Pimavanserin Demonstrates Highly Significant Antipsychotic Efficacyand Maintenance of Motor Control in Parkinson’s Patients
Significant Improvements Also Observed in All Secondary andExploratory Measures
Conference Call and Webcast to Be Held Today,
“These data represent an unprecedented advance for Parkinson’s patientswho suffer from the psychosis frequently associated with this disease,”said
Primary Endpoint
The primary endpoint of the trial was antipsychotic efficacy as measuredusing the SAPS-PD, a 9-item scale adapted from the hallucinations anddelusions domains of the Scale for the Assessment of Positive Symptoms,by comparing the mean change from baseline to day 43 for pimavanserinversus placebo. SAPS-PD assessments were performed by blinded,independent centralized raters. The pimavanserin arm demonstrated arobust 5.79 point improvement in psychosis at day 43 compared to a 2.73point improvement for placebo, representing a highly significant andclinically meaningful treatment difference of 3.06 points on SAPS-PD(p=0.001).
| Baseline Mean | Mean Change at Day 43 | ||||||||||||||||||||||||
| PBO | PIM | PBO | PIM | P-value | |||||||||||||||||||||
| (n=90) | (n=95) | ||||||||||||||||||||||||
| SAPS-PD | 14.73 | 15.88 | -2.73 | -5.79 | 0.001 | ||||||||||||||||||||
Note: mixed model repeated measures (MMRM) method was applied in theprimary analysis of the intent-to-treat (ITT) population. Thesignificance test was based on least-square mean change from baselinefor each arm using a 2-sided beta = 0.05.
Key Secondary Endpoint
The key secondary endpoint of the trial evaluated motoric tolerabilityand functional outcome using Parts II and III of the UPDRS. Theobjective of this secondary endpoint was to demonstrate thatpimavanserin could achieve its antipsychotic effects without worseningmotor function as compared to placebo in PDP patients. A pre-specified,non-inferiority analysis was used to compare the mean change frombaseline to day 43 for pimavanserin versus placebo using a two-sided 95percent confidence interval (CI) for the treatment difference. Motoricimprovements were seen in both the pimavanserin and placebo arms and theCI associated with the treatment difference did not exceed apre-specified margin of 5 points for clinically relevant change,confirming that pimavanserin met this key secondary endpoint and did notworsen motor function in PDP patients.
Secondary and Exploratory Efficacy Measures
The secondary efficacy measure in the trial was an assessment ofclinical global improvement by the investigator using the CGI-I scale.Pimavanserin demonstrated a highly significant improvement on thismeasure (p=0.001), further supporting its antipsychotic efficacy.
In addition, other clinical benefits of pimavanserin were observed inexploratory efficacy measures of sleep and caregiver burden. Sleep wasassessed using the SCOPA-sleep scale, which was designed to enable theinvestigator to evaluate nighttime sleep and daytime wakefulness inParkinson’s patients. Pimavanserin demonstrated significant improvementson both nighttime sleep (p=0.045) and daytime wakefulness (p=0.012) onSCOPA.
Caregiver burden was assessed using the Caregiver Burden Scale. Thisscale was completed by the caregiver to provide a quantitativeassessment of burden associated with the patient’s functional/behavioralimpairments, the circumstances of at-home care, as well as thecaregiver’s health, social life and interpersonal relations.Pimavanserin demonstrated a highly significant improvement on theCaregiver Burden Scale (p=0.002).
Safety and Tolerability Profile
Consistent with previous studies, pimavanserin was safe and welltolerated in this trial. Based on a preliminary analysis of safety data,the most common adverse events were urinary tract infection (11.7% PBOvs. 13.5% PIM) and falls (8.5% PBO vs. 10.6% PIM). Adverse events weregenerally characterized as mild to moderate in nature. The only seriousadverse events that occurred in more than one patient were urinary tractinfection (1-PBO vs. 3-PIM) and psychotic disorder (0-PBO vs. 2-PIM).Ninety percent of the patients who completed the clinical phase of thistrial elected to roll over into the ongoing open-label safety extensionstudy. Patients were only eligible to participate in the extension studyif the treating investigator also deemed them to be likely to benefitfrom continued treatment with pimavanserin.
“We are excited with the results of this study which demonstrate thatpimavanserin has the potential to offer PDP patients a new treatmentoption that, for the first time, can achieve the desired clinicalprofile by providing an effective, safe and well tolerated antipsychotictherapy,” said Uli Hacksell, Ph.D., Chief Executive Officer of ACADIA.“We remain committed to advancing pimavanserin to registration as afirst-in-class treatment for this large unmet medical need. Theseresults also suggest that pimavanserin may have the ideal clinicalprofile to address a broader range of neuropsychiatric disorders thatare underserved by currently marketed antipsychotics.”
“These significant and consistent top-line results are a strongvalidation of the optimized study design used in this trial,” said
About the Trial Design
The pivotal Phase III trial, referred to as the -020 Study, was amulti-center, double-blind, placebo-controlled study designed toevaluate the efficacy, tolerability and safety of pimavanserin as atreatment for patients with PDP. A total of 199 patients were enrolledin the study and randomized on a one-to-one basis to receive either 40mg of pimavanserin or placebo once-daily for six weeks, following atwo-week screening period including brief psycho-social therapy.Patients also received stable doses of their existing anti-Parkinson’stherapy throughout the study. The primary endpoint of the -020 Study wasantipsychotic efficacy as measured using the “SAPS–PD” scale, whichconsists of nine items from the hallucinations and delusions domains ofthe Scale for the Assessment of Positive Symptoms, or SAPS. These nineitems have been shown to be particularly relevant to the expression ofpsychotic symptoms in patients with Parkinson’s disease and to have highinter-rater reliability for assessment of severity. Motoric tolerabilitywas a key secondary endpoint in the study and was measured using PartsII and III of the Unified Parkinson’s Disease Rating Scale, or UPDRS.
Conference Call and Webcast Information
ACADIA will host a conference call and webcast with slides today,
About Pimavanserin
Pimavanserin is ACADIA’s proprietary small molecule that actsselectively as an antagonist/inverse agonist on serotonin 5-HT2Areceptors and is in Phase III development as a potential first-in-classtreatment for Parkinson’s disease psychosis. Pimavanserin can be takenorally as a tablet once-a-day. ACADIA discovered pimavanserin and holdsworldwide rights to this new chemical entity.
About Parkinson’s Disease Psychosis
According to the National Parkinson’s Foundation, about one millionpeople in
About ACADIA Pharmaceuticals
ACADIA is a biopharmaceutical company focused on innovative treatmentsthat address unmet medical needs in neurological and related centralnervous system disorders. ACADIA has a pipeline of product candidatesled by pimavanserin, which is in Phase III development as a potentialfirst-in-class treatment for Parkinson's disease psychosis. ACADIA alsohas clinical-stage programs for chronic pain and glaucoma incollaboration with
Forward-Looking Statements
Statements in this press release that are not strictly historical innature are forward-looking statements. These statements include but arenot limited to statements related to the progress and timing of ACADIA’sdrug discovery and development programs, either alone or with a partner,including the commencement or progress of clinical trials and theresults of clinical trials, and the clinical benefits to be derived fromACADIA’s product candidates, in each case including pimavanserin. Inparticular, forward-looking statements include statements regarding thepotential implications of the results of the -020 study; the potentialfor selective, non-dopaminergic-based therapy, such as pimavanserin, totransform the treatment landscape for patients with PDP; the potentialof pimavanserin as a first-in-class, effective, safe and well toleratedantipsychotic therapy and treatment for PDP; and the possibility thatpimavanserin may have a clinical profile suitable to address a broaderrange of neuropsychiatric disorders that are underserved by currentlymarketed antipsychotics. These statements are only predictions based oncurrent information and expectations and involve a number of risks anduncertainties. Actual events or results may differ materially from thoseprojected in any of such statements due to various factors, includingthe risks and uncertainties inherent in drug discovery, development,regulatory review and commercialization, and in collaborations withothers, and the fact that past results of clinical trials may not beindicative of future trial results. For a discussion of these and otherfactors, please refer to ACADIA’s annual report on Form 10-K for theyear ended December 31, 2011 as well as ACADIA’s subsequent filings withthe
Source:
Investor Contacts:
ACADIA Pharmaceuticals Inc.
UliHacksell, Ph.D., Chief Executive Officer
Thomas H. Aasen,Executive Vice President,
Chief Financial Officer and ChiefBusiness Officer
(858) 558-2871
or
MediaContact:
Russo Partners
David Schull
(212)845-4271 or (858) 717-2310
david.schull@russopartnersllc.com