On January 29, 2016, ACADIA Pharmaceuticals Inc. (NASDAQ:ACAD) reported the PDUFA date for its lead pipeline candidate, Nuplazid. Alongside the PDUFA, the company also reported the scheduling of an advisory committee meeting to review the drug and its data. The FDA doesn’t always follow the recommendation of its advisory panels, but if the panel votes to recommend approval, we’ll definitely see a spike in ACADIA’s market capitalization. With this in mind, and ahead of the panel review. Let’s take a look at the drug, and the data on which the NDA is based, in an attempt to try and preempt the panel’s opinion. Here goes.
Those familiar with the company will remember Nuplazid from the headlines it made by missing a target NDA submission date early last year – something we will touch on in a little more detail shortly. It’s a breakthrough designated oral administration therapy with a target indication of Parkinson’s disease psychosis (PDP). Not many people outside of the medical space are aware of PDP, but it’s a very common symptom of Parkinson’s, with up to 50% of Parkinson’s disease sufferers displaying signs of the condition. There’s no currently available treatment – in some cases antipsychotic SOCs are used but these have a range of unpleasant side effects due to their lack of selectivity.
Nuplazid is what’s called an inverse against. The concept of an inverse agonist is pretty complicated, but can be simplified as follows: an agonist stimulates the production of something (say, dopamine, for example) by binding to a receptor; an antagonist switches off the receptor, stopping the production; an inverse agonist binds to the receptor and actively reduces the amount of again, let’s say dopamine, in the system.
In this instance, it’s an inverse agonist of serotonin – overexpression of which is linked to psychosis in PDP patients. It binds to a receptor called 5-HT2A (which is responsible for serotonin release) and works in the way described above.
The selectivity of it means it only works to counter serotonin overexpression, so it’s side effects are practically none existent. It’s also (and this is a big one in antipsychotic therapy) abuse deterrent i.e. a patient won’t get addicted to the drug. This selectivity is its USP in the space.
How did the drug perform in trials? Well, the company trialed the drug between 2008 and 2012 across three separate phase IIIs, and in all three demonstrated efficacy through the meeting of a host of both primary and secondary endpoints. Safety and tolerability was no issue, and for the reasons just described, adverse AEs non-frequent.
So it’s a shoo in for approval? Not so fast. It may be safe and effective, but one of the major reasons for ACADIA missing its initial NDA submission target date is rooted in supply. There have been some well documented supply issues, and with such a big target indication, the FDA will need the company to prove unequivocally that it can produce and distribute a large amount of Nuplazid right off the bat on approval. And that’s likely what the review panel will focus on in the upcoming meeting.
What’s the takeaway here? ACADIA has a drug that, if approved, could be sold to up to 50% of the more than 1 million US individuals affected by Parkinson’s disease. It’s a potential blockbuster, with three successful phase IIIs backing up what looks to be a strong NDA – that is, at least from a safety and efficacy point of view. The FDA has expressed concern, however, about the company’s ability to meet demand through its own manufacturing and distribution channels, and this could be a sticking point for both the agency and its review panel over the coming few months.
Milestones? The aforementioned advisory panel review is slated for March 29, 2016, and we’ll likely get data from the review that day, or at market open on the 30th. Beyond that, PDUFA is set for May 1, 2016. Both dates have the potential to induce some great upside in ACADIA if things run smoothly – one to keep an eye on going forward.