ABBV
#Thank you, Rick
In order to allow time for our strategic update, I'll keep my prepared remarks brief, highlighting just a few of the noteworthy milestones from the quarter
As Rick mentioned, we've continued to make significant progress across our pipeline
In immunology, we reported results from several mid and late-stage trials
Just yesterday, we announced positive top line results from three Phase III studies evaluating risankizumab in psoriasis
Data from these trials demonstrated superior skin clearance with risankizumab treatment versus two leading biologics, Stelara and HUMIRA
In the ultIMMa-1 and ultIMMa-2 trials, 75% of patients receiving risankizumab in both studies achieved PASI 90 compared to 42% and 48% of patients receiving Stelara, respectively
We are particularly encouraged by the durable rates of skin clearance demonstrated in these two studies
At one year, roughly twice as many patients treated with risankizumab achieved full skin clearance compared to Stelara, with 56% and 60% of the risankizumab patients achieving PASI 100 in ultIMMa-1 and ultIMMa-2 respectively
We also saw very high rates of efficacy in the IMMvent study, with risankizumab demonstrating superior rates of skin clearance compared to HUMIRA
Within this trial, we designed a portion of the study to evaluate risankizumab's efficacy in patients who had an inadequate response to HUMIRA
In this portion of the study, patients with an inadequate response to HUMIRA after 16 weeks were re-randomized to risankizumab or HUMIRA
And, of these patients, 66% treated with risankizumab achieved PASI 90, compared to 21% who continued with HUMIRA, demonstrating risankizumab's potential in the growing TNF inadequate responder population
We look forward to seeing data next year from the remaining trial in the psoriasis pivotal program
Our regulatory submission is on track for 2018, with commercialization expected in 2019. Moving now to upadacitinib, our oral selective JAK1 inhibitor, in development for six indications
Last month we announced top line results from the second of our Phase III studies, the SELECT-BEYOND study
In this trial, which evaluated patients who did not respond adequately or were intolerant to biologic DMARDs, both doses of upadacitinib met all primary and ranked secondary endpoints at week 12 and patient-sustained clinical response through week 24. Upadacitinib drove very high levels of response at ACR20. But more importantly, it drove strong levels of response on more stringent clinical endpoints, such as ACR50, ACR70, low disease activity, and DAS remission
We saw levels of efficacy in this difficult-to-treat refractory population, similar to efficacy more typically observed in bio-naive patients
We are aware that there continues to be significant investor interest regarding the topic of DVT and PE event rates
As we stated on our last earnings call, we have a comprehensive monitoring program in place for upadacitinib and have not observed anything in our Phase III program that we consider a signal, and the rate of DVT and PE across the program is consistent with the expected background rate in an RA population
While we can appreciate the desire to characterize event rates for upadacitinib, it is important to keep in mind that estimates based on individual events or a subset of trials have the potential to be inaccurate and misleading
The upadacitinib program is designed to provide a comprehensive safety database with more than 3,000 upadacitinib-treated patients
Evaluation of unblinded event rates and comparisons to rates in control groups and expected background rates must be done in the context of our overall program once the core studies have read out
Given the fact that we have reported data from two of our six registrational trials and that the majority of our database remains blinded, we view any attempt to calculate event rates or compare rates across upadacitinib and control groups as premature at the present time
Furthermore, providing unblinded data from ongoing studies could impact the integrity of these trials, which is something that we obviously cannot and will not do
In addition to our internal safety monitoring program, we have an independent data monitoring committee, or DMC, in place for upadacitinib in order to ensure patient safety
The DMC has access to all data from the program, including unblinded data, and monitors it for safety on an ongoing basis
The DMC is also obviously aware of the heightened interest in DVTs and PEs in this setting and has consistently made the recommendation to proceed with the program without modification
We remain very confident in upadacitinib and are investing in and advancing multiple indications in a manner that is consistent with our confidence
We also recently reported positive top line results from the upadacitinib Phase II study in atopic dermatitis, demonstrating very strong efficacy across all doses compared to placebo
In the trial, we saw very rapid response times, with upadacitinib demonstrating reduction in pruritus within the first week and improvement in skin lesions within the first two weeks for all doses
Roughly half of patients achieved a 90% or greater improvement in skin lesions by week 16. Based on these data, we plan to advance upadacitinib into Phase III studies in atopic dermatitis in the first half of 2018. Moving now to oncology, in the third quarter, we reported that the DMC for the Phase III MURANO trial recommended we unblind the study for efficacy, indicating that VENCLEXTA in combination with RITUXAN met the primary endpoint of the study of demonstrating significantly prolonged progression-free survival in patients with relapsed/refractory CLL compared to a combination of bendamustine and RITUXAN, a standard regimen in this patient population
We plan to present detailed findings from the trial at an upcoming medical meeting, and the data will support our regulatory application for broader use in the relapsed/refractory CLL population
Also in the third quarter, we received regulatory approval for the use of IMBRUVICA in chronic graft-versus-host disease after failure of one or more lines of systemic therapy
And before the end of the year we expect data from an interim analysis of the SHINE study in front-line mantle cell lymphoma, which if successful would support a label update for IMBRUVICA in this indication
We continue to make good progress with our solid tumor efforts as well, where we currently have more than 20 solid tumor assets in the clinic, 17 of which are in Phase I studies
We have started seeing early data from several of these programs, and we look forward to many more readouts as data mature over the next 12 to 18 months
At ESMO last month, we presented early data from the Rova-T BASKET study in neuroendocrine tumors
While the data are very early, we are encouraged by the findings, which showed reduction in tumor burden and confirmed responses in solid tumors beyond small cell lung cancer
Our Phase III Rova-T studies in small-cell lung cancer continue to progress, with the TAHOE study in the second-line setting and the MERU study in the front-line setting both now well underway
TRINITY, our registrational study in third-line or greater small-cell lung cancer, also continues to progress well
As we prepare for our forthcoming regulatory submissions, we've been actively engaged in discussions with regulators
We recently received feedback from the FDA that they would like to see six-month durability data as part of our regulatory submission data package
This request is not unusual in development programs where single-arm studies are being used to support approval
We anticipate that six-month data will be available in the second quarter of 2018. Therefore, we have moved the final analysis for the TRINITY study to the second quarter of next year in order to meet the FDA's request
We continue to expect our regulatory submission to follow shortly thereafter
In the area of virology, early in the third quarter, we received regulatory approvals in the U.S
, Europe, and Japan for MAVYRET
And in the area of women's health, we submitted our regulatory application for elagolix as a treatment for women suffering from endometriosis-associated pain
And this morning, we announced that we received a Priority Review designation from the FDA
While 2017 to date has already been a very eventful and productive year, we anticipate seeing several additional clinical development milestones in the coming months, and 2018 will also be a milestone-filled year
With that, I'll turn the call over to Bill for additional comments on our third quarter performance
So on upadacitinib, what we've said is that we monitor the program very carefully, and we look at the aggregate data
And so when we monitor the data at this stage, we're looking in a blinded manner across our entire database
And it's important to understand that because I can't give you a rate that is a upadacitinib rate today without talking about unblinded data and ongoing studies, and I can't do that
So what I'll do is I'll talk about aggregate rates
And what we said and what remains true is that those aggregate rates are consistent with the background
And we've said that the background, there's variability in that background, but those estimates are around 0.8. And so that hasn't changed
It also hasn't changed that we haven't seen anything that we consider a signal
And the aggregate of our monitoring program tells us that all the statements that we've made are still holding
Okay, and so this is Mike
I'll take the question about Stemcentrx and our overall portfolio
So as we mentioned on the call, we have a very robust portfolio overall in R&D
And certainly within oncology, we are building considerable momentum
As I mentioned, we have 20 programs in the clinic, 17 of those are in early development
And that's a mix between Stemcentrx and other AbbVie programs
And so that makes it difficult to give you a percentage that Stemcentrx will represent going forward because, of course, that's going to be based on the total number of programs that advance into later-stage development
What I would say is we're seeing encouraging signs across that portfolio, on stem programs and other programs of activity, so we'd expect to advance a number of those programs
And with respect to your question about targeting technologies, we certainly have a number of ADCs in our portfolio
We feel that the talents we have as an organization fit that very well in terms of our skills in small molecule chemistry and protein engineering and antibody engineering, but we are in no way limited to ADCs
We have very robust capabilities in small molecules, in novel biologics beyond monoclonal antibodies
We have a presence now in oncolytic viruses and other novel means to modulate targets
And so we're going to look at the targets that we have available, and we're going to pick the best modality that we can to address them, and that is in no way going to be limited to ADCs
So small-cell lung cancer remains an area of very, very substantial unmet medical need
The standard of care hasn't changed in many years
And we view it in a positive way overall that there are now some therapies that look like they can make a real difference here, Rova-T included
I'm not sure that the bar has changed substantially though
So for example, if you look at third-line or greater small-cell lung cancer, there are no approved therapies
Response rates based on expert opinion, because there really are no good clinical studies here, would probably be in the low single-digit range, if not zero
And survival is dismal
And as Rick mentioned, with recent I-O releases, objective response rates of 10% or 20% are meaningfully different from that
And so there's a huge unmet medical need here, and there's an unmet medical need that relates not only to response rates but also to getting patients on a course that allows them to have good long-term outcomes
And those longer-term outcomes have been a strength of Rova-T based on its stem cell-targeting approach, cancer stem cell-targeting approach
So while there are encouraging signs, there's still a huge unmet medical need, and I don't think the bar has changed substantially
Okay, so this is Mike
With respect to the RA studies for upadacitinib and what will support an NDA next year, as you mentioned, we have six studies, and those cover a range of patients from methotrexate inadequate responders to biologic inadequate responders
They include active comparator studies and studies aimed to look at structural endpoints
And so we will file with at least five studies of the six
We've always considered five studies our core
There was a sixth study, which is a structural study, which was originally anticipated to take longer than the others, but it is moving forward ahead of schedule
So it's possible that that could actually come in at a time that it can be included, but we're going to continue to evaluate that, but it would either be five or six studies that we would include
Certainly
So with respect to rates across the program, I think the best answer that I can give you is the answer that I gave you in my prepared remarks, which is that we monitor the program in aggregate across all of the studies
And of course, we're still blinded on the majority of the studies and therefore the majority of our database
And when we look at that and when we look at those rates, those rates are consistent with the background rate that we've stated on a number of occasions
We're going to continue to monitor carefully, but we do not see that situation change
I'll also refer to the remarks I made about our DMC
We are firewalled from our DMC by design, but our DMC has access to all of the data, including the unblinded data, and they have consistently recommended that we continue the program without any modifications
And if they had concerns, you certainly wouldn't expect that to have been their course of action
With respect to platelet changes, we've looked at it
We've not seen any changes with platelets
Platelets remain stable on therapy
And I think platelets don't seem to be playing any part of the picture for upadacitinib
In terms of launches in UC and Crohn's, it's early on in those programs
So we're always going to try to move as quickly as we can and advance programs rapidly, but we're not seeing any bottlenecks in sites
We're not seeing any bottlenecks in patients
In fact, recruitment across the program has gone very well, I think indicative of strong investigator and patient interest in the upadacitinib program broadly
