Welcome to your weekly digest of approaching regulatory and clinical readouts. Phase II data on ACADIA's (NASDAQ:ACAD) Nuplazid – the group’s only marketed drug – in Alzheimer’s disease psychosis are expected by the end of the year. The drug had a tortuous development path, but has cornered the Parkinson’s psychosis space for now, and positive results in the bigger Alzheimer’s indication might see a partner sit up and take notice.
Meanwhile, in the new year La Jolla Pharmaceutical (NASDAQ:LJPC) expects data from its lead molecule, LJPC-501, from the pivotal ATHOS 3 study testing it in catecholamine-resistant hypotension. With the company's first 27 years being short on clinical successes it will hope that LJPC-501 can turn its fortunes around.
Acadia’s phase II trial tests Nuplazid, known generically as pimavanserin, given as two 20mg tablets once daily for 12 weeks, against placebo. The study recruited 181 patients aged 50 or older who had psychotic symptoms that developed after diagnosis of Alzheimer’s.
The primary endpoint is the neuropsychiatric inventory (nursing home version), which involves interviewing professional caregivers to characterize a patient’s neuropsychiatric symptoms and psychopathology.
Nuplazid was approved in April for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis (PDP). The label includes a black box warning of increased risk of death in elderly patients with dementia-related psychosis.
Development was far from straightforward, and it took three attempts and a refinement of endpoints to get positive clinical results (Event – Nuplazid could finally give Acadia something to smile about, February 17, 2016). But with a lack of alternatives, Nuplazid has the PDP market to itself for now; only a handful of generic antipsychotics are used to treat PDP, and these suffer from disappointing efficacy and poor side-effect profiles.
According to consensus forecasts from EvaluatePharma, 2022 Nuplazid sales are expected to reach a substantial $1.2bn. ACADIA had $412m in the bank at the end of June, and completed a $230m secondary offering in August. Expansion into bigger indications such as Alzheimer’s might need the added muscle of a partner, and ACADIA will be hoping the latest results get it on potential collaborators’ radars.
La Jolla’s ATHOS 3 study tests LJPC-501 in treating acute episodes of hypotension that are unresponsive to catecholamines.
These dangerous falls in blood pressure can occur in patients with serious infections or as a result of trauma, and are often fatal if patients do not respond to vasopressin or catecholamines such as adrenaline. Meanwhile, patients who have to receive high doses of catecholamines to maintain blood pressure experience cardiac and other toxicities, which can often contribute to a high mortality rate.
The phase III trial is to enroll 315 of these patients, who will receive either LJPC-501 or placebo on top of standard-of-care vasopressors, with treatment administered by continuous IV infusion for up to seven days. Response will be evaluated in terms of change of mean arterial pressure at three hours after the start of dosing.
Although the primary endpoint is evaluated quickly, patients are followed up for 28 days to assess secondary endpoints, which include change in the cardiovascular sequential organ failure assessment score.
La Jolla’s confidence in the study stems from the fact that LJPC-501 is a proprietary formulation of angiotensin II, a naturally occurring regulator of blood pressure that is, of course, the target for anti-hypertensive agents. The study is also extremely well-powered to show success, as its size was determined by the need to have sufficient patient exposures to establish safety rather than just proving efficacy.
An earlier pilot study in 20 patients with catecholamine-resistant hypotension showed that 80% of those treated with LJPC-501 experienced a rise in blood pressure compared with 10-20% for placebo. The study met its primary endpoint, with a lower norepinephrine dose required with LJPC-0501 than with placebo.