ACOR
#Thanks, <UNK>.
Good morning, everybody.
We reported AMPYRA net sales of $131.5 million for the second quarter of 2017, that was an increase of 8% over 2016.
We are reiterating our 2017 AMPYRA revenue guidance of $535 million to $545 million.
On March 31, we announced that the U.S. district court invalidated certain of our patents related to AMPYRA.
We disagree with the ruling and filed a notice of appeal in May.
The appeals process typically takes 12 to 18 months from the notice of appeal and our opening brief is due the first week of August.
We will continue to drive the growth of AMPYRA and benefit from its revenue, at least, through July of 2018, pending the outcome of the appeal.
Moving to our late stage pipeline.
We filed our NDA for INBRIJA on schedule during the second quarter.
This was a key milestone achieved, thanks to intensive work by many dedicated Acorda associates.
We expect the FDA to notify us by the end of September, regarding whether the submission is accepted for full review and we expect the 10-month review.
INBRIJA is being developed as an on-demand therapy for symptoms of OFF periods and people with Parkinson's who are on an oral levodopa carbidopa regimen.
OFF periods are one of the most debilitating aspects of the disease.
Our commercial preparations for the launch of INBRIJA are well underway.
We also expect to submit a marketing authorization application or MAA to the European Medicines Agency by the end of 2017.
In the last month, we presented efficacy and long-term safety data from the INBRIJA Phase III program at the MDS meeting in Vancouver.
The efficacy study met its primary endpoint, an improvement in UPDRS Part III, the standard validated endpoint agreed to by the FDA.
The long-term safety data showed no statistical differences in the mean changes in FEV1 and DLco, pulmonary function test from baseline to week 52, between INBRIJA and observational control groups.
Overall, in these studies, patients were using INBRIJA an average of about twice a day up to 1 year of treatment.
We're projecting peak INBRIJA net sales in the U.S. alone of more than $500 million.
Moving to tozadenant.
Tozadenant is an oral adenosine A2a antagonist, representing a potential first-in-class treatment for chronic maintenance therapy of Parkinson's disease in the U.S. This would be complementary to INBRIJA, which is intended for on-demand use rather than chronic maintenance use in OFF periods.
In a Phase IIb trial, tozadenant reduced average daily OFF time by more than 1 hour relative to placebo, even in people already being treated with several other concurrent Parkinson's medications.
We expect results from our pivotal Phase III clinical trial in the first quarter of 2018.
We believe that tozadenant, if approved, represents a commercial opportunity in the U.S. that is greater than that of INBRIJA.
Dave will now review select financials for the quarter.
Thanks, Dave.
So in the first half of 2017, Acorda experienced a major setback, and also major positive milestones, respectively, the adverse AMPYRA patent verdict and the positive INBRIJA Phase III and safety data and timely submission of the INBRIJA NDA.
Setbacks are inherent in the growth of biopharmaceutical companies and the difference between long-term value creation and not is most often diversification and execution.
Acorda's management team and board implemented an aggressive diversification strategy, beginning 3 years ago, which is now yielding results.
Very importantly, following the reductions to our operating expenses, which we implemented after the patent verdict, we project that the company's balance sheet will be sufficient for us to achieve cash flow positivity with the launch of INBRIJA in 2018.
This does not include any consideration of additional cash to be generated by royalty monetization or other business development activities.
We're focused on 3 key areas this year and into 2018: advancing our late stage Parkinson's program toward approval and commercialization; maximizing the value of AMPYRA, including appealing the patent verdict; and generating value through business development initiatives.
We'll now take your questions.
Operator.
Okay, great.
Thanks, Mike.
So the activities between now, and hopefully, approval next year are executing, really, on the program.
So we will be hopefully engaging with FDA throughout and responding to questions, providing them with information.
There'll be the usual 120 days safety update that we'll provide.
As we said on the call or in the presentation, we expect somewhere in September ---+ by somewhere in September to be informed of, hopefully, acceptance of the NDA filing and then proceed from there with the actual review and back-and-forth with FDA.
We're preparing separately on manufacturing.
Pre-approval inspection, is a key item, and so we're drilling on that over and over and over so that we will be prepared for pre-approval inspections.
So again, it's really execution and just making sure that everybody here is focused, has their eye on the ball and that we are thinking of anything possible that FDA may come up with our may need, so that we're able to respond in a very timely and crisp way.
In terms of a panel, we certainly have not been informed that there'll be a panel and we don't know.
I don't want to front-run the FDA on this, because they will be telling us whether or not they think there's one necessary.
We, personally, don't see why there would be a panel for this particular drug with the data set that we have.
But again, we can't preempt the FDA.
We don't see a reason, but if they do, we'll discuss it with them.
And then with regards to the NeuroDerm deal that you alluded to, it's very encouraging to see that there are repeated signs now that the whole issue of OFF periods for people with Parkinson's is really gaining a lot of currency.
When we did our original deals with Civitas 3 years ago, there were a lot of people, even I have to say, even in the medical field, who were not entirely convinced or not really into it.
I think that deal really underscores that this is one of the key frontiers and key unmet needs in the Parkinson's space, and it's something that people with Parkinson's and MDS specialists are enthusiastically encouraging the industry to come up with solutions for.
So we feel we're terrifically positioned with INBRIJA on that one.
It's not that we are more optimistic, it's that our commercial team has continued to do its market research and its work in the area.
And we're at a point where we feel confident coming out and telling people that we think it's a larger opportunity based on the work that's been done.
Remember, it's a chronic maintenance therapy versus an on-demand therapy, which would be used periodically in a different rates by different patients, which would be INBRIJA.
Whereas here, you've got something where the Phase III looks like the Phase II, you have a brand-new mechanism of action, a brand-new class of drug, first time in 20 years that, that would be true in U.S. So there's a lot of cachet for that and we think that, once you put a patient on it and if it works for them, they are going to take it every single day.
So within the Parkinson's space, we would expect more broad and more chronic usage, which is why we think it's bigger.
The other thing to point out is that we originally were expecting that we would be entering a market after istradefylline, which was Lunbeck's entry.
Because of the failure of that program, we no longer are accounting for that in our market projections, and that also feeds into, obviously, a bigger market opportunity for tozadenant.
Yes, so we have studied extensively all of the drug device ---+ particularly, the inhaled drug device combinations and what the story was there.
The team at ---+ what is now Acorda Boston, but was Civitas, has been doing this for 20 years, and had an enormous amount of experience with FDA as they did the original insulin program, which delivered over 1 million doses over that program for several years.
So they've been able to fold all of that learning over that long period of time and interactions with FDA into what we've done with INBRIJA.
Let's admit right up front, we do all the work we can and the FDA may still find things, but what I ---+ what we are comforted by is that the Civitas team has checked every single box that we and every consultant that we brought in and some of them being ex-FDA as well, could think of.
Typically, when these things have had issues, if they have not been direct issues with the clinical data like safety or efficacy issues or the molecule itself, they've typically been delivery issues, reproducibility of dose from dose to dose or manufacturing issues around the device itself.
We have done a huge amount of work to mitigate that.
One of the things, with this product, that is more comforting than some others for example, is that it's not a metered-dose inhaler.
Typically, the metered-dose inhalers tend to be more complicated, right.
Because you have multiple doses in a single device.
You have to ensure that every single dose that comes out is the same every time and so on.
This is a much more simple and straightforward device that's been refined over many years.
It has, I think, 6 or 7 pieces of plastic that are molded together and one little metal piece that pierces the capsule.
But the dose is actually much more like an ordinary pill or capsule, because it is a capsule.
So you know you're getting the same amount of powder every single time because that's what's in the capsule.
You put it in the device, it pierces and then you inhale what's in the capsule.
So from that standpoint, there's just less complexity.
There are just ---+ It's like when you buy sort of a modern refrigerator with a digital display and all kinds of bells and whistles, and the one thing that you are always worried about is there more things to break, right.
Here, there are really fewer things to break.
And so that, in and of itself, gives us a lot of comfort.
That and the fact that we've just done a huge amount of homework over and over and over.
And having said that, if FDA comes up with questions about it, we will be ready.
Okay.
So they are nominally the same going after the same target, which is the adenosine 2A ---+ A2a receptor.
Istradefylline is a different class of molecule.
It's a xanthine versus an adenosine based molecule, which is tozadenant.
Now having said that, that doesn't give you the answer, but it does tell you that they are very different types of molecule.
What we were attracted to when we made the decision to buy Biotie Therapies with tozadenant, was that when we looked at the history of data in the field, the Phase IIb trial for toz, we believe, had more robust data than the istradefylline trials had.
So the outcome measures were stronger, there was more internal consistency.
There was clear dose responsiveness.
It was an extremely robust Phase II.
Istradefylline was quite variable when you looked at the data.
So there were certainly signals there, but in our view, it was not nearly as convincing and strong as tozadenant.
So we start out with that as a baseline.
If you look at the Phase II data, we come out and our external experts come out concluding that it worked in Phase II.
And then the issue is, how do you translate that reliably into a larger Phase III study, so that you get, at least, the same result that you did in Phase II.
And that's been an area of difficulty for this class of drug and that was seen with preladenant, which was the Merck entrant into the field.
So we took learnings from the preladenant study, there was a paper in JAMA that was published after their Phase III failed, pointing to very clear steps that were missteps that occurred during that trial, which we have taken into account in our trial.
So for example, there were entire countries where they decided to put centers that did not work out well, that did not have high-quality data.
We avoided those countries.
We made sure that we vetted the centers that were doing the trials extremely, so that we only had the highest quality centers that had a track record of producing high-quality data.
We have an external group of expert movement disorder consultants, specialists, some of the most accomplished in the field, who actually reviewed the recruitment in this study, and that's probably the secret sauce that goes along with this.
So they actually are reviewing the recruitment to make sure, in an ongoing way, that the patients that are coming into the study are actually the right patients, and if they conform to the inclusion-exclusion criteria, with no exceptions.
That's also been an issue for other trials where, frankly, it's gotten sloppy and it just wasn't picked up and they did have the right patient population.
We have ongoing monitoring of the trial.
We look at the blinded data that's coming in just to make sure that there is nothing [on tour] that looks weird or funny going on.
When something comes up that sounds like it might be an issue with the center, we have a SWAT team that goes out and that immediately engages with the center.
So we're doing everything that we can think of and that our external experts can think of to ensure that the trial will have the highest possible quality data.
Our belief is that, for other members of the class that have not done well in Phase III, that these were the reasons why they did not do well.
And so we're mitigating those risks.
Yes, so it's very much alive.
We didn't emphasize it on the call because we wanted to emphasize the near-term late stage products.
But in fact, we have of a number of drug in the pipeline that are going to have read-outs this year, SYN120 prominent among them for symptoms of dementia in Parkinson's disease.
Just to remind people, this is a combined 5-HT2A/5-HT6 antagonist.
5-HT6 has been implicated in cognitive symptoms.
5-HT2A is more on the affective side where you would be looking at symptoms of psychosis.
And you find ---+ if you look at the field, you've got pimavanserin from Acadia that's really primarily 5-HT2A, that's already been approved for psychotic symptoms in people with Parkinson's, you've got Axovant working and others working on 5-HT6 angle for dementia, mostly in Alzheimer's and other dementia ambitions.
So we're actually quite excited by the potential of SYN120.
This is the first real human proof of concept trial for this particular molecule in Parkinson's with dementia.
We should have a read out by the end of the year.
Now ---+ yes, the caveat on it is that the trial is, somewhat, underpowered.
We inherited that when we bought Biotie.
They did not have the funding to do tozadenant properly and to do a larger SYN120 trial.
So they did the best they could with the funding available.
Nevertheless, we hope we'll see some useful data and if we see positive signals that are credible out of this study, we would have another molecule that we can launch into late stage development, that would be extremely exciting.
Plus the potential that it could actually be used as a dual mechanism, because people with these degenerative brain conditions, Parkinson's, Alzheimer's, others.
Typically, there are a lot of them, who suffer from both cognitive symptoms and psychotic symptoms.
And this would offer the potential of having a single treatment that could address both.
So we're excited about it.
But we have to wait for the data at the end of the year.
And then of course, we're still waiting for data, also, by the end of the year on our M22 antibody for remyelination in MS, and also on our molecule for our VAP-1 inhibitor for primary sclerosing cholangitis, which is a proof of concept.
It's a potent anti-inflammatory molecule with potentially multiple indications.
This is a proof of concept.
If this looks interesting, we would look at it for perhaps ---+ or it could be looked at for things as diverse as liver fibrosis, for example.
So all of that should be reading out by the end of the year and we'll see where we are.
It's an excellent question and I'm not sure I have the full answer for you.
I will tell you that when you are dealing with symptomatic relief, typically, these indications have a lot more in common physiologically than not.
If you are dealing with disease modification, you're in a different mode, right.
Because then you are addressing different disease substrates.
But when you are getting into the substrates of cognitive dysfunction in dementia, so for example, by boosting cholinergic output, those have more in common than not across these different conditions.
So we would expect that if you see a positive signal in Parkinson's, that, that ought to translate into something like Alzheimer's disease.
All right.
Well, thank you very much for joining us, and we are looking forward to some exciting developments over the next 6 to 12 months and we'll see you at the next quarter call.
