ACADIA Pharmaceuticals (NASDAQ: ACAD) is a biopharmaceutical
company focused on innovative small molecule drugs that address unmet medical
needs in neurological and related central nervous system disorders. They are
developing pimavanserin, which is in
Phase III development as a potential first-in-class treatment for Parkinson's
disease psychosis (PDP).
Pimavanserin is a new chemical entity that can be
taken orally as a tablet once-a-day. Pimavanserin selectively blocks the
activity of the 5-HT2A receptor, a drug target that plays an important role in
psychosis.
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| www.chemnet.com |
Brief
background on Parkinson’s disease Psychosis (PDP)
Parkinson’s disease is a chronic and
progressive neurodegenerative disorder that affects about 1 million people in the United States and
from 4-6 million people worldwide.
It is the second most common neurological
disorder after Alzheimer’s disease.
Parkinson’s disease involves the death of
neurons in a region of the brain that controls movement, creating a shortage of
an important neurotransmitter known as dopamine, thereby rendering patients
unable to direct or control their movements in a normal manner.
Parkinson’s disease is characterized by well
known motor symptoms, including rest tremor, bradykinesia, rigidity, and
disturbances of balance and posture, as well as by non-motor symptoms,
including psychosis, depression, sleep disturbances, compulsive behaviors and
dementia. Among these the
onset of psychosis is considered a particularly poor prognostic sign.
Parkinson’s
disease psychosis, or PDP, is a debilitating disorder that develops in up to 60
percent of patients with Parkinson’s disease. PDP is characterized by the
presence of hallucinations and delusions.
Current standard of care is to reduce or
withdraw dopaminergic therapy. Use of antipsychotics has been drug of choice for
management of symptoms but they tend to counteract the anti-parkinson’s therapy
making the therapy even worse. The drug currenly used are Clozapine, Seroquel
(quetiapine) and Abilify (aripiprazole) but they come with very bad side effects
mainly being agranulocytosis (severely low amount of white blood cell important
for immune system and fighting infections)
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| cnsspectrums.com |
Current State of Pimavanserin
In late 2009, Pimavanserin failed to show
statistically significant result to prove its efficacy in Phase III trial for
PDP when compared to placebo. That trial did not meet its primary endpoint but the
key secondary endpoint of motoric tolerability and pimavanserin was generally
safe and well tolerated in the study.
In July 2010, they started a new Phase III
trial with new trial design. The redesigned study will include only patients
from North America, and will exclude mildly psychotic patients. The main goal of
the ongoing study is to reduce psychotic symptoms in Parkinson's disease
patients. The secondary goal is to check tolerability to the drug pimavanserin.
The study will now enhance the main goal, which Hacksell (CEO) said has already
been approved by the U.S. Food and Drug Administration. The CEO Uli
Hacksell, has repeatedly said , "We believe
pimavanserin has an ideal profile to effectively treat PDP without impairing
motor function and, therefore, provides the potential for an important advance
in therapy for patients suffering from this large unmet medical need."
The Trial
design can be viewed here (NCT01174004), “http://clinicaltrials.gov/ct2/show/NCT01174004?term=acadia&rank=3”
Reasons
why I think the Phase III (-020) trial will be successful:
- The trial will test only 40mg pimavanserin vs. placebo in a 1:1 randomization compared to 3 arms in the previous phase failed trial. It should help reduce the statistical complexity
- This trial also has two-week lead-in period which include social therapy in order to help pull initial placebo responses ahead of the assessment period. This will help rule out placebo effect
- The trial has new Scale for the Assessment of Positive Symptoms (SAPS) endpoint through analysis of the two previous trials -012 and -014. The new trial will focus on 9 items compared to 20 items in previous failed trials. The SAPS endpoint was accepted by the FDA
- Most importantly, this trial will enroll a more homogeneous patient population (US patient population ONLY). The previous failed trial enrolled patients in seven different countries (U.S., U.K., France, Bulgaria, India, Russia, and Ukraine)
In
my opinion, the stock prices should start to run as we approach August 31,
2012. According to their last quarterly result webcast they are projecting on
clinical trial completion near end of August 31, 2012. The final data will be released 3 months after that so the final data release will be November 2012. Since we have strong timeline of data
release, the stock price should go up considerably.
As we
get closer to the mid 4Q 2012 we will start to see more news around ACAD. A
recent PR was released on Reuters, http://www.reuters.com/finance/stocks/ACAD.O/key-developments/article/2573125.
I am predicting more PRs like this will make this stock very volatile.
Disclosure: May initiate position in next 72 hours
Resources: Reuters, Acadia Pharmaceutical Investor Relations, Google Images, Journal of Clinical Psychiatry, Abilify Package Insert
Only question I have is where will people point when looking at data? Failed trial or the altering of the trial design to show clinical/statistical benefit...
ReplyDeleteIn my opinion, people or retail investors usually looks at the news (ex. WSJ, Reuters, etc) for results. These newspaper reports the data very briefly so it will focus mostly on the altering of trial design. Since this trial is mostly US based population, I feel there are chances of great success.
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