psychosis, FDA staff point out that Nuplazid ’s benefit in a PIII trial for a broader psychosis population was actually driven by the Parkinson ’s disease subgroup. Previously, Acadia said Nuplazid in the AD subgroup in the PIII Harmony study was not statistically significant because of the trial design. The FDA is now saying there is more of a problem than just statistical powering. Despite Acadia ’s argument that Nuplazid showed consistent benefit, the FDA says the AD and PD subgroups appeared to respond differently to Nuplazid [19]
Jun 22FDA advisory committee vote 9 to 3 that pimavanserin does not appear to be effective in Alzheimer’s psychosis [20].
Mar 22Acadia announce it has received a target action date of Aug 4, 2022 from the U.S. FDA for its resubmitted sNDA [18].
Feb 22Acadia Pharmaceuticals announces resubmission of sNDA to FDA for pimavanserin to treat Alzheimer´s disease psychosis. Resubmission includes additional analyses from HARMONY1 trial & Study 0192, intended to address issues raised by FDA previously [17].
Dec 21Acadia plans to resubmit its application for pimavanserin, to treat hallucinations and delusions associated with dementia, homing in specifically on patients with Alzheimer’s disease psychosis (ADP), to the FDA in Q1 2022 [16].
Aug 21Acadia announces it completed a Type A end of review meeting regarding the FDA complete response letter (CRL) for the sNDA for pimavanserin for the treatment of hallucinations and delusions associated with DRP. The FDA reiterated their stated position in the CRL, that pimavanserin should be studied by individual subgroups of dementia, and advised that the best path forward is to conduct an additional clinical study in each of the subgroups for which Acadia seeks approval. However, the FDA also indicated that they are open to having another meeting to discuss additional analyses from the HARMONY and -019 studies in support of a potential resubmission without an additional clinical study [15].
Mar 21Acadia announce they have received notification from the US FDA stating that the agency has identified deficiencies that preclude discussion of labeling and post-marketing requirements/commitments at this time. The company plans to work with the FDA to learn the nature of the deficiencies and seek to resolve them. It is not clear whether the agreed PDUFA action date of April 3 2021 will now be met [13].
Jul 20US FDA accept sNDA for pimavanserin to treat dementia patients with hallucinations and delusions; a decision is expected 3/4/21 [12].
Sep 19Acadia plan to meet with FDA in 2020 regarding submission of a sNDA [10].
Oct 17US FDA grants Breakthrough Therapy Designation to pimavanserin for dementia-related psychosis [6].

Category

Selective 5-HT2A inverse agonist
Behavioural signs, such as aggression, psychomotor agitation and psychosis (hallucinations and delusions), are very common in patients with Alzheimers disease, especially in the late stages of the disease [2]
Dementia-associated psychosis
Oral

Trial or other data

Jul 21PIII HARMONY RCT (n=351) was stopped early for efficacy, patients who had response to treatment (n=217) had lower risk of relapse with continuation of drug than with discontinuation (13% vs. 28%, placebo; HR 0.35; 95% CI, 0.17 to 0.73; p=0.005) [14].
Dec 19In PIII HARMONY study (n=392) patients had average baseline of moderate to severe psychosis as per Scale for Assessment of Positive Symptoms-Hallucinations and Delusions (SAPS-H+D). Nuplazid patients saw their SAPS-H+D score improve by 63% and 75.2%, respectively [11].
Sep 19ACADIA Pharmaceuticals announce PIII Harmony study meets primary endpoints. Results from a planned interim analysis reported a statistically significant longer time to relapse of psychosis with pimavanserin vs placebo resulting in an early halt of the trial [9].
Nov 18PIII HARMONY trial (NCT03325556) is still recruiting patients in the US; timescales unchanged [8].
Dec 17PIII HARMONY trial (NCT03325556) is recruiting patients in the US. Collection of primary outcome data due to complete Mar 2020 [7].
Oct 17PIII HARMONY trial to evaluate the efficacy and safety of pimavanserin for treatment of hallucinations and delusions associated with dementia-related psychosis starts. The trial will be conducted globally and will enrol approximately 360 patients. Primary endpoint is time to relapse in the double-blind period. ACADIA believes that positive results from one PIII study together with supportive data from prior studies could serve as the basis of a supplementary New Drug Application [6].
Dec 16a further PII trial is in progress in the US (NCT02992132) assessing efficacy in treatment of agitation and aggression in patients with AD; estimated enrolment is 432 and estimated primary completion date June 2019 [5].
Dec 16Acadia announce positive top-line results from PII trial (NCT02035553) - at six weeks, the primary outcome (Neuropsychiatric Inventory - Nursing Home Version, NPI-NH) score was statistically significantly better in the pimavanserin group vs. the placebo group (3.76 point improvement from baseline vs. 1.93 points for placebo; p=0.0451). In the secondary outcome of scores at 12 weeks, the improvement was maintained in the treatment group but the difference did not statistically separate from placebo [4].
Dec 15Remains in PII development currently [3]
Nov 13Phase II feasibility trial initiated to examine the efficacy and safety of pimavanserin as a treatment for patients with Alzheimer’s disease psychosis (ADP) [1]

NuplazidSchizophrenia, predominant negative symptoms - adjunctive treatment

Information

Nuplazid
Licence extension / variation
Acadia
Acadia

Development and Regulatory status

None
Phase III Clinical Trials
Phase II Clinical Trials

Category

Selective serotonin 5HT2A agonist
Schizophrenia affects around 1 in every 100 people over the course of their life [2].
Schizophrenia, predominant negative symptoms - adjunctive treatment
Oral