Lars Rebien Sørensen - Chief Executive Officer Kåre Schultz - President and Chief Operating Officer Mads Krogsgaard Thomsen - Chief Science Officer and Executive Vice President Jesper Brandgaard - Executive Vice President and Chief Financial Officer.
Sachin Jain - Bank of America Merrill Lynch Keyur Parekh - Goldman Sachs Michael Novod - Nordea Markets Richard Vosser - JPMorgan Martin Parkhøi - Danske Bank Tim Race - Deutsche Bank Philippe Lanone - Natixis Securities.
Thank you very much and welcome to this Nova Nordisk conference call regarding our performance in the first nine months of 2014 and the outlook for the full year. As said, I’m Lars Rebien Sørensen, the CEO of Novo Nordisk.
And with me I have President and Chief Operating Officer, Kåre Schultz; Chief Financial Officer, Jesper Brandgaard; and Mads Krogsgaard, our Chief Science Officer. Present are also our Investor Relations officers. Today’s earnings release and the slides for this call are available on our webpage, novonordisk.com.
The conference call is scheduled to last approximately one hour. And as usual, we’ll start with the presentation as outlined on Slide #2. The Q&A session will begin in about 25 minutes. Note that the conference call is being webcast live and a replay will be made available on our website. Turn to Slide #3.
As always, I need to provide you that this call will contain forward-looking statements. The forward-looking statements are subject to risks and uncertainties that could cause the actual results to differ materially from expectations. For further information on the risk factors, see the earnings release and the slide prepared for this presentation.
Turn to Slide #4. Sales growth during the first nine months of 2014 was 8% in local currencies and 4% in Danish kroner as compared to 2013.
This growth reflects the expected challenges related to the partial loss of reimbursement and a large pharmacy benefit manager in the United States effective January 01, 2014, generic competition to Prandin, expanded Medicare Part D utilization and adjustments to provisions for rebates in 2013, with the effect of generic Parandin starting to annualize.
We’re satisfied with the sales growth in the first three quarters of 2014, increased to 10% in local currencies. The growth was driven by North America, International Operations and Region China. When looking at products, the growth was primarily driven by Levemir and Victoza.
The rollout of Tresiba, the once daily new generation basal insulin continues. Performance in the countries where market access are on par with insulin glargine remains encouraging. On the R&D front, we’re happy that the European Commission approve Xultophy, the combination of Tresiba and Victoza for the treatment of type 2 diabetes in adults.
At the FDA advisory committee meeting in September, Saxenda received a positive 14-1 vote in favor of approval for treatment of obesity. As announced in September 2014, we decided to discontinue all our research and development activities within inflammatory disorders. Turning to financials.
Operating profit grew 11% in local currencies in the first nine months. In Danish kroner operating profit grew 5% reflecting the negative impact from key invoicing currencies. Diluted earnings per share increased 7%. The outlook for '14 sales growth is now at 7% to 9% in local currencies against previously 7% to 10%.
For operating profit we still expect growth to be around 10% in local currencies. The preliminary outlook for 2015 indicates high single-digit growth in sales and around 10% growth in operating profit, both measured in local currencies. With this, to much more detail and Kåre Schultz on sales..
Thank you, Lars. Please turn to Slide 5. In the first nine months of 2014 North America accounts for 65% of growth followed by international operations and China accounted for 23% and 16% of growth respectively. Sales growth in North America was 11% in local currencies reflecting a continued positive contribution from pricing in the U.S.
and market share gains for both Levemir and Victoza. Sales growth in North America remains negatively impacted by the partial loss of reimbursement at a large pharmacy benefit manager, generic competition for Prandin, expanded Medicare Part D utilization and adjustments to the provisions for rebates in 2013.
However, it should be noted that in the third quarter of 2014 we saw a more modest impact from generic Prandin competition as generic products were first launched in August 2013. Sales within international operations grew by 13% in local currencies, reflecting robust penetration of all three modern insulins.
The growth was partly offset by declining human insulin sales due to lower tender sales as well as the continued conversion of the market to modern insulin. Sales in Region China increased by 14% in local currencies. The sales growth was driven by all three modern insulins, while sales of human insulins only grew modestly.
Sales growth in the third quarter of 2014 was partly offset by stock adjustments and a more modest market growth following the introduction of, among others, the nine ban restrictions. The nine ban restrictions was issued by the Chinese authorities and outlines comprehensive anticorruption compliance requirements. Please turn to Slide 6.
From a product perspective, sales growth was realized within both diabetes care and biopharmaceuticals with the majority of growth coming from modern insulin and Victoza. Within modern insulin, growth is primarily driven by Levemir, which accounts for 51% of the growth measured in local currencies.
Sales of NovoSeven decreased by 2% in local currencies and by 6% in Danish kroner. The sales development reflects declined sales in Europe and North America partly due to cost containment which only are partly offset by growth in international regions.
The market for NovoSeven remains volatile as it depends on the number of surgical procedures undertaken on hemophilia patients with inhibitors. Sales on Norditropin increased by 10% in local currencies and by 5% in Danish kroner.
The sales growth is primarily derived from North America and is driven by contractual wins that support programs that Novo Nordisk offers healthcare professionals and patients as well as the demand for the prefilled FlexPro device. Please turn to Slide 7. Victoza sales increased by 15% in local currencies during the first nine months of 2014.
Sales growth was primarily driven by North America accounting for more than 80% of growth. Despite the lower volume growth both in the U.S. and Europe, the GLP-1 segment value share of the total diabetes care market has increased to 6.9% from 6.7% in 2013. Victoza retains clear leadership within the GLP-1 segment with a value market share of 72%.
In North America, sales of Victoza increased by 20% in local currencies. This reflects a positive impact from pricing and the continued growth of the GLP-1 class. The growth is however somewhat reduced by the partial loss of reimbursement with a large pharmacy benefit manager in the U.S.
The GLP-1 class value share of the total diabetes care market is 8.4% which is comparable to the level last year. Victoza remains the clear market leader with a 69% value market share compared to 66% a year ago. During the first nine months of 2014, Levemir grew by 29% in local currencies, accounting for 51% of total growth.
Growth of Levemir was primarily driven by North America where sales increased by 46% in local currencies. In Japan and Korea the growth for Levemir was negatively impacted by the strong uptake of Tresiba in Japanese market. In the U.S., Levemir continues its solid trajectory.
During the last year Levemir has gained more than two market share points in the modern basal insulin segment. This performance is driven by a strong commercial and promotional progress in our U.S. organization. Since August, this is further supported by direct-to-consumer campaign called Today.
The recent launch of the new FlexTouch device is further differentiating Levemir. FlexTouch is the first and only prefilled insulin pen with no push button extension. The previously available device called FlexPen was discontinued in the beginning of October. Please turn to the next slide for an update on the Tresiba rollout.
The rollout of Tresiba continues to progress with encouraging feedback from both patients and prescribers. Tresiba is now commercially launched in 22 countries, recently in Brazil, Slovakia, Chile and Russia.
The countries where Tresiba is reimbursed on a similar level as insulin glargine it continues to steady grow its share of the basal insulin market. In Japan 20 months after launch, Tresiba has reached 24% of the basal insulin market measured as monthly value market share. In September 2014, Ryzodeg was launched in Mexico.
The launch activities are progressing as planned and early feedback from the patients and prescribers is encouraging. Please turn to the next slide. Zooming in on Japan, we can see that since the launch of Tresiba in March in 2013, Novo Nordisk basal insulin market share has increased by more than 10 percentage points to 39% in August 2014.
The strong launch of Tresiba reversed the decline in Novo Nordisk’s total insulin market share. Novo Nordisk has increased its leadership to 55% in August 2014 from 54% prior to the launch of Tresiba. Now over to Mads for an update on research and development..
Thank you, Kåre. Please turn to Slide 11. I’ll start with an update on DEVOTE. Recruitment is progressing ahead of plans and the majority of the 7,500 participants have now been recruited. We now expect data to support a pre-specified interim analysis of MACE to be available early 2015.
Completion of the trial is still expected to be within three to four years from trial initiation in October 2013. As you know, there has been much debate on the topic of how to best use interim analysis as the basis for potential FDA action while preserving the integrity of the ongoing cardiovascular trial.
Reflecting this, we previously indicated that one approach to postpone the risk of introducing bias in the DEVOTE trial for as long as possible would be to submit the interim analysis to the FDA regardless of the hazard ratio observed at the point of the interim.
On August 11th, FDA hosted an advisory committee hearing on interim analysis of cardiovascular outcome trials and we subsequently also received specific guidance from the agency on the best path forward for DEVOTE.
On this basis, we now expect to decide during the first half of 2015 whether to submit based on interim data or to await the completion of the DEVOTE trial. The decision will take into consideration both specific FDA guidance to the company and the general FDA guidance from the CV guideline published in 2008.
I’d like to stress that our confidence in both the cardiovascular safety of Tresiba and the ability of DEVOTE to document this remains unchanged. The challenge is simply that interim analysis inherently carry a higher level of uncertainty because we have faced on a much lower number of observations than the final results.
This means that there is a risk that the interim analysis may not support a resubmission in some studies where the final results do. Consequently, if we at the time of interim analysis should decide not to resubmit the NDA with interim data to the FDA, this would not indicate that there is a cardiovascular safety issue related to use of Tresiba.
Regarding safety, if a signal were to emerge at any point, the independent data monitoring committee overseeing the DEVOTE trial could, as in any such trial, recommend trial termination.
Before I end my update on DEVOTE, let me tell you on how we intend to restrict the access to the interim data within Novo Nordisk to preserve the integrity of the ongoing blinded trial until its completion. At present, the DEVOTE study remains blinded both to Novo Nordisk and to the regulatory authorities.
Access to the interim data will be restricted to small unblinded team within the Company. The same team will interact with the FDA and decide whether to resubmit the degludec file including the interim data. Management will not have access to the unblinded results of the DEVOTE interim analysis and the results will not be communicated externally.
Please turn to the next slide. In September 2014, we announced that Xultophy had been approved by the European Commission.
Xultophy has indicated for the treatment of adults with type 2 diabetes to improve glycaemic control in combination with all glucose-lowering products when these alone, or in combination with basal insulin do not provide adequate glycaemic control. Xultophy is a fix combination of insulin degludec and liraglutide.
The product is characterized by the complementary mechanisms of action of the two long acting GLP-1 and insulin molecules to improve glycaemic control in a safe manner. The European label reflects the strong results from the clinical development program.
Thus, Xultophy has demonstrated a significantly reduction of HbA1C of 1.9% with a mean weight loss of 2.7 kilograms in the DUAL II study. We expect to launch Xultophy in the first European countries in the first half of 2015. Please turn to slide 13 for an overview of some other key development milestones.
In October 2014, we initiated a 30-week Phase 3a trial for our once-weekly GLP-1 analogue, semaglutide. The trial compares semaglutide with sitagliptin in around 300 Japanese people with type 2 diabetes.
Furthermore, we’ve successfully completed Phase 1 development programs for the two oral GLP-1 tablet formulations, OG987GT and OG987SC, products combining the long acting 987 GLP-1 analogue with either of the carriers GIPET or SNAC.
The Phase 1 trials comprised 305 and 145 healthy volunteers respectively and both product candidates were associated with statistically significantly greater weight loss than placebo. We’ve also now started the first Phase 1 trial for LAI338, a new long-acting insulin analogue.
The trial is expected to include approximately 70 healthy volunteers and people with type 1 diabetes. Within obesity, we have following the positive 14-1 vote at the FDA outcome meeting for Saxenda at September 11, continued the constructive dialogue with the FDA hoping to complete the regulatory process as soon as possible.
In September, we initiated the first Phase 1 trial with G530L, a novel glucagon analogue targeted to be used in combination with liraglutide as treatment for obesity. The trial will investigate single doses of G530L alone and in combination with liraglutide in approximately 160 overweight and obese, but otherwise healthy male subjects.
In September 2014, we announced the discontinuation of all R&D activities within inflammatory disorders. The decision followed the review of Novo Nordisk's strategic decision in the therapeutic area after the discontinuation of the most advanced compound anti-IL-20 for the treatment of rheumatoid arthritis.
With that, over to you Jesper for the financials..
Thank you, Lars. Please turn to Slide 14. In the first nine months of 2014, sales increased by 8% in local currencies and by 4% mentioned in Danish kroner to 64 billion. Reported gross margin improved by 100 basis points to 83.6 in the first nine months of 2014.
The reduction of the cost of goods sold reflects an underlying improvement on favorable price development in North America, a positive impact on product mix primarily due to increased sales of modern insulin and finally from improved productivity.
This is partly offset by around 0.2 percentage point due to the depreciation of key invoicing currencies versus the Danish kroner. Sales and execution cost increased by 1% in local currencies and decreased by 2% in Danish kroner to 16.5 billion.
The modest increased in cost reflects investments in sales force expansions in the U.S., China and selected countries in international operations. Also, the provision for contribution to the Branded Prescription Drug Fee in the U.S. introduced with the 2010 Affordable Care Act in the U.S.
increased reflecting the revised and final regulations issued in the third quarter of 2014. These sales and distribution cost drivers was largely offset by lower promotional spend in the U.S. and Europe. Research and development costs increased by 23% in local currencies and by 21% in Danish kroner to 9.9 billion.
The significant increase in cost reflects the progression of the late stage diabetes care portfolio. Additionally, as mentioned by Mads, DKK 600 million one-off cost incurred in the third quarter of 2014 relating to cost for the discontinuation of all activities within inflammatory disorders.
Operating profit in local currencies increased by 11% and by 5% measured in Danish kroner to DKK 25.3 billion. Net financial showed net income of DKK 409 million compared to an income of DKK 610 million in 2013. The foreign exchange result was an income of DKK 414 million compared to an income of DKK 696 million in 2013.
The result reflects gains on foreign exchange hedging involving efficiently the Japanese Yen due to its appreciation versus the Danish kroner compared to the prevailing exchange rate in 2013. The effective tax rate for the first nine months of 2014 was 22.5%.
The decrease of 0.2 percentage points versus last year reflects an effect from the gradual lowering of the Danish corporate income tax which will occur from 2014 to 2016. Please turn to Slide 15.
The negative impact from currencies and operating profit we have experienced during the first nine months of 2014 has primarily being driven by the depreciation of the Japanese Yen and the U.S. dollar. However, during the last three months, our key invoicing currencies have appreciated against the Danish kroner in particular the U.S.
dollar which since August have depreciated by 5.5%. This development has reduced the expected full year impact from currencies on our reported numbers for 2014.
Furthermore, at the spot rates as of 27th of October, we expect this appreciation of our key invoicing currencies will be reflected in the positive impact on reported sales and operating profit in 2015. The positive impact would be partly offset by losses on hedging contract reported as part of net financials.
For For your reference we have on this slide updated the annual impact of operating profit from a 5% movement in the average exchange rates. We have also outlined the financial hedging in month for the key currencies. Please turn to slide 16 for the financial outlook. Sales growth for 2014 is now expected to be 7% to 9% measured in local currencies.
Updated outlook for 2014 primarily reflects lower expectations towards NovoSeven sales globally and a lower market growth in China. Given the current level of exchange rate versus the Danish kroner, the reported sales growth is now expected to be around 2 percentage points, lower than the growth measured in local currency.
In 2014 operating profit growth is still expected to be around 10% in local currencies. Given the current level of exchange rate versus the Danish kroner, the reported operating profit growth is now expected to be around 3 percentage points lower than the growth measured in local currencies.
Operating profit is maintained despite the revised outlook for sales growth and the cost associated with the discontinuation of activities within inflammatory disorders. This reflects lower expectations to cost related to back office function as well as reduced promotional investments.
For 2014, we expect a net financial loss of around DKK 150 million. This primarily reflects losses associated with foreign exchange hedging contracts following the recent appreciation of the U.S. dollar versus the Danish kroner compared to the average prevailing exchange rate in 2013.
The effective tax rate for 2014 is now expected to be around 22% to 23% from previously 22%, reflecting a negative non-recurring impact from the increase in the non-tax adoptable provision related to the branded prescription drug fee in the U.S. as mentioned before.
Capital expenditure is still expected to be around DKK 4 billion primarily related to investments in additional GLP-1 manufacturing capacity, expansion of filling capacity, prefilled device production facilities, as well as expansion of protein capacity for clinical trial supplies.
Depreciation, amortization and impairment losses are now expected to be around DKK 3.5 billion. This increased chart is reflecting the discontinuation of all activities within inflammatory disorders. The free cash flow for 2014 is still expected to be around DKK 25 billion.
With regard to the financial outlook for 2015, we expect to provide detailed guidance in connection with the release of the full year result for 2014 in January. At present preliminary plans indicate a high single digit growth i.e. in the range of 6% to 9% for sales and around 10% growth for operating profit both measured in local currencies.
Adjusting 2014 for the impact of the discontinuation of all activities within inflammatory disorders, the underlying operating profit growth in 2015 is expected to be similar through the expected growth in sales both measured in local currencies.
The preliminary plans for 2015 reflects expectation for continued robust performance of the portfolio of modern insulins Tresiba and Victoza as well as modest sales contribution from Xultophy. The sales drivers are expected to be partly countered by increased rebate levels in the U.S.
and intensifying composition within both diabetes and biopharmaceuticals. All of the above expectations are based on the assumption that the global economic environment will not significantly change business conditions for Novo Nordisk during 2014 and 2015 and the currency exchange rate especially for the U.S.
dollar will remain at the current level versus the Danish kroner. With that, over to Lars for closing remarks..
Thank you to my colleagues. Turn to Slide #17. To summarize, we are pleased to reiterate our expectations to operating profit growth for 2014 despite a challenging year and the revised outlook for sales growth.
We remain encouraged by the performance of Tresiba in key markets and look forward to the launch of Xultophy in Europe in the first half of 2015. We’re now ready to take the first Q&A where I as always kindly ask you all participants to retain themselves to two questions. Operator, we’re now ready to take the first question..
Thank you (Operator Instructions) We will now take our first question from Sachin Jain, Bank of America. Go ahead, your line is open..
A couple of questions. Firstly, could you provide some color on what net U.S. insulin pricing is reflected in guidance for full year 2015? Clearly, the question is in light of Sanofi's commentary earlier in the week that they believe a price war is beginning there. And related, any color you can give on the net price, i.e.
post rebate, price differential between Levemir and Lantis in the U.S.? Clearly, there was some differential at launch. Does that still exist? Has it narrowed at all? And then the second question is for Mads, on the DEVOTE interim analysis. You say you've received some specific guidance from the FDA.
Could you provide any color on that? And I guess specifically, do you have any view now or agreement around what the point estimate and upper end confidence interval for that interim should be?.
And let’s start with the core and yes, you can decide whom you want to answer this, what net U.S. pricing has been included in the guidance that we have given for 2015 and whether or not there are any difference between the net price levels of Levemir and Lantis..
So, if I just start with a comment on what the assumption have been included for the 2015 and then Kåre if you can give more detailed comments on the pricing situation between Levemir and Lantis in the U.S. The assumption for the U.S pricing in the outlook we’ve given now is a modest positive to flat prices in the U.S.
in terms of impact on gross margin and we’ve also loaded in the nine-month results that we’ve had a positive pricing impact in 2014 and hence in 2015 a slight positive to neutral impact from prices on our gross margin in '15 and also leaving us with the total impact in development on gross margin in 2015 in the 50 basis point range basically coming from improved product mix and also to some degree productivity maybe with the slightly positive pricing impact.
Kåre?.
Yes, and I would just like to highlight the fact that this is a complex topics with many moving parts because from our point of view you can say at the end of the day it is the net ARP per unit of insulin that really drives the business and that is of course a combination of the product mix, it's effect of list pricing, it’s effect of the various different rebates that are being paid in the U.S.
And as I am sure you all know, some of these rebates are related to the government, so like the Medicaid, some of the Medicaid Part D are sort of in between, there is also the Managed Care. And with the Affordable Care Act there has been changes in the channel mix and changes in some of these rebates.
And then of course there is the whole negotiation with PBMs where individuals customers have individual contracts and that can also affect the net pricing.
So the result of all these moving parts is, as Jesper alluded to, and I think it’s getting to very detail discussion about the specifics of each and every one of them would be very complex and would not necessarily lead to a better overview than the one that Jesper provided.
With regard to your specific question on Levemir and Lantis, I can’t really comment on it. I can only say that with regard to Levemir we have over the last years increases in list price. We have also seen increases in net ARP, but we are also seeing increases in absolute rebates..
Thank you very much Kåre for that. And then we turn to Mads Krogsgaard. You mentioned in your manuals specific guidance from the FDA regarding the DEVOTE interim analysis and then there is questions, so what is that specific guidance.
And even more specifically, whether that specific guidance included anything about what constitutes a reassuring point estimate?.
First of all, we all or many of us heard the August 11 AdComm about the general use of interim analysis in cardiovascular outcome trials. And to that end I think we have received more deliberations and had more discussion with the agency as that specifically relates to the DEVOTE trial.
And quite frankly, I think, when you do things the way that we have now decided and designed the study to be done also in terms of having data that firewall between the very small unblinded team, the rest of the company et cetera, the external statisticians.
I think we can safely say that we have done the ultimate of what can be done to preserve the integrity of the entire trial regardless of the conduct of the interim analysis and safe to say is that the agency actually has just put agreement with this.
So that means that we have a path forward of exactly how to handle this, also exactly which data are to be submitted. As you know, it's only a -- not only a small data set compared to the full trial, it's also only a small subset of the full trial data. Obviously, the FDA would decide to see at this point.
Then comes the question about the numbers and I think, I mean a number is never just a number, the number should be seen in the context of its surrounding and that means that in as much as the confidence into upper 95% found of 1.8 as per the December 2008 guideline is kind of the carved in stone.
The point estimate that will be considered reassuring should be seen in the light of the surrounding data set, they will also be receiving serious adverse events other things they might have asked for. And enhance I can’t really responds at this point in time. So, we’re simply looking very much for what will happen in the first-half of next year..
We will now take our next question from Keyur Parekh, Goldman Sachs. Please go ahead. Your line is open..
Good afternoon. Thank you. And I'll spare the remaining question for everybody else on the call. Two questions, please. First, Jesper, can you just help us think though the S&D number in the quarter? I believe that included some kind of true-up on the U.S. excise tax.
If you can just help us think about the impact of that, both on that line and the tax line, and how we should think about those numbers for 2015.
And then secondly, Mads, can you just help us think about what you are seeing in the sense of the CV event rate for the patients you have on Tresiba in Europe and in Japan? And from a communication perspective, should we expect Novo to announce that they have decided to file Tresiba or not, or will that communication to the investor base happen only after the FDA's decision on whether to accept the filing or not?.
Yes of course, S&D numbers and what is included around the specific U.S. numbers and whether that has implication for 2015..
We did have the challenge that we had new regulation hitting us in relation to the manufacturers fee and their attitude that we have in the third quarter of this year expensed what would be a normal for five quarters and fit for one quarter.
So, if you basically state what the extra one-year charge is for this fee it basically is equivalent to slightly more than DKK 400 million which is kind of a non-recurrent cost that's been taken in through the S&D line and that’s the key non-recurring item in that line. Apart from that, the rest of the things are ongoing cost base.
The unfortunate thing about this manufacturers fee is however that is for U.S. tax purposes, it's a non-tax deductible expense and hence the non-recurring or the non-deductibility leads our tax rate everything else being equal to go up by 30 basis points and that is reflected in the updated expected full year tax rate.
And the tax rate that has been used after nine-month is the tax rate that we expect to be prevailing for the full year around 22.5%. But that of course leads to a higher specific tax rate in the third quarter alone. But that is just adjusting the full year tax rebate of this manufacturing fee. I hope that was clear..
The next question is about, if I recall correctly, the CV event rate from the already marketed product in Japan, Tresiba in Japan and Europe or rather perhaps maybe a more general comment on what’s your expectations for event rate in the DEVOTE study should be compared to? And then finally a communication question whether we’re going to disclose and whether we file or not?.
The lines of evidence as to cardiovascular safety that go beyond just what we saw in the BEGIN program are at least threefold. One is as you allude to the Japanese and European performance, i.e. the pharmacovigilance systems, what is in the [indiscernible] system, what is in our system. And so that thing I can say is actually not much.
As you know it's very difficult to pick up anything unless we have very dramatic signals from such databases, but indeed there is no such signal at all. We’ve also done the first Periodic Safety Update Report, the PSUR, with Europe without giving rise to any new cause for concern.
As regards the overall program, we have to take more than 22 studies involved in the Phase 3b and 4 program and when we put all those together also I can say that there is no either new or changed cause for concern as per those studies at all.
In Japan we've also committed to do, as we always do for new molecules, a kind of a safety monitoring study in a few thousand patients for a couple of years after approval and that is still ongoing so I have no findings from that one. As regards the communication....
Before we go to the communication, expectations for the event rate in the DEVOTE study. That's critical to when we will be able to finalize....
So again, I think there is no doubt that the original planning of the study that included a 2 plus percent annual MACE event rate and here we’re talking MI, stroke and death. That as you know is obsolete and what we’re witnessing is what I would call a more legalized situation. And as you recall LEADER is 3 plus in MACE annual event rate.
I cannot be more specific than that because it’s still early days, but this is of course underlying the basis for the upgraded guidance as to the duration of the study that you recall we’ve given you over the last six months or so.
These patients in general has based on demographics that are slightly more sick than those in the LEADER trial, so best estimate I can give you is a LEADER or something maybe slightly exceeding LEADER, that’s kind of what we’d expect. We have no data or the data we have is at this point still uncertain.
Well I should then relate to the guidance on communication, well basically I think what is most prudent as we’ve discussed in management is that on the date where we hear from the unblinded team that has discussed with the FDA at a pre-NDA meeting the situation, then once we are informed by them not about any data or any other outcomes, but by whether they will submit or not, this is the communication that will be given to the market and it will likely be supplemented with information even when the FDA has acknowledged the receipt of the dossier and that they will review it with a six month time span, we would expect to communicate that as well..
So no results, but filing or no filing in the first half of next year. Thank you very much for those questions and we’ll move on to next question, please..
We will now take our next question from Michael Novod, Nordea. Please go ahead, your line is open..
It's Michael Novod from Nordea in Copenhagen. One more question to DEVOTE, just to understand.
We all know the FDA's caution regarding integrity and interim, but can you also say something about has this been driven solely by that or also by an increase in concern for the FDA with regard to interim analyses as such and results of interim analyses, also with regard to Tresiba, i.e.
is there a more likelihood of this being submitted on an interim analysis? Secondly, to NovoSeven and the disappointing Q3 number, just maybe you could help a bit about doing modeling on this going forward. We know there's volatility in sales.
What do you expect for Q4 and how should we see that going into '15 and '16?.
Lars Rebien here.
And Mads Krogsgaard, can you talk a little bit further to the question about whether or not there was general concerns about interims or it was concerns about the integrity of the trial which led our discussion with the agency and how we’re communicating now?.
Yes Michael, first of all, I think we can put to rest the notion that some people have been bogged down with namely that interims were dangerous to do and you would not be able to – it will be very muddy waters, you would taint the rest of the study and so on.
I think both the August '11 AdComm revealed that if you do your work diligently and properly with the right firewalls with the right blindings of the studies, which is the case for DEVOTE, and you negotiate all of that with the regulator, you will actually be in a good shape regarding preservation of the integrity of the residual of the trial and this is totally reflected in the communication between the agency and Nova Nordisk.
And actually the agency is also suggesting that companies like we should actually contribute to informing the market that indeed one can do interims without this first of all indicating or invalidating the residual of the trial.
And we should also like to state that when you do an interim, it doesn’t mean that the interim necessarily will be robust enough as to actually reassure the agency about either the confidence interval which is an easy thing to do because that’s very binary or for that matter what constitutes a reassuring point estimate.
And that means that to your specific question, is there now a smaller likelihood of approval, yes or no.
what I would say has happened here is that aggregate risk in essence has now been split into two, because if you recall the theoretical scenario that Novo Nordisk put forward one quarter ago where we basically said that we intended to submit the interim analysis as part of a class two resubmission of the NDA to the agency in the first half of next year that incurred by definition risk that the point estimate would not be reassuring even seen with the eyes of Novo Nordisk.
But we would have at that point decided to do so to kind of get it to the agency and then postpone the risk of what could be a biasing of the residual trial until the very end of the FDA action period. Now the FDA didn’t quite agree with that notion.
They’re basically saying let’s have discussions, let’s look at your data and if we feel you should submit these data, that is when you submit and that’s why the unblinded team is meeting with the FDA. And that basically also means that now you had the risk that we’ll not submit based on the interim.
But when we submit, it has been discussed with the agency and the agency at that point has actually been in concordance with the notion that is resubmitted So the overall risk, short answer, is the same..
Thank you, Mads. Then over to Kåre. Very disappointing NovoSeven numbers in Q3 and obviously it is quite volatile as you mentioned in your presentation. So, what are your expectations for the remaining of the year and into '15 or even '16 if you're at all speculating that far out..
That’s correct. When we look at the first nine months, then we see a very negative third quarter and overall we see sales 2% down basically driven by Europe and significantly down small negative in North America and the other regions actually having some healthy growth in NovoSeven.
It is very difficult to predict with NovoSeven because it varies a lot based on extraordinary bps and based on operations under the cover of NovoSeven.
I would say that overall we should estimate to see flat sales development for this year and the coming years and then there will be few swing factors such as the extent to which we see biosimilars in some of the emerging market and the extent to which we see economic recession in Europe basically having effect on demand for NovoSeven in Southern Europe.
So it is hard to predict and my best estimate right now is that we should expect flat sales this year and the coming years..
Thank you very much, Kåre. Yes, this is a further disappointment against previously where we have said low single digit. But it’s in the ballpark of where we have guided previously. Next question, please..
We will now take our next question from Richard Vosser, JPMorgan. Please go ahead, your line is open..
Sanofi recently highlighted that they think they had sales force deficiencies in the U.S. So, just wondering, going into 2015 with potentially your competitor putting those rights. Whether you think you might need to increase the spend behind the basal insulin sales force in the U.S.
to head off further competition there? And then second question on Victoza, I think we're seeing the beginnings of some share loss to Bydureon's new, I suppose, shake n' vac pen, or the new pen, at least.
Just wondering, is there anything you can do there to head that off? And what do you expect on Victoza going forward? Clearly, of course, with dulaglutide coming, this suggests that Victoza is going to be under some pressure, so what are you expecting in '15 in the guidance?.
And I guess this is for your Kåre. Sales force deficiency was mentioned as part of the explanation for Sanofi’s performance and expectations for the next year.
Does that give you any course for readjusting our course of action, and are you worried about them getting their act together so to speak if I may say so?.
And I think it’s probably most right now to comment on the performance of their sales force. But I can comment on the performance of our own sales force and I am very happy with the performance of our sales force in the space of basal insulin.
We’re very happy with the market share gains we’ve been seeing consistently on Levemir over the last couple of years. This continues as we speak. We have operated the device from the FlexPen’s to the FlexTouch.
As I mentioned before, FlexTouch is a unique prefilled device which is based on a spring mechanism with high quality Swiss springs, ensures a self injection once you touch the push button. This is new in the space of prefilled devices. It is more convenient and it is further strengthening we think the attractiveness of Levemir in the U.S. marketplace.
So, the short version is I don’t have any plans to sort of dramatically change the size and the way our sales force works. We’re very happy with the way it’s working right now..
Thank you, Kåre. And then to another question on Victoza and according to Richard, the alleged market share loss to Bydureon’s new device, I don’t recall that to be the case. But you may comment on that.
And perhaps even more so what are your expectations when we get to release the dulaglutide onto the market?.
You can say that in the GLP-1 space Victoza is the gold standard [indiscernible] as you saw a worldwide [9-10%] market share I don’t there is going to be any change in the perception about the relative strength in the products for Victoza into this basic [indiscernible] clinical profile and it has been proven over and over again that Victoza has a superior clinical profile.
However, every time there is a launch of new product, you will see NBRx data react quite violently due to the nature of new launches and sampling. And this was seen before and we have all the time seen a steady development of the GRx share so to speak.
With the launch of the new pen, new Bydureon pen I don’t think we should expect any major changes in market dynamics with the launch of Trulicity hopefully we will see an increase in the total volume of GLP-1 use in the U.S.
GLP-1 is a very attractive therapy for Type 2 diabetes and if our competitor is able to bring more patients onto the GLP-1 segment that would only be good for patients. So we expect the Trulicity will more expand the market than directly take market away from Victoza..
And this at least seems to be confirmed by the statements made by Lilly recently. So that would be our expectation. Next question, please..
We will now take our next question from Martin Parkhøi, Danske Bank. Please go ahead, your line is open..
Martin Parkhoi, Danske Bank. Firstly, again back to the DEVOTE study and a potential resubmission. Just to be absolutely sure that you say that in the first half next year you will take the decision to resubmit.
When you take the decision, are you then ready to push the button right away, so you actually also make the submission in the first half, as you stated, in connection with the second quarter result? And in that respect, Lars also at that time stated that a launch could take place in early '16.
Is that still your base case scenario? And then a question to Jesper on the inflammation. Of course, you closed down your inflammation activities this year.
Have you included that you will reinvest all the savings from that closure in your 2015 guidance, or is there included that you will not be able to reinvest the savings from that close down?.
Thank you very much Martin. This is Lars Rebien here. Regards to the first question, we can confirm the statements that we’ve made. Yes, we will be in a position to make decision to file and we will file in the first half of '15 a resubmission if the data are convincing, so that’s clear. The same method as we said in connection with the half year.
Then inflammation whether or not those savings have been fully reinvested in the and included in the 2015 guidance..
We’ve actually been very specific about in our guidance because we -- you can see in our account that we have 600 million in extraordinary cost in 2014. And 2015 we don’t expect to have the same cost, i.e. they have not been reinvested and that’s the reason why the guidance for operating profit growth is 10% in local currencies.
If you adjust for that single factor, the underlying growth is the same level of growth i.e. high single-digit growth 6% to 9% or so sales and for operating profit and that means everything else being equal, we would assume an unchanged operating margin if you adjust for this information. I hope that’s clear..
Yes, I understand that. I understand with respect to the 600 million is related to the closure, but you also had some annual cost for having the inflammation business doing R&D research.
So what I am asking is that are you expecting a lower R&D budget in '15 as you will not invest in R&D for the inflammation business? So it's not on the one-off cost in '14, more related to if you have made any kind of R&D savings by closing down inflammation..
I think the one-off cost will be a permanent saving as regard to other cost, you should anticipate that the overall R&D ratio adjusted for this will be largely unchanged and that’s reflection of continued investment in the full portfolio of the diabetes care studies, including of course running in 2016 with a fully recruited DEVOTE trial where we expect it to be basically fully up and running from end of the year..
So this is Lars Rebien here. So the general exercise in closing down our inflammation we said was not to save money, but there are some costs associated with it. Going forward largely we will be reinvesting those activities into diabetes.
And then we just add, I didn’t comment on one of your earlier questions regarding launch, potential launch of Tresiba in the U.S. and we can confirm again that it is early '16 which is the intended potential launch timing if we file an interim and if the interim is approved by the agency..
We will now take our next question from Tim Race, Deutsche Bank. Please go ahead. Your line is open..
Just first a quick one, I suppose, on -- well, liraglutide in obesity. What's the current situation? You've obviously had a discussion with the FDA post the PDUFA passing. Could you just give an update there? And then just a question on contracting. There's been a surprising lack of questions on this call about it.
But could you just describe what's really changing in the contracting that you're seeing in terms of how long are contracts? Could you describe what payers are now asking to be built in terms of price protection going forward, and whether you're seeing contracting across single products or multiple products more and more? So, perhaps talk about how it is today versus how it was last year and the year before? I'll leave it there..
Thank you very much. Saxenda, as it is called, yeah it's a difficult one, it's only math, can you comment on the dialogue and the nature of that and sort of give a little bit of…..
Yeah, so not really not so much, Tim. What we can say is that of course since the 14 to 1 AdComm on September 11, we have been in a closing constructive dialogue with the agency. So, basically that’s what we can say and then just hope that we can be able to get back to you sooner rather than later with the FDA action.
That’s all that I can say at this point, unfortunately. But we’ll be back..
And then Kåre, the general nature of contracting, can you shed a little bit of light on whether you see change in the overall design of these contract in terms of duration, in terms of price protection, whether we are seeing more exclusivity or whether we are continuing what we have seen in the past [indiscernible]..
Yeah, you could say it is not a question that is easy to answer briefly, because for each segment in which we operate in, if you take our entire portfolio in the U.S. then the contracting environment is slightly different. There is a big difference whether you talk fast acting insulin basal insulin GLP-1 growth hormone and NovoSeven and so on.
But I assume that the question mostly relates to modern insulins.
And in the modern insulin space you could say we have always been sort of a believer in having a rechoice to the doctor and the patient so we basically support that there is access to more than one product in each category and that’s what we’ve been striving for it’s quite clear that from the PBM side there has been a desire to have more exclusive contracts and in that connection increase rebates.
We try to maneuver in this landscape the best we can and have done so for many many years. And of course we want to have good lasting relationships with both PBM and managed care organizations and we want to remain competitive.
And as a consequence of this you have seen that some contracts in segments where there is very similar products, you could say in segment such as the fast acting insulin segment there they has the tendency to have sometimes longer contracts, higher rebate levels and more price protection whereas in other areas where the products are more uniquely differentiated, there is less so.
But to getting more specifics than that I think would take too far..
Thank you very much. And then ladies and gentlemen, since it is getting close to Christmas, why don’t we take one additional question? So the last question, please..
We will now take our next question from Philippe Lanone, Natixis. Please go ahead, your line is open..
Thank you for this Christmas present. Just a question on obesity. Could you, Mads, give us, elaborate a bit on the new glucagon analogue and what are its advantages and why it's not developed first in diabetes? And also, about semaglutide, you alluded to the idea about a possible development in obesity.
Can you update us on that?.
Thank you very much. Mads, it’s a wonderful question to you..
So the glucagon analogue, as you know glucagon has an extremely short half life in a matters of few minutes. What we’ve managed to come up with here is a physically, chemically, permanently stable analogue with a very prolonged half life.
Now why would you do that? You do that because it has been demonstrated from the experiment of nature called oxyntomodulin where cells in the gut actually produce a precursor stage of GLP-1 that binds both to the glucagon and the GLP-1 receptor albeit with different affinities and this oxyntomodulin has documented greater weight lowering effect than native GLP-1 in its own right.
This can give rise to the speculation that if you tweak the dose of glucagon in the low end I have to say with a therapeutic dose of GLP-1, you’ve been in very good situation and have a synergistic effect giving greater weight loss, maybe double digit weight loss as compared to 8% with Saxenda.
So the reason why we’re not creating oxyntomodulin or by specific antibodies with agnostic effect or whatever is that we as a company believe that the data that we are seeing in animals have really getting rise a lot of confusion as regards to ratio you need. So our approach is making a ratio where we define the ratio after human experiments.
So right now the human is being used in a way as the ultimate experimental animal to define the exact ratio of the fixed ratio combination which we’ll update you on even when the trial pans out successfully..
And Mads then on semaglutide, I know you have some very, very exciting brain scans on semaglutide than Victoza, but quickly do it sort of short..
The short version is that we have data that may explain the enhanced weight loss that semaglutide has demonstrated both in animals and humans and the data basically suggest that at the level of the appetite control center in part of the brain called the arcuate nucleus, we seem to have greater accumulation of semaglutide than Saxenda and this basically then would explain a more sustained and pounced efficacy.
That product management we’ll look into later this year with the aim of potentially starting Phase 2 dose range finding trials next year..
That was a Christmas present for anybody interested in obesity. And with that ladies and gentlemen, we’d like to thank you for your interest in our company here at nine months. We will, as usual, be back whenever something exciting happens with our company or when the full year results are released in January 2015..