CC - AACE 2016 Day #2 Highlights | Close Concerns Knowledgebase

Executive Highlights

We’re back with Day #2 of the American Association of Clinical Endocrinologists' 25th Annual Scientific and Clinical Congress. Thursday’s proceedings were headlined by ADA’s Dr. Robert Ratner, who argued that beta cell dysfunction is the root cause of all types of diabetes, an AZ-sponsored corporate symposium type 2 diabetes drugs, and a debate featuring Dr. Richard Pratley (Florida Hospital Diabetes Institute, Orlando, FL) and Dr. Alan Garber (Baylor College of Medicine, Houston, TX) on the relative merits of initial sequential vs. combination therapy for type 2 diabetes – we’ll be hearing more about this going forward as the priorities of cost, convenience (a proxy for adherence in the eyes of many), and getting patients on optimal therapy at the optimal time continue to be debated. Additional highlights included an obesity corporate symposium, where Dr. Timothy Garvey (University of Alabama, Birmingham, AL) noted that it is “a stretch” to generalize enthusiasm from recent positive CVOT findings in diabetes (EMPA-REG, LEADER) to obesity candidates, and Dr. Robert Kushner (Northwestern University, Chicago, IL) discussed techniques for communicating with patients about weight management. Many have expressed the need for more teaching on this topic in medical schools and other educational settings. Notably, the exhibit hall contained several notable pearls, including news that Animas plans to initiate its hypoglycemia-hyperglycemia minimizer study in June (well ahead of previous timing); an update from Tandem on t:sport (prototype to be displayed at ADA 2016) and its first-gen predictive low glucose suspend system (entering feasibility studies this summer); and Insulet’s navy blue rebranding and new unregulated app for support and ordering supplies. On the drug side, Novo Nordisk dominated the exhibit hall with three booths featuring new basal insulin Tresiba and their other insulins as well as Saxenda and obesity education. See below for our top five highlights and honorable mention from the day, followed by our detailed coverage.

Check out our preview to see what we’re looking forward to tomorrow, and check out our Day #1 coverage, if you missed it yesterday!

1. In a packed session that still felt intimate, Dr. Robert Ratner (ADA, Alexandria, VA) argued that beta cell dysfunction is the root cause of all types of diabetes and that type 2 diabetes progression can be prevented with appropriate protection of the beta cell.

2. An AZ-sponsored corporate symposium touched on a number of hot-button issues related to new type 2 diabetes drugs, including hypoglycemia, weight, side effects, and cardiovascular risk reduction.

5. The exhibit hall contained several notable tech updates, including news that Animas plans to initiate its hypoglycemia-hyperglycemia minimizer study in June (well ahead of previous timing – great news to hear), an update from Tandem on t:sport and its first-gen predictive low glucose suspend system, and Insulet’s navy blue rebranding and new unregulated app for support and ordering supplies. See below for additional updates from Novo Nordisk, Lilly, Medtronic, and more!

Honorable Mention: Dr. George Dailey (Scripps Whittier Diabetes Institute, La Jolla, CA) led a well-attended Sanofi product theater on Toujeo (insulin glargine U300), discussing the benefits of the product vs. Lantus (insulin glargine U100) and sharing a new estimate that “500,000 prescriptions have been written in the first year.” We hadn’t heard that statistic before.

Top Five Highlights

1. In a packed session, Dr. Robert Ratner (ADA, Alexandria, VA) argued that beta cell dysfunction is the root cause of all types of diabetes and that type 2 diabetes progression can be prevented with appropriate protection of the beta cell. He argued that factors such as insulin resistance, relative insulin deficiency, and multi-organ defects are not sufficient to define type 2 diabetes and its cause. Instead, he suggested that all types of diabetes – type 1, type 2, LADA, etc. – occur when the beta cell is “unable to keep up” for some reason. By this definition, the line between type 1 and type 2 diabetes blurs – in fact, audience member Dr. Stanley Schwartz (University of Pennsylvania, Philadelphia, PA) went so far as to suggest that categorizing people as type 1 or type 2 has lost its relevance and that diabetes diagnosis should be based on the source of beta cell dysfunction and how much residual function is available. This was pretty interesting. In this session, Dr. Ratner shared that the ADA, AACE, and JDRF will publish a joint statement on defining the natural progression of diabetes in August, though he emphasized that the terms of type 1 and type 2 diabetes have become too entrenched to do away with entirely. Dr. Ratner highlighted data from the ORIGIN trial in which targeting a fasting glucose of 95 mg/dl was able to prevent progression of type 2 diabetes and progression from prediabetes to type 2 diabetes in over 12,000 patients over seven years. The key here, according to Dr. Ratner, was the aggressive fasting glucose target. He suggested that glucotoxicity actually occurs at fasting glucose levels around 120 mg/dl, rather than the conventional threshold of 300 mg/dl, and that even these close-to-normal levels of glucose are sufficient to stress the beta cell and cause progressive dysfunction. Dr. Ratner emphasized that much more research into the natural history and progression of beta cell function and dysfunction are needed, especially at the early stages of diabetes. Given the current understanding, however, Dr. Ratner asserted that “protecting the beta cell in any way you can is obviously the solution to diabetes.” We salute Dr. Ratner for all the learning he enables and his major commitment to teaching.

See the detailed discussion section below for many more thoughts from Dr. Ratner, including commentary on the study design for Dr. Ralph DeFronzo’s triple therapy study and a “rant” on how the significance of microvascular complications is often dismissed.

2. An AZ-sponsored corporate symposium touched on a number of hot-button issues related to new type 2 diabetes drugs, including hypoglycemia, weight, side effects, and cardiovascular risk reduction.

Dr. Lawrence Blonde (Ochsner Health System, New Orleans, LA) highlighted the importance of hypoglycemia in type 2 diabetes and the ability of newer agents to reduce this risk. Dr. Blonde particularly celebrated the availability of new alternatives to prandial insulin that carry a lower risk of hypoglycemia – a very relevant discussion with two GLP-1 agonist/basal insulin combinations likely headed for approval. We were moved that he gave a shout-out to the issue of glycemic variability during the discussion following his talk, noting that patients who experience less variability after adding a GLP-1 agonist to basal insulin instead of adding prandial insulin report improvements in treatment satisfaction, perceived health, and quality of life. We are very heartened to see more attention paid to a broader group of outcomes.
Dr. Luigi Meneghini (UT Southwestern and Parkland, Dallas, TX) reviewed the whole menu of potential adverse effects associated with newer drug classes and framed some specific concerns in selected populations. He suggested that the incretin-pancreatitis controversy has largely been put to rest by post-marketing surveillance and CVOT data, though he emphasized that the drugs should still be used with caution in patients at high risk for pancreatitis. On the recent issue of rare but severe joint pain with DPP-4 inhibitors, he argued that it is difficult to get a good sense of the true frequency from post-marketing reports and that clinicians prescribing these drugs should be aware and prepared for this potential side effect. With SGLT-2 inhibitors, he suggested that it is important to educate patients about the risk of serious UTIs and bone fractures, especially in older patients, and ketoacidosis in those with insulin deficiency, but he believes these risks are typically manageable and outweighed by the benefits in many patients.
Dr. Vivian Fonseca (Tulane University, New Orleans, LA) suggested that the incoming wealth of CV outcomes data for diabetes drugs could be very useful for personalizing therapy. Just based on currently available results, one might choose to prescribe TZD pioglitazone in patients with a history of stroke (though there will be concerns about weight gain and edema), SGLT-2 empagliflozin in those at risk for heart failure, and a GLP-1 agonist in the setting of multiple atherosclerotic defects. There was some discussion following his talk about the generalizability of the EMPA-REG OUTCOME results and the enormous importance of trial design – Dr. Pratley suggested that the trial design and population can be as important as the drug itself in determining results and of course we know this is true – the EMPA data was on a sicker population so it will be interesting to hear how generalizable the results will be, if at all. This will be important to top of mind as SGLT-2 inhibitor and GLP-1 agonist CVOTs continue to report – it is of course not so surprising that the empa trial finished first, given how sick the patients were.

3. Dr. Richard Pratley (Florida Hospital Diabetes Institute, Orlando, FL) and Dr. Alan Garber (Baylor College of Medicine, Houston, TX) debated the relative merits of initial sequential vs. combination therapy for type 2 diabetes, though both agreed that clinical inertia remains a major concern. Dr. Pratley argued that prompt sequential therapy is often preferable to initial combination therapy in patients with moderately elevated A1cs (7.5%-9%), though he agreed that multiple agents are needed for those with very poor control. He noted that a substantial percentage of patients do reach their A1c targets with one agent initially and argued that the hope of synergistic efficacy with approaches like DPP-4 inhibitor/SGLT-2 inhibitor combinations has not been realized. Other arguments against initial combination therapy included (i) lack of comparative efficacy data on different combinations; (ii) decreased dosing flexibility with fixed-dose combinations; (iii) difficulty determining the source of side effects; (iv) decreased adherence due to pill burden; (v) cost; and (vi) lack of insurance coverage. Arguing in favor of initial combination therapy, Dr. Garber emphasized that combination therapy has beaten monotherapy in terms of efficacy every time it has been studied, often with a dose-sparing effect. He also argued that Dr. Pratley’s ideal of rapid sequential therapy rarely occurs in real-world practice, pointing to a Kaiser study showing that patients typically spend 36 months with an A1c >8% before a second drug is added. He suggested that much of this inertia comes from patients as well as physicians, noting that many of his patients view the prescription of a second drug as a punishment. We were a bit troubled to hear that he perceives “many” patients as feeling this way and believe that is strongly influenced by how the physicians educates the patient beforehand. While we are sympathetic to Dr. Pratley’s arguments, particularly his points on cost, side effects, and pill burden, we thought Dr. Garber’s point about clinical inertia in current practice was ultimately the most relevant argument – we see initial therapy with fixed-dose combinations of well-tolerated drugs as an excellent option for many patients.

In an evening corporate symposium, Dr. Pratley took a slightly different tack and referred to GLP-1 agonist/basal insulin combinations as “a significant introduction of a new treatment paradigm.” He highlighted the improved glycemic control, lower risk of hypoglycemia, weight loss, and lower doses of insulin associated with the combinations. He also noted that the slow titration of the GLP-1 agonist with the combination results in less nausea than standalone GLP-1 agonist therapy. He also suggested that the copays for the new combinations could be lower than the two copays for the products independently. Overall, Dr. Pratley expressed excitement over the FDA Advisory Committee’s recent votes in favor of approval of Novo Nordisk’s Xultophy (insulin degludec/liraglutide) and Sanofi’s LixiLan (lixisenatide/insulin glargine).

4. In response to a question during an evening corporate symposium, Dr. Timothy Garvey (University of Alabama, Birmingham, AL) said that it is “a stretch” to generalize enthusiasm from recent positive CVOT findings in diabetes (EMPA-REG, LEADER) to obesity candidates. The discussion focused primarily on the potential implications of LEADER on Saxenda (liraglutide 3.0 mg), and Dr. Garvey was quick to point out that differences in dose (1.8 mg vs. 3.0 mg) and study population (diabetes vs. non-diabetes) makes extrapolation of the results nearly impossible. Dr. Garvey did suggest that other data – such as the Swedish Obesity and Da Qing studies – do offer some evidence that weight loss offers a morality benefit though stressed that we need to wait for ongoing obesity CVOTs to report before making firm conclusions. Notably, he was also pressed on the potential implications of EMPA-REG in obesity – to which he even more firmly reminded attendees that there is little mechanistic basic to extend diabetes CVOT findings (especially in other drug classes) to those in obesity – though we thought the question spoke to the way in which recent positive results have generated an optimism around outcomes trials that was absent pre-EASD 2015. Indeed, the enthusiasm reminded us that EMPA-REG revealed an unexpected and clinically meaningful benefit that may be overshadowing some of the still valid critiques of the current approach. For this reason, we appreciate Dr. Garvey’s balanced take and hope to see similar nuanced discussion in the coming years to ensure that both diabetes and obesity CVOTs are answering the most relevant clinical questions.

In the same symposium, Dr. Robert Kushner (Northwestern University, Chicago, IL) discussed techniques for communicating with patients about weight management, with a focus on language and the importance of demonstrating empathy when discussing weight with patients. He suggested that the “5 A’s” (Ask, Assess, Advise, Agree, Assist) and motivational interviewing can provide a framework for obesity conversations and advocated for open-ended questions and shared decision-making that is more likely to elicit behavioral changes in patients. He urged providers to be proactive in discussions surrounding weight and presented NHANES data demonstrating that individuals were more likely to be successful with their weight-loss goals if their doctor brought up their weight. Ultimately, we appreciated Dr. Kushner’s recommendations for weight loss communication – certainly, change is needed in our social approach to obesity.

5. The exhibit hall contained several notable pearls, including news that Animas plans to initiate its hypoglycemia-hyperglycemia minimizer study in June (well ahead of previous timing); an update from Tandem on t:sport (prototype to be displayed at ADA 2016) and its first-gen predictive low glucose suspend system (entering feasibility studies this summer); and Insulet’s navy blue rebranding and new unregulated app for support and ordering supplies. On the drug side, Novo Nordisk dominated the exhibit hall with three booths featuring Saxenda, obesity education, and diabetes drugs. See below for our exhibit hall coverage of Abbott, Dexcom, Lilly, Medtronic, Sanofi, and more!

Honorable Mention: Dr. George Dailey (Scripps Whittier Diabetes Institute, La Jolla, CA) led a relatively well-attended Sanofi product theater on Toujeo (insulin glargine U300), discussing the benefits of the product vs. Lantus (insulin glargine U100) and sharing a new estimate that “500,000 prescriptions have been written in the first year.” This is the first time we have heard the latter, and it provides some context to the figures Sanofi typically presents at its financial updates – in 4Q15, management shared that Toujeo’s new-to-brand prescription market share had stabilized at 13.5%-15%, with total prescriptions ramping up to above 4%. More broadly, Dr. Dailey spent the majority of the session discussing the barriers to initiating insulin in people with type 2 diabetes before introducing Toujeo’s pharmacology, clinical data, and dosing and administration. He walked through different case studies, demonstrating how to dose the product for a wide range of patients, from insulin-naïve patients to those on basal-bolus therapy. Dr. Dailey emphasized Toujeo’s smaller volume and compact depot size, pointing to its gradual release and steady state. He acknowledged the FDA’s decision to exclude Toujeo’s nocturnal hypoglycemia data from the agent’s label but also pointed to meta-analyses that have demonstrated statistically significant reductions in nocturnal hypoglycemia. We were struck by his confidence on the degree of Toujeo’s hypoglycemia benefit in type 2 patients, and when pressed in Q&A on the benefit of Toujeo vs. Lantus, Dr. Dailey stressed that “the reduction in hypoglycemia is one of the big advantages!”

Detailed Discussion and Commentary

Meet The Professor

Is Insulin Therapy Inevitable in the Management of Diabetes?

Robert Ratner, MD (ADA, Alexandria,VA)

In a packed but intimate session, Dr. Robert Ratner (ADA, Alexandria, VA) argued that beta cell dysfunction is the root cause of all types of diabetes and that type 2 diabetes progression can be prevented with appropriate protection of the beta cell. He argued that factors such as insulin resistance, relative insulin deficiency, and multi-organ defects are not sufficient to define type 2 diabetes and its cause. Instead, he suggested that all types of diabetes – type 1, type 2, LADA, etc. – occur when the beta cell is “unable to keep up” for some reason. By this definition, the line between type 1 and type 2 diabetes blurs – in fact, audience member Dr. Stanley Schwartz (University of Pennsylvania, Philadelphia, PA) went so far as to suggest that categorizing people as type 1 or type 2 has lost its relevance and that diabetes diagnosis should be based on the source of beta cell dysfunction and how much residual function is available. Dr. Ratner shared that the ADA, AACE, and JDRF will publish a joint statement on defining the natural progression of diabetes in August, though he emphasized that the terms of type 1 and type 2 diabetes have become too entrenched to do away with entirely. Dr. Ratner highlighted data from the ORIGIN trial in which targeting a fasting glucose of 95 mg/dl was able to prevent progression of type 2 diabetes and progression from prediabetes to type 2 diabetes in over 12,000 patients over seven years. The key here, according to Dr. Ratner, was the aggressive fasting glucose target. He suggested that glucotoxicity actually occurs at fasting glucose levels around 120 mg/dl, rather than the conventional threshold of 300 mg/dl, and that even these close-to-normal levels of glucose are sufficient to stress the beta cell and cause progressive dysfunction. Dr. Ratner emphasized that much more research into the natural history and progression of beta cell function and dysfunction are needed, especially at the early stages of diabetes. Given the current understanding, however, Dr. Ratner asserted that “protecting the beta cell in any way you can is obviously the solution to diabetes.”

Dr. Ratner controversially suggested that Dr. Ralph DeFronzo’s triple therapy study design is “somewhat problematic.” Several audience members – “DeFronzo fans,” as Dr. Ratner called them – suggested that initial combination therapy can prevent the progression of type 2 diabetes. Dr. Ratner acknowledged that Dr. DeFronzo’s logic of easing the burden on the beta cell to protect it and prevent further stress may indeed have merit, but suggested that his study design has raised questions about his data that may explain why his approach isn’t more widely practiced. He did not elaborate further, but the comment could perhaps refer to the fact that the two groups are being treated with different drug combinations as well as different administration schedules (metformin+pioglitazone+exenatide administered in combination vs. metformin, glipizide, and insulin glargine administered sequentially), potentially confounding the results.
Dr. Ratner suggested that the use of glucose as a biomarker for diabetes is essentially based on coincidence and convenience. He submitted that the only reason we define diabetes by glucose is because ants were attracted by elevated urine glucose 2,000 years ago. He also noted that glucose is easy to detect and measure in the blood, unlike potential other biomarkers such as free fatty acids or lipids, resulting in our reliance on blood glucose and A1c levels to diagnose diabetes today.
Dr. Ratner “ranted” about how the significance of the microvascular complications of diabetes is often dismissed – as patients, we are so glad to hear his emphatic words on this front. He reminded attendees that hospital wards used to be filled with patients waiting for kidney transplants, amputees, and patients with varying degrees of retinopathy. Although the incidence of a number of macrovascular and microvascular complications of diabetes has decreased significantly in the last 15 years, there are a far higher number of patients now at risk. However, Dr. Ratner suggested that we may be a “victim of our own success” and objected to the USPTF guidelines’ implication that preventing diabetes is now worthwhile only because diabetes is a risk factor for cardiovascular disease (we had not heard this characterization of USPTF in as much detail before). He emphasized that many, many patients still face debilitating microvascular and macrovascular complications from diabetes and criticized the notion that diabetes is not an extremely serious disease in and of itself. While we believe USPTF would ultimately agree with us, public attitudes are of course so critical and we would love to see more emphasis on this front as well as on prevention.
Dr. Ratner shared that Dr. Silvio Inzucchi will be presenting data on the progression of patients with prediabetes to type 2 diabetes in the IRIS trial at ADA 2016, hinting that there is much more compelling data than what was published. The IRIS trial found that pioglitazone therapy is associated with a reduced risk of progression to type 2 diabetes, stroke, and MI in a population of patients with prediabetes and a previous history of stroke or transient ischemic attack (TIA). The IRIS trial is one of the more intriguing studies of potential medications for prediabetes and we’ll be curious if the data could encourage more providers to prescribe pioglitazone for prediabetes or even lead to a label indication. The use of medications in prediabetes is still relatively controversial, but we’d imagine that at least some very-high risk individuals would benefit greatly from additional options beyond lifestyle therapy. We’ll certainly be listening closely to this presentation at ADA!

Exhibit Hall

Abbott

Abbott’s yellow signage drew our attention as we approached the middle of the exhibit hall. The relatively large booth focused on the company’s FreeStyle InsuLinx product line. As expected, representatives did not offer any commentary on the timing of FreeStyle Libre in the US, and could not even share whether attendees had approached the booth asking about Libre! As a reminder, FreeStyle Libre Pro is slated for a mid-2016 US launch (submitted in 2Q15), while management said last year that the consumer version “optimistically” could be approved in time for an end of 2016 launch (we’re not sure if it is even at FDA yet). We hope to hear an update at ADA where the company’s Sunday night corporate symposia will include results from the six-month outcomes study in type 1s: IMPACT (n=225 type 1s on MDI or pumps, A1c <7.5%).

Amgen

Amgen’s modestly-sized booth was entirely devoted to its PCSK9 inhibitor Repatha (evolocumab). The booth was largely focused on the label and indicted population for Repatha. In what appeared to be a direct jab at Sanofi/Regeneron’s PCSK9 inhibitor Praluent (alirocumab), signage boasted that Repatha offers maximum efficacy at the start (whereas Praluent is offered in low-dose and high-dose formulations).

AstraZeneca

AZ’s Fit2Me food truck made a reappearance, showcasing healthy snacks based on recipes from the company’s Fit2Me patient support program. While sipping on a berry smoothie, we toured the company’s green-and-purple themed booth that featured screens spotlighting Farxiga (dapagliflozin), Onglyza (saxagliptin), Kombiglyze XR (saxagliptin/metformin), Xigduo XR (dapagliflozin/metformin), Byetta (exenatide twice-daily), and Bydureon (exenatide once-weekly).

Dexcom

Dexcom’s mid-sized booth was placed near the center of the exhibit hall. The booth focused on the Dexcom G5 mobile and paired iPhone and Apple Watch apps – a glass case sitting front and center of the booth showed the real things up close. Dexcom still expects to launch an Android version of G5 in 2016, supporting the major Android phone brands. The regulatory process here is more difficult than iOS, as there are so many Android phones to test. There were no updates on the plans to launch a new touchscreen receiver (2Q16 FDA submission), or the one-button insertion system and accompanying smaller transmitter (FDA submission in preparation as of 1Q16). Representatives did comment briefly on yesterday’s news that Medtronic and Qualcomm are partnering to develop a next-gen professional CGM for type 2 diabetes, heralding the partnership as an “exciting” step forward for the field and noting that “more noise around CGM is inevitably a good thing.” We certainly agree! A rising tide lifts all boats, especially in CGM where the market is still very underpenetrated in type 1 (though more recent growth has been great to see) and virtually non-existent in type 2. Reps did not comment on the insulin dosing label claim, which will have an FDA panel meeting on July 21 – we’re sure there is little they can say at this point.

Eisai

Eisai’s booth was almost entirely devoted to a product for thyroid cancer – its Arena-partnered obesity therapy Belviq (lorcaserin) was relegated to the back of the booth, and the Eisai representatives were much more eager to discuss the thyroid cancer drug. The small square footage devoted to Belviq signage emphasized that many different patients with the same goal of weight loss benefit from the product.

Insulet

Insulet’s mid-sized booth showed off the company’s navy blue new branding, complete with the redesigned OmniPod logo and images from the recently launched website, and unregulated app for support and ordering supplies (five reviews, five stars). The rebrand looks terrific and very fresh, giving the OmniPod way more of a consumer feel – “I’m always connected, but never tethered.” The OmniPod logo now features a blue circle (for diabetes) with 72 different lines, symbolizing 72-hour wear. Insulet now calls its customers “podders,” with a page dedicated to success stories – we expect to see lots more activity on social media. Reps confirmed plans to initiate automated insulin delivery (AID) system clinical trials later this year, and discussed goals to supplement PDM hardware functions with smartphone apps in future pump models. As we heard during Insulet’s 1Q16 financial update, the company expects to bring its AID product to market in “late 2018”, and anticipates it will include a Bluetooth-enabled pod and mobile connectivity. The company is still in FDA discussions about insulin dosing from a smartphone phone app, so we’re not sure what the ultimate artificial pancreas architecture could look like. In the meantime, Insulet plans to submit a 510(k) for its next-gen Bluetooth-enabled PDM and mobile app “later this year” – the app will display key real-time pump data on the phone AND integrate with Dexcom’s G5 app. Insulet just started on Twitter the other day under @myomnipod – great to see companies reaching out to patients in this way.

Intarcia

Intarcia’s small booth featured the company’s standard demonstration of the insertion and removal procedures for ITCA 650 (implantable exenatide mini-pump). Dr. John Yee, Intarcia’s recently appointed Head of Global Medical Affairs, Safety, and Operations, indicated that the company is actively preparing to submit ITCA 650 to the FDA. He did not have any insight on whether an AdComm would be required for the product – he noted that both the device and the drug have been previously approved, but we imagine that an AdComm might be likely given that this type of treatment is unprecedented in diabetes and given that FDA has required Ad Comms for most drugs of late.

J&J

J&J’s sizable booth was dedicated largely to Invokana, with Animas and LifeScan taking up just a small sliver of real estate at the back edge of the exhibit. A rep shared that Animas plans to start a “very large” clinical trial for the hypoglycemia-hyperglycemia minimizer (HHM) likely in June – this is well ahead of the timing shared in the Medical Device Business Review last week, calling for a pivotal to start “before the end of the year.” It’s great to see this finally moving and puts the company on track to hit the new timing to launch in the next 18 months. It will be fascinating to see how large and long this trial will be compared to the MiniMed 670G pivotal: n=124 completers, three month, single arm. We caught a picture of the new J&J/Dexcom device last week, which resembles the Vibe but oriented vertically with a color screen. Reps could not comment further on other pipeline updates, but expressed excitement for undisclosed “behind the scenes” developments at J&J; many must be excited internally about the OneTouch Via on-demand mealtime insulin delivery device (previously Calibra’s Finesse). As we learned during J&J’s Medical Device Business review last week, the company is planning a regulatory filing for the device in 2H16, with an expected launch by May 2016.

Lilly

Lilly’s vast, spacious booth lured attendees in with the promise of fresh-baked coconut macaroons and bright signage. In a departure from the company’s signature red theme prevalent in the rest of the booth, one corner was bathed in teal matching the teal body of the new Humulin U500 KwikPen – signage emphasized the easy dosing of high doses of insulin with no need for complicated dose conversions. GLP-1 agonist Trulicity [dulaglutide] dominated another significant section of the booth with multiple pens available for hands-on demonstration and slogans boasting the A1c efficacy, once-weekly dosing, and easy-to-use pen of the product. A wall devoted to the BI-partnered Jardiance (empagliflozin) and Synjardy (empagliflozin/metformin) invited attendees to ask booth representatives for more information on the product. A representative cryptically hinted that “there is a lot of buzz around Jardiance, but we can’t talk about it” – we assume he was referring to the EMPA-REG OUTCOME results demonstrating a cardioprotective benefit for the drug. Lilly/BI are hoping for an expanded indication for Jardiance and Synjardy reflecting the data, after which they’ll be free to highlight it as much as they’d like in their exhibits and marketing. The booth also showcase catchy slogans for Glyxambi (empagliflozin/linagliptin; “Duel inhibition ready for action”) and Tradjenta/Jenatdueto (linagliptin, linagliptin/metformin; “Help your patients navigate the road ahead”). Tying its diverse array of products together, Lilly featured a section devoted to the “ominous octet” of multiple organ defects in type 2 diabetes and how each of its drug classes can impact different organs.

Medtronic

Medtronic’s small booth advertised the MiniMed 530G, and reps were very excited to talk us through the details of the threshold suspend system. We picked up no new insights on the increasingly deep pipeline, and reps could not comment on yesterday’s partnership with Qualcomm to develop a next-gen professional CGM for type 2 diabetes. Reps did not say anything about the MiniMed 670G/Enlite 3 hybrid closed loop system, but we’ll see the pivotal data at ADA and an FDA submission before the end of June. We didn’t get any timeline update on the EU launch of the Guardian Connect standalone mobile CGM (a competitor to Dexcom’s G5), though we assume the previous timeline to launch ~May-July this year has not changed. As a reminder, this product was submitted to the FDA in March, putting it on track to hit the April 2017 launch timeline.

Merck

The small, bright Merck booth offered tempting frozen yogurt and even more tempting clinical data on Januvia (sitagliptin) and Janumet (sitagliptin/metformin). Booth representatives mostly emphasized the company’s Pneumovax vaccine for pneumococcal polysaccharide, however, urging physicians to have their patients with diabetes vaccinated.

Novo Nordisk

Novo Nordisk’s main booth was almost entirely devoted to Tresiba (insulin degludec) – the , though market-leading GLP-1 agonist Victoza (liraglutide) also had a small presence. This laser focus was reminiscent of the company’s displays at EASD and ENDO – it is clear where Novo believes its future success lies. The Tresiba displays emphasized the product’s long duration of action and dosing flexibility, and demo stations with the new pen were set up around the booth. A representative did not have information on whether the U100 or U200 formulation of Tresiba had been more popular so far, or whether most of Tresiba’s patient base consisted of switches or patients new to insulin. In the company’s 1Q16 update, management indicated that two-thirds of Tresiba prescriptions were for the U200 formulation, which has been more heavily promoted.

As at many recent conferences, Novo Nordisk had a separate booth focused on obesity drug Saxenda (liraglutide 3.0 mg) centered around huge models of the pen and featuring an image of a woman holding up a large pair of jeans with comorbidities written over them. A representative indicated that about half of the physicians he had spoken to today were actively diagnosing and treating obesity as a disease - that is higher than we expected, but he also noted that many do not have the resources to do so. He also noted that many providers treating patients with both obesity and type 2 diabetes will start treatment with Victoza and then switch to Saxenda once the patient’s A1c has come down a bit. We have been very curious since Saxenda’s approval how providers would navigate the likely overlap between the indicated populations for the two products, and we see this as a workable solution. In terms of the company’s promotional strategy, he indicated that the current target population is mostly patients with a BMI >35 who are “trying and failing” and those with severe obesity who are interested in bariatric surgery.

Novo Nordisk – Obesity

In addition to its two product-focused booths, Novo Nordisk also featured a small booth focused more generally on obesity education. Headlined with the slogan “rethink obesity,” the booth aimed to get the word out to providers about treating obesity as a disease, including by handing out posters to display in waiting rooms. The representative was fairly optimistic about the trend in this area, noting that more and more providers are thinking of obesity as a disease now that there are more tools to treat it.

Sanofi

Sanofi’s booth was anchored with giant, five-foot-tall SoloStar pens for Toujeo (U300 insulin glargine), Lantus (insulin glargine), and Apidra (insulin glulisine). About half of the square footage of the booth was devoted to Toujeo and booth representatives emphasized the product’s longer profile of action, less weight gain, and lower rate of severe hypoglycemia. Sanofi also emphasized the ease of switching from Lantus to Toujeo and highlighted the Toujeo COACH patient support programs and the prescription assistance programs. In a separate booth, Sanofi offered an educational quiz (“Are you a glycemic explorer?”) that shared shocking statistics about clinical inertia and the many, many drugs that have been approved since 2000 (29!). The activity culminated in information about how different drug classes affect different organs that contribute to type 2 diabetes pathophysiology – the booth representative especially emphasized the many complementary organs targeted by GLP-1 agonists and insulin. While the activity was not explicitly promoting any single product, we look forward to seeing what the marketing looks like for upcoming GLP-1 agonist/basal insulin combination LixiLan (lixisenatide/insulin glargine) as well as for Novo Nordisk’s IDegLira, once they are approved.

Sanofi/Regeneron

Sanofi/Regeneron’s booth offered a wealth of slogans for PCSK9 inhibitor Praluent (alirocumab): “The fall of high cholesterol,” “Redefining possible,” “Do you have patients ready to take the plunge?” Sanofi also highlighted a new direct-to-consumer campaign for Praluent, sharing that patients can now “dive into details of Praluent in their favorite magazines.” Building on the plunge and dive theme, the booth’s blue, green, and purple coloring evoked a whimsical aquatic landscape.

Tandem

Tandem’s characteristically modest exhibit showcased the company’s sleek portfolio of insulin pumps: the original t:slim, the Dexcom-integrated t:slim G4, and the 480-unit t:flex. Reps shared that Tandem has received an IDE to enter feasibility studies for the first-gen predictive low glucose suspend system this summer. We expect this means the company is still on track to start a pivotal trial by the end of 2016, with a commercial launch by the end of 2017 – that timing sounds very tight to us, but potentially doable if a lot of thing go well. Tandem could be second or third to market (after Medtronic or Animas), though it’s first-gen device will only predictively suspend insulin, not increase it. Reps also noted that Tandem’s ADA booth will display a prototype for t:sport, the company’s wearable patch pump prototype that was resurrected in 4Q15 (first shown at JPM 2013). The product includes an ~50% smaller t:slim worn on the body, a short infusion set, and pump control via a wireless handheld or mobile app. As of 4Q15, an FDA submission was expected in 2017. We look forward to seeing how the landscape evolves in the coming years, as many of Tandem’s competitors have patch pumps or patch-like insulin delivery devices in the works: J&J (OneTouch Via [formerly Finesse]), Medtronic (patch pumps reportedly in development), and Roche (Solo reportedly still in development). Of course, Insulet’s established OmniPod will be a formidable competitor for t:slim, especially as the company moves to revamp the system through a Bluetooth-enabled PDM and mobile app. Tandem reps also highlighted a banner on patient choice at the corner of the booth, alluding to UnitedHealthcare’s recent selection of Medtronic as its “preferred” provider of insulin pumps. This won’t have a crippling impact on Tandem’s overall business (~1,200 of 15,500 pumps shipped in 2015 would fall under this policy), but it is a competitive headwind and a serious threat if more payers go this route.

Valeritas

In a small booth on the edge of the exhibit hall, Valeritas’ showed off its simple disposable V-Go patch delivery device. Company reps were not able to comment on “V-Go Link” – the connected device featured on the Valeritas website and April investor presentation – though they did confirm that “V-Go Pre-Fill” is in development. They also highlighted the possibility of future use of V-Go to dose drugs in other disease states. As a reminder, Valeritas raised $24 million earlier this month in an alternative public offering.

-- by Helen Gao, Varun Iyengar, Emily Regier, Ava Runge, and Kelly Close

May 25-29, 2016; Orlando, FL – Day #2 Highlights – Draft