Sanofi 1Q16 – Diabetes portfolio down 5% YOY at constant exchange (6% as reported) to €1.7 billion (~$1.9 billion); Lantus (insulin glargine) sales down 11% YOY at constant exchange (12% as reported) to €1.4 billion (~$1.5 billion) – April 29, 2016

Sanofi gave its 1Q16 update this morning in a call led by CEO Mr. Olivier Brandicourt. Sales of the company’s diabetes portfolio fell 5% year-over-year (YOY) at constant exchange (6% as reported) to €1.7 billion (~$1.9 billion) in 1Q16. Sequentially, sales fell 9%. The continued downward trend of Sanofi’s diabetes portfolio is largely attributable to the continued fall of flagship Lantus (insulin glargine) revenue, though Apidra (insulin glulisine), Insuman (human insulin), and Amaryl (glimepiride) experienced declines as well. In prepared remarks, Sanofi management barely discussed the performance of the diabetes portfolio, focusing much more on its PCSK9 inhibitor Praluent (alirocumab) and other disease areas. In one of its few comments on the topic, Sanofi emphasized that “the main message here is that our global diabetes franchise continues to perform in line with the revised guidance from last October,” which predicted a decline in diabetes sales of 4%-8% each year through 2018.

On the pipeline front, Sanofi shared that FDA decisions for Lyxumia (lixisenatide) and LixiLan (lixisenatide/insulin glargine) are expected in July and August 2016, respectively. Management also briefly noted that phase 3 SORELLA data for Sanofi’s insulin lispro biosimilar is expected in 2Q16 and phase 3 trials for Hanmi-partnered GLP-1 agonist efpeglenatide and Lexicon-partnered SGLT-1/2 dual inhibitor sotagliflozin are expected to initiate in 4Q16. Our top four highlights from the call are below, followed by detailed discussion and commentary on the financial results for each product in Sanofi’s diabetes-related portfolio, discussion on Sanofi’s pipeline, and relevant Q&A.

1. Lantus (insulin glargine) sales fell 11% YOY in constant currencies (12% as reported) to €1.4 billion (~$1.5 billion).

2. Toujeo sales reached €103 million (~$114 million) in 1Q16, a nearly 15-fold increase compared to 1Q15, the product’s first quarter on the market.

3. GLP-1 agonist Lyxumia (lixisenatide) grew 13% at constant exchange and as reported to €9 million (~$10 million). Sanofi expects US regulatory decisions for lixisenatide and LixiLan (lixisenatide/insulin glargine) in July and August 2016, respectively.

4. Sales of Sanofi/Regeneron’s PCSK9 inhibitor Praluent (alirocumab) totaled €12 million (~$13 million) in 1Q16, a nearly 2.5-fold increase from 4Q15 sales of €5 million (~$6 million).

Table 1: Summary of 1Q16 financial results for Sanofi’s diabetes drug portfolio

Financial Highlights

Overall Diabetes Portfolio

• Sanofi’s overall diabetes portfolio continued to face a challenging quarter in 1Q16, with sales falling 5% year-over-year (YOY) in constant currencies (down 6% as reported) to €1.7 billion (~$1.9 million). This is against a somewhat tough comparison, as sales rose 9% YOY as reported in 1Q15. Sequentially, Sanofi’s diabetes portfolio revenue fell 9%. As in past quarter, declining US sales drove the lion’s share of the overall sales decline. US sales fell 11% YOY in constant currencies (down 10% as reported) to €948 million (~$1.0 billion). In comparison, Sanofi’s diabetes portfolio performance was stronger in emerging markets (up 6% YOY in constant currencies to €331 million [~$365 million]) and in Europe (up 4% YOY in constant currencies to €338 million [~$372 million]). Sanofi shared that, excluding Venezuela, the diabetes portfolio actually grew by 12% YOY in emerging markets and management particularly highlighted a strong contribution from China. Sanofi’s combined diabetes and cardiovascular business unit performed slightly better in 1Q16, with sales falling 4% YOY in constant currencies (down 5% as reported). We expect the combined business unit’s performance will improve if and when sales of Sanofi/Regeneron’s PCSK9 inhibitor Praluent (alirocumab) ramp up.

Figure 1: Total Sanofi Diabetes Portfolio Sales (1Q05-1Q16)

Lantus (insulin glargine)

• Lantus (insulin glargine) sales fell 11% YOY in constant currencies (12% as reported) to €1.4 billion (~$1.5 billion). Sales declined 9% sequentially from €1.5 billion (~$1.7 billion). This was largely driven by the US, where Lantus revenue fell 18% in constant currencies (-16% as reported) to €843 million (~$930 million) from €1.0 billion (~$1.1 billion) in 1Q15.
• Management attributed this largely to a lower average net price for Lantus in 2016 compared to 2015. By volume, Sanofi emphasized that combined Lantus and Toujeo (U300 insulin glargine) total prescription (TRx) market share remains relatively stable at 68%. We imagine Sanofi may have been forced to accept high rebates in order to maintain broad access for Lantus in the face of increased pricing pressure and competition from Novo Nordisk’s next-generation basal insulin Tresiba (insulin degludec), which had a very strong first quarter on the US market in 1Q16.
• Lantus sales were also impacted in Europe, falling 4% YOY at constant exchange in 1Q16 (rising 6% as reported) to €236 (~$260 million). European Lantus sales were likely impacted by the rollout of Lilly/BI’s biosimilar insulin glargine Basaglar/Abasaglar there. According to Lilly’s 1Q16 update, the biosimilar is steadily growing its market share, though there is wide country-to-country variation. For instance, Abasaglar holds 17% of the market in Slovakia, where Lantus is not reimbursed well. On the other end of the spectrum, the product holds just 2% of the market in Germany. Sanofi management pointed out that the overall diabetes portfolio grew in Europe despite the competition from the biosimilar, however. In contrast to the US and European performance, Lantus sales in emerging markets rose 6% at constant exchange (falling 17% as reported, likely largely due to an extremely negative foreign exchange impact from Venezuela) to €228 million (~$251 million). Sanofi pointed to China and the Middle East as main drivers of this growth.

Figure 2: Lantus Sales (1Q05-1Q16)

Toujeo (U300 insulin glargine)

• Toujeo sales reached €103 million (~$114 million) in 1Q16, a nearly 15-fold increase compared to 1Q15, the product’s first quarter on the market. Sequentially, Toujeo sales grew 5% as reported, a marked slowdown from 2015, when sales approximately doubled each quarter. We imagine the long-awaited US launch of Novo Nordisk’s long-acting basal insulin Tresiba (insulin degludec) slowed Toujeo’s growth to some extent. According to Novo Nordisk’s 1Q16 update, Tresiba has already achieved 8% of the new-to-brand prescription (NBRx) market share in the US after one quarter on the market, compared to Toujeo’s 16% market share after a full year on the market. Indeed, US sales for Toujeo actually fell sequentially (by 1%) in 1Q16 to €78 million (~$86 million), from €79 million (~$87 million) in 4Q15. Ex-US sales rose 32% sequentially to €25 million (~$28 million) from €19 million (~$21 million) in 4Q15. Sanofi expects Toujeo to launch in over 40 countries by the end of 2016.

Figure 3: Toujeo Sales (1Q15-1Q16)

• The overall basal insulin analog market role 1% YOY as reported to $2.4 billion in 1Q16, up from $2.4 billion in 1Q15. Excluding Lantus, every product in the class (Toujeo, Novo Nordisk’s Levemir [insulin detemir], Novo Nordisk’s Tresiba [insulin degludec], and Lilly/BI’s Basaglar/Abasaglar [biosimilar insulin glargine]) experienced growth in 1Q16 (thought from a much lower base than Lantus). By value, Lantus continues to dominate the basal insulin analog market with 64% of the market share. Levemir holds 27% of the market share, Toujeo holds 5% of the market share, Tresiba holds 4% of the market share, and Basaglar holds 0.5% of the market share. For comparison, Lantus held 65% of the basal insulin analog market share by value in 4Q15.

Figure 4: Total Basal Insulin Market Sales (1Q06-1Q16)

Lyxumia (lixisenatide)

• GLP-1 agonist Lyxumia (lixisenatide) grew 13% at constant exchange and as reported to €9 million (~$10 million). That said, this encouraging double-digit growth occurred from a low base of just €8 million (~$9 million) in sales in 1Q15. Sequentially, Lyxumia sales fell 18% from €11 million (~$12 million) in 4Q15. Sanofi did not discuss Lyxumia’s performance in either its update call or its press release.

Figure 5: Lyxumia Sales (2Q13-1Q16)

• By value, the GLP-1 agonist class grew 26% YOY to $1.1 billion in 1Q16, though it fell 3% sequentially. Within the class, Trulicity held 13% of the market share by value. Novo Nordisk’s Victoza (liraglutide) continued to lead the class with 64% of the market share by value. Byetta (exenatide twice-daily) and Bydureon (exenatide once-weekly) held 6% and 13% market share, respectively, Tanzeum held 3%, and Lyxumia held 1%.

Figure 6: GLP-1 Agonist Sales (1Q06-1Q16)

Afrezza

• Sanofi did not mention inhaled insulin Afrezza in its call or in any of its financial materials. Sanofi announced that it would terminate its partnership with MannKind for Afrezza at the beginning of 1Q16 and the marketing rights for the product reverted to MannKind in April. The decision was likely motivated by Afrezza’s sluggish sales in the first year of its launch ($1-2 million each quarter of 2015). The slow ramp-up is likely partially attributable to onerous prescribing requirements for the product and MannKind has shared that it plans to re-launch the product with an updated, targeted marketing plan.

Praluent (alirocumab)

• Sales of Sanofi/Regeneron’s PCSK9 inhibitor Praluent (alirocumab) totaled €12 million (~$13 million) in 1Q16, a nearly 2.5-fold increase from 4Q15 sales of €5 million (~$6 million). Sanofi repeatedly emphasized that Praluent’s uptake has been limited by the administrative hurdles imposed by many payers on access. Sanofi shared that market research in the US and Germany suggests that physician awareness and acceptance of the PCSK9 inhibitor class is already quite high, but physicians often have to complete onerous administrative paperwork before their patients are granted access to Praluent. Sanofi feels that positive results from the ODYSSEY OUTCOMES trial (hopefully) demonstrating a cardiovascular risk reduction for Praluent will be a key factor in the product’s future success.
• Sanofi has completed a 50% interim analysis for futility for ODYSSEY OUTCOMES. The data monitoring committee reassuringly recommended that the trial continue with no changes. Management hopes to conduct a 75% interim analysis for futility and overwhelming efficacy in the second half of this year. Having the trial stopped early for overwhelming efficacy would be a big boon for Praluent and the PCSK9 inhibitor class as a whole. The estimated completion date on ClinicalTrials.gov is February 2018.
• In 2Q16, the company expects to file a 300 mg formulation of Praluent that supports once-monthly dosing. Management shared that US sales force materials for Praluent are focused on its flexible dosing options – currently, Praluent is offered in a 75 mg and a 150 mg dose, each dosed twice-monthly. In comparison, Amgen’s PCSK9 inhibitor Repatha offers once-monthly or twice-monthly dosing. This difference in how the doses are structured has been raised as one of the only differentiating factors between the two products and it looks like Sanofi’s looking to close the gap.

Other Financial Highlights

• Sales of Sanofi’s rapid-acting insulin analog Apidra (insulin glulisine) fell 3% YOY in constant currencies (down 7% as reported) to €85 million (~$94 million). This was against a tough comparison as sales of Apidra rose 21% in 1Q15. Sequentially, sales of Apidra fell 18% in 1Q16, following a tough comparison in 4Q15 when sales rose 18% sequentially.

Figure 7: Apidra Sales (1Q08-1Q16)

• The overall rapid-acting insulin analog market fell 7% YOY as reported and fell 21% sequentially to $1.4 billion in 1Q16. All three of the major rapid-acting insulins (Humalog, Novo Nordisk’s NovoLog/NovoRapid [insulin aspart], and Sanofi’s Apidra [insulin glulisine]) experienced YOY and sequential declines. By value, NovoLog still leads the rapid-acting insulin market with 49% of sales. Humalog revenue accounted for 44% of the market this quarter and Apidra sales made up 7% of the market. MannKind’s inhaled insulin Afrezza (formerly partnered with Sanofi) did not report sales for this quarter so it is not included in these calculations, but its sales were flat at $2 million each quarter of 2015 and it likely has a negligible impact on whole-market trends. The rapid-acting insulin market has been contracting for some time now as GLP-1 agonists grow in popularity as an option for basal insulin intensification. We expect the class may be revitalized to some extent with the entrance of new products on the horizon, including Novo Nordisk’s faster-acting insulin aspart, Lilly/Adocia’s BioChaperone insulin lispro, and Sanofi’s biosimilar insulin lispro, but we expect competition from the growing GLP-1 agonist and SGLT-2 inhibitor classes to remain an important factor.

Figure 8: Total Rapid-Acting Insulin Market (1Q06-1Q16)

• Sales of Sanofi’s human insulin Insuman were flat operationally (falling 3% YOY as reported) at €32 million (~$35 million) in 1Q16. Insuman sales in emerging markets drove the bulk of this growth – sales for the product rose 33% YOY in constant currencies (though falling 21% as reported) to €11 million (~$12 million). Sales in Europe, previously Insuman’s largest market, continued to decline in 1Q16. Sales fell 9% in constant currencies (rising 17% as reported) to €21 million (~$23 million). Sequentially, worldwide Insuman sales fell 16% as reported.

Figure 9: Insuman Sales (4Q12-1Q16)

• Sales of the sulfonylurea Amaryl (glimepiride) fell 5% YOY at constant exchange (falling 9% as reported) in 1Q16 to €88 million (~$97 million). Sequentially, Amaryl sales fell 6% from €94 million (~$104 million) in 4Q15.

Figure 10: Amaryl Sales (1Q05-1Q16)

• Sanofi’s BGM portfolio accrued revenue of €17 million (~$19 million) in 1Q16, up 6% operationally and as reported in 1Q16. Sanofi has been deprioritizing its BGM portfolio of late and did not even break out its BGM revenue in its 1Q16 net sales financial worksheet.

Pipeline Highlights

LixiLan (insulin glargine/lixisenatide)

• Sanofi expects US regulatory decisions for lixisenatide and LixiLan (lixisenatide/insulin glargine) in July and August 2016, respectively. Management also highlighted the FDA Advisory Committee meetings for the two products scheduled for May 25. The Advisory Committee voted 12-2 in favor of approval of LixiLan, though several committee members expressed concerns about the proposed delivery device (but ultimately decided that the benefits of the product outweighed the potential risks). We expect a positive FDA decision will be forthcoming.
• In Q&A, management suggested that LixiLan’s ability to address both fasting and prandial glucose could be a differentiating factor from Novo Nordisk’s Xultophy (insulin degludec/liraglutide). Indeed, we’ve heard commentators suggest that a short-acting GLP-1 agonist such as lixisenatide would be more appropriate than a long-acting GLP-1 agonist such as liraglutide for patients in need of insulin intensification to address postprandial glucose excursions. In addition, Sanofi management offered a reminder that both components of LixiLan have demonstrated cardiovascular safety (though not superiority) in the ELIXA trial for lixisenatide and the ORIGIN trial for insulin glargine. The implication was, though liraglutide demonstrated a cardioprotective benefit in LEADER, we have yet to see the cardiovascular outcome results for insulin degludec. This seems like a fairly weak point of differentiation, considering topline DEVOTE cardiovascular outcomes trial results for insulin degludec are expected by the end of the year and the FDA was clearly reassured enough by the interim results of the trial to approve the product.

Insulin Lispro Biosimilar

• Phase 3 results from the SORELLA 1 trial for Sanofi’s insulin lispro biosimilar SAR342434 were shared at ADA 2016. The results demonstrated similar A1c reductions, postprandial glucose reductions, hypoglycemia rates, weight gain, and adverse event rates with SAR342434 compared to Lilly’s Humalog (insulin lispro) in patients with type 1 diabetes. Insulin dosages were also comparable between the SAR342434-treated groups and the Humalog-treated group. We expect phase 3 data from SORELLA 2 in patients with type 2 diabetes will be available soon and will demonstrate similar comparability between SAR342434 and Humalog. While the product will not likely reach the market for at least another year, we imagine that there will be plenty of speculation around its price as it moves through the pipeline given the increasing frustration with price increases for Lilly’s Humalog (insulin lispro) and other rapid-acting insulin analogs in recent years.

Other Pipeline Highlights

• Sanofi has added long-acting insulin analog SAR440067/LAPSInsulin-115 – acquired from Hanmi – to its phase 1 pipeline. The company appears to only be investigating the candidate for type 2 diabetes at this point. The candidate is expected to support once-weekly dosing and Hanmi was also investigating a combination of LAPSInsulin-115 with long-acting phase 2 GLP-1 agonist efpeglenatide for a once-weekly fixed-ratio LAPSInsulin Combo. We’re excited to see Sanofi moving ahead with development of the long-acting insulin and hope to eventually see the combination added to its pipeline as well. The long-acting insulin market has lagged behind the development of once-weekly GLP-1 agonists (presumably due to the much more narrow therapeutic range for insulin and more complex dosing), though several players have once-weekly insulins in their development pipeline. Novo Nordisk recently completed phase 1 studies for its own long-acting insulin (LAI287). PhaseBio has a once-weekly insulin (PE0139) in phase 2a trials (phase 1 results presented at ADA 2016) and AntriaBio has a once-weekly basal insulin (AB101) in preclinical development.
• Management reiterated that it plans to advance the long-acting GLP-1 agonist efpeglenatide and the SGLT-1/2 dual inhibitor sotagliflozin into phase 3 for type 2 diabetes in 4Q16. Management first announced this timeline at JP Morgan. Sanofi licensed efpeglenatide from Hanmi in November along with the phase 1 once-weekly basal insulin LAPSInsulin-115 (SAR440067) and a preclinical combination of the two compounds. It licensed sotagliflozin from Lexicon less than a week later; that product is also in phase 3 for type 1 diabetes, and Lexicon retains exclusive rights to co-promote it for that indication. There were no new updates on the products during the 1Q16 update.
• Sanofi’s GLP-1/glucagon dual agonist SAR425899,  its GLP-1/GIP dual agonist SAR438335, and its stable glucagon SAR438544 remain in phase 1. Sanofi presented promising full phase 1 results for GLP-1/glucagon dual agonist SAR425899 at ADA 2016 (previously previewed at the Keystone Symposia on New Therapeutics for Diabetes and Obesity).

Questions and Answers

Q: Could you remind us of our strategy with lispro in the U.S. and potentially outside the U.S. as well?

A: Regarding the strategy for lispro, just be aware that actually the central strategy for Sanofi is to develop an integrated portfolio of products that can address the different needs of patients at different stages in their treatment journey. So, we want to be able to offer wide range of products and by bringing to market Sanofi's own insulin lispro, we would further reinforce our commitment to expanding the access to medication for diabetes patients. Our goal is to commercialize this product in geographies where we can achieve this objective. It would be a bit too premature to go into further details at this stage.

Q: Can you discuss any impact other biosimilars have on the market for Lantus in Japan? That was something that was called out by Novo in their call.

A: Yeah, sure. In Japan the biosimilars launched before our new insulin glargine Lantus XR, so our product launched at a significant discount and without the two-weeks prescription. The Japan market is the smallest of our three mature markets that we have. We launched our Lantus XR last September and it is gradually penetrating the market. However, it is still under the two week's limitation at this stage.

Q: I would like to hear about your view on LixiLan and Xultophy and the relative positioning of those given that we've had such strong data from LEADER. I would love to hear whether this data has made a difference because Victoza seems to be now much stronger compared to Lyxumia?

A: As I said earlier our company strategy is to have an integrated portfolio of products that can address the different needs of the patient throughout their journey. So, within this strategy, LixiLan is really well-positioned because it can be positioned as the first injectable that provides greater HbA1c control for patients initiating a basal therapy. It can also help with basal identification.

It is important to keep in mind that LixiLan would offer both fasting plasma glucose and post-prandial glucose control.

Now, regarding your question on the studies that have been conducted, I mean we cannot really comment on the LEADER study because the full results have not yet been presented. However, I would highlight that the study has been conducted in a population that was different from the population studied with ELIXA.

I also would like to remind you that with LixiLan, we also are very confident in the quality of the data submitted. When we evaluated the safety and efficacy of LixiLan, we included the outcomes of the LixiLan cardiovascular outcome trials (which ensured the cardiovascular safety) in our analysis. On the other side of the equation is Lantus’ ORIGIN study which is long-lasting and has a very large patient population that demonstrated the cardiovascular safety of the drug.

Q: Can you tell us a little bit more about your market positioning, market share, and market research of Praluent?

A: We’ve done market research with 100 specialists and 100 primary care physicians in the U.S. to just survey their attitude towards PCSK9, and, in general, and I must say the survey is completely aligned with the results and with our own concerns that eligible patients are not getting sufficient– if any– access to the drug. The three primary issues the market research raised are that (i) around 80% of cardiologists and primary care physicians felt that payer requirements created a very heavy burden for them and their office staff, (ii) about two-thirds of those physicians felt that they could not put every patient with medical needs under PCSK9 in a timely manner, and (iii) that two-thirds of PCPs felt they were facing a higher level of frustration with the payer restriction compared to other cardiovascular treatment and medicine.

Q: Looking at the basal insulin market, predominantly in the US, we now have Tresiba and Toujeo launched. We're seeing an interesting trend with Tresiba in terms of the dosing that's actually getting taken up. Can you just talk about which patients Toujeo is capturing, which patients Tresiba is capturing, and if you see any difference between the two groups that's going to last in the longer term?

A: To answer the question on the basal insulin in the US, Toujeo is–for us– the best product to serve a wide range of patients because its benefits are not limited to any type of patient.

I'll remind you that it's a profile with a flat PK/PD profile that actually serves all types of patients. We actually continue seeing the ramp up of Toujeo with a market share of 4.4%in the U.S. in the first quarter, which is 1.3 points over the fourth quarter of last year. I would also highlight that we continued to see a very nice increase of the prescription of Toujeo in the first quarter in the US.

Q: For Praluent, the interim that was just performed was based on, I believe, 50% of required events, and you're expecting the second interim in the second half this year. Just mathematically, can you actually get to 75%of the required events if you have only completed 50% given the patient flow?

A: For the first question, the answer is pretty straightforward. As you know, when we get 50% events, you have adjudicated them and it takes a while between the time you get an effective 50% and the time you get the analysis for futility and therefore we just did the analysis, but we're way beyond 50% now. And so I'm confident we can recruit what we need or that we can complete the event rate that we're expecting by the second half of this year.

Q: If I look at the Lantus US revenues for Q1 sequentially over Q4, the decline seems to be less severe than maybe it could have been coming out of Q4. So, are sales actually recovering a little bit, or is it just a shift between the quarters?

A: Yes, we have a minus 4.5% sales decline in Q1, which is actually minus 3.6% if you take Venezuela out. It's significantly less than the 12.6% negative we've seen in Q4. But the decline in Q4 was mainly driven by higher commercial rebates and an unfavorable channel mix towards government channels. We also faced delayed medical bills for Lantus. And we had a basis which was unfavorable for comparison because we had a Lantus price increase during the last quarter of2014. So for all those reasons, sales are much more favorable in Q1, which reflects of course what we have expected: a lower average net price versus last year. This decline is basically driven two-thirds by unfavorable channel mix and one-third by co-pay assistance and additional rebates. But we are reassured by our Q1 diabetes performance because it is right in our guidance.

Q: With diabetes, the long-term outlook has improved with the deals that you've done with Lexicon and Hanmi, but, despite Novo coming out CV benefits for their GLP-1 portfolio and the hyper-benefit for Tresiba over Lantus, are you basically saying that that has not changed your outlook for diabetes? I just want to clarify that's the case.

A: Related to diabetes, we are satisfied with our Q1 performance because it confirmed the previously issued guidance we expressed in October which was -4% to -8% over the period of 2015 to 2018.

Q:  The first question I have is on the PCSK9 litigation: can you give us your thoughts on the next steps and potential timelines of your appeal, request to retrial, injunction ruling and any potential settlement discussions?

Secondly, can you talk us through recent guideline updates on Praluent? How do you think they may change your ability to get payer access and how might the guidelines change again post-OUTCOMES data? And thirdly, on the Boehringer Ingelheim deal, you're still in negotiations, and is there are any reason to believe that any of the terms could look different from what you announced in December or is what was in the original press release pretty much set in stone? Additionally, can you help us understand why it takes quite so long to sign the deal and if there is any risk still that it might not happen?

A: As you know, the decision in March 2016 is only the first step in the litigation and we strongly disagree with the outcome of the lay jury trial. We will appeal that decision at the appropriate time. Right now, we are in what is known as a post-trial briefing period, which will go until May 25^th, at which point the judge will consider all that has been put before her and issue a decision. We don't believe that it will come very quickly. We believe it will be a couple of months. While in theory she could rule at any time, we firmly believe, given the nature of this trial, that it will take a few months before she ultimately issues something. At that point we will be in a position to appeal. And, again, we truly believe that the law and facts support our position of invalidity.

At the last ACC Congress, we were not yet at the step of the guidelines but we now have a very good first step that will happen before the new ACC guidelines. The Expert Consensus Decision Pathway was renewed and now considers the PCSK9 inhibitor in patients who are on maximal tolerated statins or secondary prevention as a second step to achieve their LDL reduction in the case of ASCVD and as an addition to ezetimibe when the LDL level is more than 190 milligrams.

This decision pathway recognizes the patient benefit groups by providing guidance to healthcare professionals as to when to begin treatment with a PCSK9 inhibitor. The decision pathway also clarifies that there are some groups of patients for which you can consider PCSK9 as a choice for an initial non-statin therapy in addition to maximally tolerated statin. I think this will help the healthcare physicians to actually navigate the environment as a choice of therapy.

So this is, as I said before, a first step before a new ACC guideline and I also would like to highlight that, in Europe, we also expecting new updated ESC guidelines in Q3 of this year.

Q: I want to ask about the €12 billion to €14 billion pipeline target across the six major product launches. Given the launch trajectory of Praluent, are there any changes in your expectations for that number, and are any of the products launching differently than expected?

A: We are not changing our long-term guidance regarding the combined peak sales of the six new launches; it’s still €12 billion to €14 billion combined peaks.

-- by Helen Gao, Sarah Wilkins, Emily Regier, and Kelly Close