Howdy again from Austin! We’re here for the 26th annual AACE scientific and clinical congress – with this report, we bring you our top takeaways from day #2. See below for learnings on CGM education, outcomes beyond A1c, the new class of basal insulin/GLP-1 combos, insulin initiation in type 2, precision medicine for diabetes, and much more. When we weren’t in sessions with some incredible thought leaders (Drs. Anne Peters, George Grunberger, William Tamborlane, Judith Fradkin, and the list goes on…), we visited the spectacular AACE exhibit hall. This document includes our coverage of 16 booths from A-to-V, Abbott to Valeritas, and everything (alphabetically) in between.
Top 10 Highlights
1. A 5 AM Dexcom-sponsored symposium featured countless pearls on CGM education, the psychology of reacting to trends, reimbursement, outcomes beyond A1c, and more from Drs. George Grunberger, Anne Peters, and Kathleen Wyne. We’ve included quotable quotes below.
2. In an aptly-titled “Meet the Experts” session, DreaMed’s Dr. Moshe Phillip shared that the clinician-facing Advisor Pro decision support system will enter a pivotal study “toward the end of July/early August.” The trial is supported by the Helmsley Charitable Trust and will bring long-needed software for clinicians to optimize insulin therapy.
3. In an AZ-sponsored corporate symposium on the connection between diabetes, diabetes therapies, and CV risk, moderator (and recent Endo Society award winner) Dr. Daniel Einhorn implied that EMPA-REG OUTCOME and LEADER will inevitably be considered for the next iteration of the AACE/ACE diabetes treatment algorithm in some, as all guidelines must evolve to incorporate new data as they come out. Most importantly, the diabetes community needs to recognize the high incidence of heart failure, much of it previously unrecognized, and the need to treat it. Heart failure will be a major topic of research and teaching in the coming years. In a panel discussion, additional KOLs expressed their belief that the results of the EMPA-REG OUTCOME study are a class effect, though one hedged that he would not be “shocked” if subsequent SGLT-2 inhibitor CVOTs do not demonstrate a benefit due to differences in patient populations and trial designs. Mount Sinai’s very wise Dr. Zach Bloomgarden provided a compelling overview of the challenges of extrapolating data from diabetes cardiovascular outcome trials (CVOTs) to the general population of patients with diabetes. We agree heartily on that front.
4. At a Sanofi-sponsored educational symposium, moderator Dr. Guillermo Umpierrez (Emory University, Atlanta, GA), suggested that the FDA was overly conservative in indicating Xultophy and Soliqua only for patients who have previously failed to reach goal with a basal insulin or the component GLP-1 agonist, excluding those who have yet to intensify their first-line diabetes therapy. We totally agree with that too. The GLP-1 in these combos takes the edge off and for many patients, will be much better to start on than “pure” basal. Dr. Janet McGill (Washington University School of Medicine, St. Louis, MO) was very engaging in discussing the benefits of new basal insulin/GLP-1 agonist fixed-ratio combinations as diabetes therapy intensification options.
5. Dr. Richard Pratley (Florida Hospital Diabetes Institute, Orlando, FL) provided a fascinating overview of the management of comorbid diabetes and obesity, noting a recent “paradigm shift” such that obesity now frequently complicates the management of type 1 diabetes in addition to type 2 diabetes.
6. NIDDK’s legendary Dr. Judith Fradkin discussed progress toward the holy grail of precision medicine in diabetes, from insights already gleaned from clinical trials to ongoing and upcoming efforts from the NIDDK to better identify, characterize, and optimally treat subgroups of patients with diabetes.
7. In front of a packed plenary audience, Dr. William Tamborlane reminded us how far we’ve come from the “bad old days” of diabetes care, and how there’s more hope on the horizon. Notably he also shared some patients’ wish-list items for the MiniMed 670G.
8. Tulane University’s Dr. Vivian Fonseca outlined reasons for inertia in starting type 2 diabetes patients on basal insulin, and subsequently proposed strategies to overcome these barriers. Why is earlier intervention with insulin an important goal for diabetes care? Dr. Fonseca shared data to back up his claim that insulin therapy not only improves glycemic control, but empowers patients and enhances quality of life. We totally agree and are so happy to have seen inertia, often a white elephant, discussed so prominently at this meeting.
9. In an Amgen-sponsored but unbranded product theater, Louisville’s Dr. Harold Bays discussed modifiable vs. unmodifiable CV risk factors, arguing that there’s a lot more we could be doing to reduce modifiable risk factors, particularly diet/exercise and obesity. Boy is that fantastic to hear – it also raises the question about health citizenship – Margaret Anderson led a fascinating panel on this at the Milken Global Conference earlier this week. Dr. Bays listed “prior history of CV events” as an unmodifiable risk factor for future CV events, and, notably, suggested that we may soon be able to move this variable into the modifiable category with cardioprotective therapies like SGLT-2 inhibitors and GLP-1 agonists. To date, we think most patients think about drugs as a way to lower glucose, not as a way to avoid heart attacks, strokes, and dialysis – is this changeable?
10. In the exhibit hall on the tech side, we have notable updates from visits to J&J (OneTouch Via focused US launch in the coming months + WellDoc demo) and BD (no MiniMed Pro-set on display), as well as Abbott (lots of enthusiasm for FreeStyle Libre Pro and clamors for the consumer product, especially for type 2 patients and type 1s not interested in traditional CGM), Dexcom, Tandem, Valeritas, and Glooko.
Top 10 Highlights
1. Drs. Grunberger, Peters, & Wyne riff on CGM education, Outcomes Beyond A1c, and More
A 5 AM Dexcom-sponsored symposium featured countless pearls on CGM education and the psychology of reacting to trends, reimbursement, outcomes beyond A1c, and more from Drs. George Grunberger, Anne Peters, and Kathleen Wyne. Dr. Peters was happy about Medicare’s ruling to cover therapeutic CGM (just Dexcom G5 at this point), but reiterated what we have have been hearing from patients for weeks and Dexcom earlier this week – the devil is in the details. For example, local coverage determinations are still pending, meaning Dexcom’s 10,000+ interested Medicare patients are waiting to be shipped sensors; see our Dexcom 1Q17 report for more on this, including Liberty’s decision to stop processing for the time being. Dr. Peters told the audience (and Dexcom later confirmed in hallway chatter) that Medicare beneficiaries should directly contact Dexcom for now, and they will triage and help patients on a case-by-case basis. Some of the most valuable quotes (see below) touched on the psychology of wearing CGM, including non-adjunctive use and addressing feelings of failure. As always, we were also reminded of the insanity of reimbursement for CGM interpretation and the hoops these providers and patients must jump through. Earlier in the morning, Dr. Wyne offered practical tactics for helping patients get the most out of CGM: issues to consider when looking at CGM; insulin adjustment strategies (basal testing, post-meal monitoring); considering how yesterday affected today; and what questions to ask patients during a CGM review (What did you learn? What did you change, did it work? Did you consider looking at the evening prior to asses a morning glucose trend? What do you think we could work on changing for the future? These questions also reminded us of Margaret Anderson’s brilliant health citizenship panel at the Milken Global Conference - many patients’ mindset could be shifted quite dramatically). She also advocated for a CGM-first framework (giving a sensor to an MDI user at least one to four weeks before a pump), since (i) CGM-based glucose patterns can inform pump setup; and (ii) CGM has proven very effective in MDI. See the myriad quotable quotes from the symposium below.
- “I want everyone to get CGM-based education, whether or not I do it. There are people that I know won’t want to just take it out of the box and wear it – and there are educational materials, and YouTube, and neighbors, but I’d love to teach them some. I’m worried that some patients will overreact to data. I like using this time – a new tool, new teaching, a new approach – to help them benefit. The last thing you want is for failure to come into anyone’s brain. Tell patients that for the first two weeks we’re just getting a sense of who they are. Especially people running high, just be gentle because otherwise they’ll feel like a loser diabetic. I hate it when that happens.” – Dr. Peters
- “Reimbursement is one of the most frustrating aspects of our lives – imagine how much brain-power goes into what we do. Very few people appreciate the value we add. We’re stuck with ancient codes – one for insertion and one for interpretations – and no code (yet) for downloads. If patients get addicted to technology, you can help them, but you won’t get paid. Very frustrating. I have patients who will hold onto their Dexcom receiver in my office, won’t let my MA download, and I don’t get to see their data because their plan only covers interpretations twice per year. AACE is trying hard to make sure there are new codes to better reflect what we do in the 21st century. Not only wish us luck, but support us.” – Dr. Grunberger
- “It seems really stupid, taking CGM away from old, hypo-prone people who need it most. We won this battle. A few hiccups. A few things we have to document, but Liberty has ceased for the moment shipping out CGM for seniors – waiting to figure out the details of reimbursement. If a patient was on CGM and is older than 65, they need to contact Dexcom directly. We’re just in a transition period, figuring out payment -- it will be reimbursed, but they should contact Dexcom at the moment. I’ve been told it won’t be long, but there’s a huge demand. We need to make sure we don’t make wrong expectations at the moment.” – Dr. Peters
- “Imagine that someone in the 21st century is managing a patient on intensive insulin therapy not using CGM – it’s almost unconscionable.” – Dr. Grunberger
- “Therapeutic CGM requires new thinking –people have been dosing straight off a number for so many years. It does make sense, but how can you find the time in practice to describe it? It’s labor intensive. To teach people to think differently, it’s not really the number you’re treating. Can people add, subtract, divide? It requires practice, and if you don’t then it’s useless.” – Dr. Grunberger
- “We don’t have any studies showing the effect of CGM on depression and anxiety – that’d be a great study and should be run.” – Dr. Wyne
- “Unfortunately, the primary outcome of the GOLD trial was A1c, but anyone who takes care of patients with diabetes knows that A1c is not the key outcome.” – Dr. Grunberger
- “We’ve been so A1c-centric, and it’s not really our fault; regulators at FDA said if you want to get to the market for diabetes, you have to lower A1c. … But with tech, based on glucose management, some patients will be obsessed with having an A1c of 5.1%, but for most, A1c is not the key metric. FDA had a public workshop in August about going beyond a1c. We were very vocal about things like time in range, hypoglycemia, and quality of life measures. A little soft, but gaining currency.” – Dr. Grunberger
- “A disadvantage of CGM is that, since you can see data all the time, you may want to keep bolusing. It’s good at end of the day if they can see hypoglycemia because it allows me to walk it back and show them how not to stack insulin.” – Dr. Grunberger
- “I finally talked a 22-year-old male into wearing CGM. He was in tears – he had been told for years that he’d been doing great, and didn’t expect the results he got. He had no idea that he was going low most nights and going high after meals. He’s worked hard to change variability, and needs to take insulin before meals.” – Dr. Wyne
- “My brain likes simplicity. The beauty of Tidepool is I have it on my dashboard. I don’t even have to plug in my password, I can just go through five different patients’ traces very quickly. Even 30 seconds of additional work drives me crazy. I, like many of you, look at data in my free time at night, which is free, volunteer work.” – Dr. Peters
2. DreaMed’s Advisor Pro Clinical Decision Support System Pivotal Study to Begin Late this Summer
In an aptly-titled “Meet the Experts” session, DreaMed’s Dr. Moshe Phillip shared that the clinician-facing Advisor Pro decision support system will enter a pivotal study “toward the end of July/early August.” The trial will be supported by the Helmsley Charitable Trust. The clinical decision support software will be integrated with Glooko’s platform, allowing clinicians to get advice on therapeutic adjustments for patients using CGM and pumps, though SMBG and MDI are also in development. Further, Dr. Phillip expressed that the software will be limited to provider-facing use at first, but once it gains their trust, he sees no reason why it can’t be tailored for patients at some point. In initial data relating to the Advisor shown at ATTD, the hypothesis of non-inferiority to real physicians has been validated: For six weeks, patients at Schneider Hospital assigned to either the Advisor (n=7) or the control group (expert physician-guided decisions; n=8) have spent similar time in range (52% in control vs. 50% with the Advisor), though the Advisor group spent slightly more time in hyperglycemia >180 mg/dl (42% control vs. 49% Advisor), and much less time in hypoglycemia <70 mg/dl (7% control vs. 2% Advisor). We are very excited about this software and others like it – the scalability and mathematically-driven titration are very exciting and should hopefully save providers a lot of time, while improving patient outcomes. The bigger key will be the go-to-market approach and design of these systems: What’s the business model (who pays and how much)? How much burden will these systems be to prescribe and use? How much confirmation will providers need to give for updated doses vs. letting systems run on their own and give recommendations straight to patients (once pre-configured)? Dr. Phillip also offered his thoughts on a litany of topics, ranging from the benefit of factory calibration, to Fiasp, and beyond – see below.
- “With Libre, which is factory calibrated, people don’t doubt the reading, because they’re not checking SMBG and seeing that the sensor is 10 mg/dl off. It’s like Waze [a navigation app] – it gets you to work in 40 min and you think it’s good, the best possible route but you have no control group. If you did, perhaps you’d trust Waze a little less.” That isn't to say that patients don't trust factory-calibrated sensors, but exactly the opposite; even though +/- 10 mg/dl is actually very accurate, consistently seeing different numbers on two separate devices could wear away at someone’s trust in the sensor.
- “We’re currently running a study of Fiasp in pediatrics and adults. I’m afraid to share results because it’s confidential, but tailor your expectations to reality. It’s better, but not really immediate action.” This seems to be the consensus, both anecdotally and clinically: Phase 3 data have led some to suggest that Fiasp does not represent quite as significant of a leap forward as next-generation basal insulins, though we know many patients could still stand to benefit from Fiasp’s potential for tighter postprandial control, less hypoglycemia, and perhaps more flexible dosing. On the other hand, we have seen patients on social media exclaiming that Fiasp is a gamechanger. Hmmm ... the notion from our view that incremental benefit should be criticized is anathema to thinking about benefit overall.
- “As diabetologists, we are like advisors in a bank – we tell patients how to invest, but eventually they go home and treat themselves. All we do is diabetes psychology.” We thought this was a brilliant point, since it really underscores the value of technology and the changing role of HCPs – as algorithms analyze more data and give recommendation, HCPs should have more time to actually talk to patients.
- “I gave the same lecture a few days ago in Greece, and very few people could download data in their clinics, and very few type 2s had pumps. It’s obviously different here. I like this country.”
3. Positive CVOTs: Generalizability, Class Effect, First-Line Therapy?
In an AZ-sponsored corporate symposium on the connection between diabetes, diabetes therapies, and CV risk, moderator Dr. Daniel Einhorn implied that EMPA-REG OUTCOME and LEADER have been incorporated into the next iteration of the AACE/ACE diabetes treatment algorithm in some fashion. He shared that the AACE/ACE guidelines writing committee had met that very afternoon and one of the chief questions on the agenda was what kind of recommendation these groundbreaking trials could support for empagliflozin and liraglutide, respectively. In particular, when asked in Q&A if empagliflozin and/or liraglutide could be positioned as first-line therapy (at least in those with cardiovascular disease), either replacing or alongside metformin, Dr. Einhorn responded, “That’s exactly the question AACE grappled with.” He emphasized that guidelines must follow clinical evidence as best as possible and strive to present the material in a coherent, easy-to-understand algorithm graphic. He teased, “I can’t tell you what we came up with, but you’ll see it soon and I think we resolved it in an elegant way.” As a reminder, the recently-updated ADA Standards of Care recommend empagliflozin and/or liraglutide in the treatment of patients with type 2 diabetes and existing cardiovascular disease, but does not go so far as to position these agents as first-line therapies. It would be a paradigm shift indeed to dethrone metformin as THE first-line therapy, though the AACE/ACE algorithm has historically been somewhat less conservative than the ADA/EASD guidelines so it’s fitting that they may be the first set of guidelines to take this monumental step.
- In a panel discussion, both Drs. Lawrence Blonde and Mikhail Kosiborod expressed their belief that EMPA-REG OUTCOME is a class effect. The question of whether the impressive cardioprotective (and renal) benefits demonstrated for Lilly/BI’s Jardiance in EMPA-REG OUTCOME apply to other SGLT-2 inhibitors has set the field abuzz in the last 1.5 years since the results were presented at EASD 2015 – and we’ve all been waiting with bated breath for results from the second SGLT-2 inhibitor CVOT to (hopefully) confirm the results. The CANVAS trial for J&J’s Invokana will report in just over a month at ADA 2017, but the conspicuous silence on topline results from J&J management has us wary that the results may not replicate the large benefit seen in EMPA-REG OUTCOME. Oveall, however, it’s too early to tell. Indeed, Dr. Blonde suggested that it was possible that subsequent SGLT-2 inhibitor CVOTs may not demonstrate all of the same positive results due to differences in patient populations and trial design. We also heard a similar hint that CANVAS may not be a positive as hoped for from Dr. David Nathan at ENDO 2017… whatever the outcome, we shall learn it soon. Overall though, Dr. Blonde clearly feels that if subsequent SGLT-2 inhibitor CVOTs did not demonstrate all of the same positive results seen in the EMPA-REG trial, it would not necessarily indicate that there is not a “real” class effect. Similarly, Dr. Kosiborod suggested that the determination of class effect will come from two key kinds of evidence: (i) additional CVOTS and (ii) largescale, real-world observational studies like CVD-REAL. Presented the ACC 2017, the study found that patients taking any SGLT-2 inhibitor experienced risk reductions for CV events comparable to the risk reductions observed in EMPA-REG OUTCOME, despite the fact that the vast majority of participants were taking Invokana or Farxiga rather than Jardiance. Furthermore, these risk reductions remained significant regardless of type of SGLT-2 inhibitor, leading Dr. Kosiborod to suggest that the data thus far all points to a class effect.
- Mount Sinai’s highly regarded Dr. Zach Bloomgarden provided a compelling overview of the challenges of extrapolating data from diabetes cardiovascular outcome trials (CVOTs) to the general population of patients with diabetes. Overall, he suggested that the design and participant inclusion/exclusion criteria for modern CVOTs limits their applicability to the “average” type 2 diabetes patient in clinic. In terms of design, he argued that “practical” durations for trials (on the order of years) may not be sufficient to tease out a cardioprotective benefit (which can take decades to manifest). As he put it, “We’re dealing with a disease that lasts decades and we want to base our clinical recommendations on relatively short trials that may not be applicable.” In addition to the length of the trial, the enrollment criteria can exclude a substantial proportion of the general population with type 2 diabetes. Dr. Bloomgarden pointed to a 2013 literature review that applied the enrollment criteria of five largescale outcomes studies (ACCORD, ADVANCE, PROactive, RECORD, and VADT) to members of a Scottish diabetes registry and found that, at most, only about a third of participants in the registry would have been eligible for enrollment (36% eligible by ADVANCE enrollment criteria, compared to 18% by VADT criteria, 11% by ACCORD criteria, 9% by RECORD criteria, and just 4% by PROactive criteria). Beyond the enrollment parameters included in the trial design, Dr. Bloomgarden also pointed out that participation in a clinical trial is self-selecting and thus these volunteers may not represent the general population either. In our view, these very valid concerns further underscore the need for long-term, real-world studies to complement randomized clinical trial data to help answer some of these questions. Dr. Bloomgarden acknowledged that innovative trial designs that retain randomization while addressing these issues would be extremely helpful, but he suggested that the exact design of such trials and how they would work is not clear at this point. In lieu of disruptive randomized trial design, Dr. Bloomgarden suggested that epidemiological observational data may shed some light on the generalizability of clinical trial results.
4. Basal Insulin/GLP-1 Agonist Combination Indication Too Conservative, Given Clinical Benefits
At a Sanofi-sponsored educational symposium, moderator Dr. Guillermo Umpierrez (Emory University, Atlanta, GA), suggested that the FDA was overly conservative in indicating Xultophy and Soliqua only for patients who have previously failed to reach goal with a basal insulin or the component GLP-1 agonist, excluding those who have yet to intensify their first-line diabetes therapy. Indeed, this was a major discussion point at the FDA Advisory Committee Hearings for both Xultophy and Soliqua, and we certainly agree that these combinations, which boast both a reduced side effect profile and enhanced clinical efficacy compared to either component monotherapy, are in many ways an ideal choice for insulin-naïve patients who are not at goal. Further, as a GLP-1 agonist intensification option, both products are currently only indicated for insulin-naïve patients who are already on the component GLP-1 agonist, excluding patients who may be on, say, Trulicity. This is especially a disadvantage for Soliqua, as very, very few patients are on standalone lixisenatide (hence the laser-focus on positioning Soliqua as a basal intensification option, we assume). Dr. Vivian Fonseca noted that the FDA could indicate these combinations for a wider patient population in the future, but not without more data. He pointed out that although the benefit of initiating injectable therapy with combinations over basal insulin or a GLP-1 agonist alone is obvious to clinicians, as a regulatory body the FDA must take a slower and more conservative stance, although it is being perhaps “overly cautious” in this case. To this end, past AACE president Dr. Yehuda Handelsman (Metabolic Institute of America, Tarzana, CA) provocatively argued that Novo Nordisk and Sanofi “didn’t do their job” at their respective Advisory Committee meetings for Xultophy and Soliqua in failing to secure an indication for a wider patient population. All we can hope is that with more time and more familiarity the convenience, patient friendliness, and high efficacy of these newly-launched combinations becomes more widely appreciated, and that these drugs will become accessible – both in terms of cost and in terms of label indication – for a wider array of people who could greatly benefit from them.
- Dr. Janet McGill (Washington University School of Medicine, St. Louis, MO) discussed the benefits of new basal insulin/GLP-1 agonist fixed-ratio combinations as a diabetes therapy intensification option. So great are the clinical benefits of these combinations that Dr. McGill framed them as a distinct milestone in the now 95-year history of insulin therapy development, comparable to the improvement that came from long-acting analogs over human insulin – wow! She took a deep dive into the impressive clinical data for Novo Nordisk’s Xultophy (insulin degludec/liraglutide) and Sanofi’s Soliqua (insulin glargine/lixisenatide), noting common themes of reduced weight gain (even weight loss), reduced hypoglycemia, and improved A1c, FPG, and PPG for combinations over each of their component monotherapies. Dr. McGill convincingly pointed out that the major limitations to reaching glycemic goals with insulin therapy are hypoglycemia, weight gain, and the complexity of an insulin regimen for the patient, so combinations like Xultophy and Soliqua – with their reduced side effect profile and greater ease of use – are in many ways an ideal alternative, not to mention their improved A1c efficacy over traditional insulin or GLP-1 agonist therapy alone.
5. Obesity Management in Type 1 Diabetes: An “Evidence-Free Zone”
Dr. Richard Pratley (Florida Hospital Diabetes Institute, Orlando, FL) provided a fascinating overview of the management of comorbid diabetes and obesity, noting a recent “paradigm shift” such that obesity now frequently complicates the management of type 1 diabetes in addition to type 2 diabetes. As a testament to the importance of obesity management in diabetes care, this session was standing room only. Despite an increasing body of evidence surrounding the pharmacological and surgical management of obesity in people with type 2 diabetes, Dr. Pratley characterized the landscape of obesity management in type 1 diabetes as an “evidence-free zone.” On the pharmacotherapy front, virtually no studies exist investigating the efficacy of obesity medications in people with type 1 diabetes. However, some limited data exists on the efficacy of various type 2 diabetes medications with weight loss effects (namely GLP-1 agonists and SGLT-2 inhibitors) in people with type 1 diabetes and obesity. Novo Nordisk’s Victoza (liraglutide) is perhaps the most investigated therapy option for weight loss in type 1 diabetes: in the Lira-1 trial and the ADJUNCT ONE and ADJUNCT TWO trials, patients experienced modest ~4-5 kg (8.8-11 lbs) weight loss and ~0.2% A1c reduction with Victoza added to insulin therapy. Novo Nordisk declined to pursue an expanded indication for Victoza in type 1 diabetes after these underwhelming results due in part to worrisome safety signals for DKA and hypoglycemia. On a different note, safety and efficacy studies for the SGLT-2 inhibitor empagliflozin (Lilly/BI’s Jardiance) and SGLT-1/2 dual inhibitor sotagliflozin (Sanofi/Lexicon’s phase 3 candidate) in type 1 diabetes have shown modest weight loss benefits, though the high-profile DKA controversy associated with this class has some wary (we continue to believe that the risk can be managed through concerted patient and provider education efforts). A similar lack of evidence exists for bariatric surgery in type 1 diabetes, though a case review meta-analysis encompassing 107 patients with type 1 diabetes and obesity concluded that surgery, in addition to decreasing BMI, can decrease patients’ insulin requirements and modestly lower A1c, though at the risk of increased ketoacidosis. This is an area in which we’d love to see more work. As the obesity epidemic persists, the proportion of people with comorbid obesity and type 1 diabetes will only rise and we look forward to a future where clinicians better understand how to help patients manage the two synergistically.
6. NIDDK’s Dr. Judith Fradkin on the Potential and Progress of Precision Medicine in Diabetes
NIDDK’s legendary Dr. Judith Fradkin discussed progress toward the holy grail of precision medicine in diabetes, from insights already gleaned from clinical trials to ongoing and upcoming efforts from the NIDDK to better identify, characterize, and optimally treat subgroups of patients with diabetes. Several NIDDK-sponsored trials are ongoing that will hopefully not only shed more light on different kinds of diabetes therapies, but also on the kinds of patients that might benefit most from these therapies. The GRADE comparative effectiveness study hopes to both comparatively assess the efficacy and safety of a sulfonylurea, a DPP-4 inhibitor, a GLP-1 agonist, and insulin (SGLT-2 inhibitors were not yet approved when this study was conceived – the lack of SGLT-2 inhibitor arm is truly unfortunate and a major shortcoming of this trial and its eventual results in our view). Further, the study seeks to determine the patient characteristics that might be associated with different responses to these drugs and the molecular pathways that might be involved in this differential response – to that end, the study is collecting genetic samples and stool samples (for microbiome screening) from participants. Dr. Fradkin also hopes that the long-term DPP Outcome Study (DPPOS) will be able to help predict which patient populations may benefit from long-term metformin therapy from an outcomes perspective. The trial is an extension of the DPP trial, in which participants with prediabetes originally randomized to metformin continued therapy while those not originally taking metformin only began the medication if prescribed by their doctor following development of type 2 diabetes. As such, Dr. Fradkin highlighted that this trial offers the largest randomized exposure to metformin ever. The trial hopes to assess the impact of metformin on cardiovascular disease, cancer, cognitive function, quality of life, and cost. Dr. Fradkin suggested that it will be especially useful to determine which subgroups are likely to benefit from metformin’s impact on cardiovascular disease and cancer.
- Overall, Dr. Fradkin highlighted two main strategies through which NIDDK hopes to advance precision medicine: (i) the examination of rare and extreme diabetes phenotypes to gain insight into pathology; and (ii) the application of “omics” approaches in clinical studies. She emphasized that NIDDK is very interested in partnering with AACE on the first approach, as AACE member endocrinologists are more likely to come across unique and complex diabetes cases that can provide valuable information. Additionally, if the NIDDK is alerted to this difficult cases, it can help the physician characterize the patient and determine the best course of treatment as well – a win-win situation. On the omics front, Dr. Fradkin highlighted the Accelerating Medicines Partnership, an NIH/industry collaboration to create an open-access portal of genetic and clinical data from over 100,000 patients with type 2 diabetes. The portal is available for anyone to analyze its data and could be used to identify novel therapeutic targets for type 2 diabetes.
- While in some ways, “precision medicine” on the level regularly practiced in oncology seems a thing of the future for diabetes and prediabetes, Dr. Fradkin pointed out that we’ve already learned valuable information from large, long-term trials of diabetes prevention. For instance, in the landmark Diabetes Prevention Program, in the overall cohort, intensive lifestyle therapy was found to be the most effective diabetes preventive intervention, followed by metformin, and then placebo. However, a subgroup analysis revealed that metformin was especially effective as a preventive therapy in younger patients (aged 25-44) – in fact, in this age group, metformin was about as effective as lifestyle therapy. On the other hand, metformin was much less effective as a prevention (nearly placebo rates of “efficacy”) in those aged 60 and older, while lifestyle in this group was even more effective than in the youngest age group. Similarly, in DPP, metformin was much more effective in women with a history of gestational diabetes than those without. Another trial, the TODAY study of children with type 2 diabetes, found that black participants specifically benefited from the addition of rosiglitazone or lifestyle therapy to metformin. Also Dr. Fradkin pointed to data from that study population as a whole showing that A1c achieved after treatment with metformin during the run in prior to randomization correlated strongly with subsequent loss of glycemic control. This information suggests that more aggressive treatment may be required when youth with T2D fail to achieve near normalization of A1c in response to metformin.
- In diabetic retinopathy, too, Dr. Fradkin explored how existing data can help individualize treatment decisions for this complication. Three VEGF inhibitors are currently commonly used to treat retinopathy: Roche/Novartis’ Lucentis (ranibizumab), Genetech’s Avastin (bevacizumab), and Bayer/Regeneron’s Eylea (aflibercept). In a comparative study of all three agents, Eylea was found to be substantially more effective at restoring visual acuity in patients with baseline acuity of 20/50 or worse. On the other hand, all three agents were comparably effective in patients with acuity better than 20/50. Dr. Fradkin pointed out that, importantly, Avastin is now generic and thus much more inexpensive than the other two agents. As a result, Dr. Fradkin suggested that these findings lend themselves to the recommendation for costly Eylea therapy in patients with visual acuity of 20/50 or worse and cheaper Avastin therapy for patients with better vision.
7. Dr. William Tamborlane: We’ve Come a Long Way from the Bad Old Days of Diabetes management
In front of a packed plenary audience, Dr. William Tamborlane reminded us how far we’ve come from the “bad old days” of diabetes care, and how there’s more hope to be had on the horizon. To Dr. Tamborlane, any day pre-1980 is considered the “bad old days” – patients were limited to beef and pork insulin, then regular insulin, all of which was often impure. There was no good way to monitor blood glucose – he recalled how physicians at Yale used to “torture youngsters” by asking them to test their urine glucose, and clinic visits were predicated on a single fasting glucose measurement (“that really helped a lot…not”). Aggressive therapy was unsafe and had unknown benefits, the typical adolescent A1c was between 11% and 12%, and it was common for young adults to develop microvascular complications. For Dr. Tamborlane, the “era of intensive treatment” began in the 1980s. He reminisced back to the Reflectance meter, one of the first dinosaurs of a glucose monitor: “Those of us who were around for it, we get a kick out of all the kvetching over the accuracy of CGM. It was this or nothing, so accuracy didn’t matter. The difference of blood glucose could be 150 mg/dl on the Clark Error Grid and it’d still be ok.” In 1979, a strapping young Dr. Tamborlane was first author on NEJM publication demonstrating for the first time that CSII can be used to treat patients with type 1 diabetes. Throughout this whole portion of the talk, we couldn’t help but recall the quote (usually attributed to Bill Gates) about how we overestimate the change that will occur in two years and underestimate the change that will happen in ten years. We really have come a long way, with treatment advances such as insulin analogs, smart insulin pumps, improved BGM accuracy, and CGM, yet the Inconvenient Truth is that the majority of people with diabetes are still not at their target A1c – the average A1c of adolescents in the DCCT was 9.5%, and according to 2015 T1D Exchange data, it is still over 9%. Dr. Tamborlane sees light at the end of the tunnel in the form of closed loop systems, new adjunctive therapies for type 1, and biologic solutions (transplant, stem cell therapy), but his group knows better than most that current options aren’t perfect. On the MiniMed 670G in particular, he said that patients would love to be able to: (i) adjust target glucose levels; (ii) manually set temp basals; (iii) manually give correction doses that correct to glucose levels <150 mg/dl; and (iv) track glucose and insulin delivery remotely on smartphone apps. Considering the magnitude of progress since the DCCT, we can’t wait to see what diabetes management looks like in another 25 years.
8. Overcoming Barriers to Initiating Insulin in Type 2 Diabetes
Tulane University’s Dr. Vivian Fonseca outlined reasons for and strategies to address clinical inertia in basal insulin initiation in type 2 diabetes patients. As Dr. Fonseca put it, insulin is tricky drug, one that requires complicated dosing and titration. Providers worry about patients missing dosing or not being able to titrate properly, and they shy away from prescribing a therapy that may cause hypoglycemia or induce weight gain. Fear of hypoglycemia and a desire to avoid weight gain affect patient perceptions of insulin therapy as well, and surveys show that between 17% and 28% of type 2 patients are unwilling to try a basal insulin product. Additionally, Dr. Fonseca pointed out that all-too-often, providers use insulin as a threat for their patients with type 2 diabetes, and the natural patient response is to view initiation of basal insulin as a failure on their part. Above all, there’s also the issue that busy healthcare providers don’t feel they have the time to thoroughly educate patients on insulin titration for optimal outcomes. Dr. Fonseca positioned education as step no. 1 in overcoming this clinical inertia, and he expressed some optimism that it will become more feasible as we move away from fee-for-service toward value-based healthcare. Currently, there’s no good system in place to reimburse providers for extra time spent on education, but given how critical this educational support can be for patient outcomes, it will naturally become more central in a value-based model – boy would we love to see this change! Dr. Fonseca also encouraged more reliance on diabetes educators and a broader diabetes care team to supply patient education alongside insulin therapy. He highlighted group-based education as another time-saving possibility. Dr. Fonseca emphasized that starting insulin should be a shared decision between patient and provider, and that HCPs should create an insulin regimen that fits into a patient’s everyday life. All of this rung incredibly true to us, and we appreciated Dr. Fonseca’s clear tips and tricks to beat inertia.
- Dr. Fonseca proposed practical solutions for other barriers to initiation as well:
- Patients sometimes forget insulin doses, which reduces the drug’s A1c-lowering efficacy, but we can now offer alerts, alarms, or reminders with fairly simple technology.
- Some patients list injection pain as an obstacle, but this is becoming less of a problem with newer insulin pens and pumps.
- Combining insulin with an SGLT-2 inhibitor can address concerns of weight gain (since SGLT-2 inhibitors have been associated with weight loss).
- Providers shouldn’t be positioning insulin as a last resort or sign of treatment failure, and should consider CGM for their type 2 diabetes patients who are particularly prone to or afraid of hypoglycemia (or, individuals with hypoglycemia unawareness).
- Dr. Fonseca also established, early on in his talk, why earlier intervention with insulin is beneficial in diabetes care. Data shows that insulin therapy not only improves glycemic control, but empowers patients and enhances quality of life. As we push for greater consideration of outcomes beyond A1c, we’re particularly excited to see data linking insulin to time in zone and quality of life metrics. While he said the diabetes community is not yet sure why insulin improves patient quality of life, Dr. Fonseca suggested a few possible explanations – tighter glycemic control, a greater sense of self-efficacy, or sharpened cognitive function (also associated with blood glucose-lowering).
9. How to Modifiy the Modifiable Risk Factors in CV Prevention
Louisville’s Dr. Harold Bays discussed modifiable vs. unmodifiable CV risk factors, arguing that there’s a lot more we could be doing to reduce modifiable risk factors, particularly diet/exercise and obesity. While there’s little medicine can do to affect unmodifiable variables like age and race, Dr. Bays urged providers in the room to capitalize on opportunities to implement lifestyle interventions. That said, he acknowledged a glaring limitation to nutrition and exercise research: “We don’t do a very good job – as scientists, as clinicians, as researchers – sending clear messages on what is healthy vs. unhealthy diet and exercise.” The first step, then, is establishing clinically-grounded and easy-to-follow algorithms for dietary interventions and physical activity regimens. Suitable and standard guidelines for diet and exercise are still lacking in medicine. Dr. Bays shared his opinion that the “best” diet or exercise regimen are whichever ones a patient can stick to, as this promotes self-efficacy and health engagement. Even if the “best” a patient can commit to is light walking, Dr. Bays underscored that a small increase in exercise can still influence CV risk. He presented obesity as another modifiable risk factor for CV events, and made a compelling point on how to tackle stigma: The practice of obesity management needs to borrow language from the diabetes field, and providers should refer to “patients with overweight or obesity” rather than “obese patients,” just as endocrinologists have reached a consensus more or less on addressing “patients with diabetes” rather than “diabetics.” Dr. Bays explained how this choice vocabulary reflects a priority to treat the whole person, not just their disease. We couldn’t agree more on the value of terminology, and we see profound effects of vocabulary in the practice of treating obesity, where stigma abounds and where providers show an unconscious bias against people with overweight or obesity. An important first step to improve chronic weight management is promoting the concept of obesity as a chronic, biological disease, and vocabulary could go a long way in counteracting stigma and correcting biases.
- Dr. Bays listed “prior history of CV events” as an unmodifiable risk factor for future CV events but suggested that we may soon be able to move this variable into the modifiable category. Advanced therapies for diabetes, including Novo Nordisk’s GLP-1 agonist Victoza (liraglutide) and Lilly/BI’s SGLT-2 inhibitor Jardiance (empagliflozin), have shown CV benefit in long-term outcomes studies – the LEADER and EMPA-REG OUTCOME trials, respectively, demonstrated how these agents significantly reduce CV risk in people with a prior history of CV disease. It’s tremendously exciting that diabetes providers are now able to prescribe medicine to modify this risk factor though we think it’s very early days – we’re certainly eager to see “prior history of CV events” transitioned into a category of modifiable variables in CV prevention.
10. Exhibit Hall
Our team explored the modestly-sized AACE exhibit hall today – below we include a look at 16 of the booths. On the tech side, we have notable updates from visits to J&J (OneTouch Via focused US launch in the coming months + WellDoc demo) and BD (no MiniMed Pro-set on display), as well as Abbott (lots of enthusiasm for FreeStyle Libre Pro), Dexcom, Tandem, Valeritas, and Glooko. Among therapy companies, Amgen, AstraZeneca, Janssen, Lilly, MannKind, Merck, Novo Nordisk, and Sanofi were represented.
Detailed Discussion and Commentary
The Abbott booth was essentially identical to that at ENDO 2017 – entirely dedicated to the FreeStyle Libre Pro (retrospective, blinded) professional CGM, with a tiny sliver calling attention to AGP with the tagline “the more you see, the more you can do.” The product launched in the US last fall, meaning this was the second time Libre Pro was not under glass in the US. The only difference we spotted since a month ago is that more providers have experience of how Libre Pro convinced someone to change behavior or picked up previously unidentified nighttime hypoglycemia – HCPs love it here, and some have even said they don’t know how they got along without it. We asked reps how the real-time consumer Libre FDA review is going, to which they responded that they’re not sure, but they are excited to sell it. One told us that whenever his team asks him about timing, he responds with the same five words CEO Miles White used on the 1Q17 quarterly earnings call: “Submitted. Waiting. Excited. Anticipating. Impatient.” The consumer version was submitted to FDA for both an adjunctive claim and a non-adjunctive (replacement) claim back in 3Q16, and management last guided for a 2H17 approval – we last heard that on the 4Q16 call, but of course FDA is very hard to predict.
Amgen occupied a mid-sized booth decked out in the company’s classic royal blue and white color scheme at the front of the exhibit hall. The booth was almost entirely dedicated to the company’s PCSK9 inhibitor Repatha (evolocumab), featuring touchscreen displays animating the drug’s mechanism of action and large wall displays highlighting the drug’s efficacy data and ability to “maximize LDL reduction in one move.” A particularly prominent sign on a pedestal in the middle of the booth read “91% of adults covered” – a response, we imagine, to widespread concerns over affordability and accessibility of the PCSK9 inhibitor class. There were no hints of Repatha’s recently-demonstrated risk reduction for cardiovascular death – certainly a differentiating factor for the drug – likely due to the fact that the FOURIER CVOT reported only just over one month ago, and this data is not yet included on the label for Repatha (meaning Amgen is not allowed to discuss the data in its promotional materials).
AstraZeneca’s AACE 2017 presence featured a smaller, pared-down booth compared to what we’ve seen in past exhibit halls. Rather than highlight the full range of AZ diabetes products, the booth only featured signage and information for three therapies: SGLT-2 inhibitor Farxiga (dapagliflozin), combination Xigduo (dapagliflozin/metformin), and GLP-1 agonist Bydureon (exenatide once-weekly). We’re not surprised AZ is especially emphasizing these products, especially after its 1Q17 update in which management made clear that Farxiga especially is a cornerstone of the company’s growth strategy for its newly-formed Cardiovascular and Metabolic Disease unit. AZ is also undoubtedly looking ahead to CV outcomes for Farxiga and Bydureon – indeed, AZ representatives at the booth shared with us that many attendees were asking about the CVOTs for Farxiga (DECLARE) and Bydureon (EXSCEL). As we wait for results, AZ representatives highlighted the non-glucose-lowering benefits of Farxiga, especially the weight loss and blood pressure reductions observed in trials. Not even the logos for DPP-4 inhibitor Onglyza (saxagliptin), combination Kombiglyze (saxagliptin/metformin), or first-generation GLP-1 agonist Byetta (exenatide twice-daily) could be found anywhere on the AZ booth – a departure from the usual style. We were particularly disappointed by the lack of any sort of combination Qtern (saxagliptin/dapagliflozin) promotion as well – the product was approved in the US in March 2017 and we’ve been looking to AZ to grow the SGLT-2 inhibitor/DPP-4 inhibitor combination class. We think the combined efficacy profile of these combinations are particularly promising and we’ve been disappointed with their sluggish sales since the launch of Lilly’s Glyxambi (empagliflozin/linagliptin) in 2015.
The BD booth didn’t showcase the MiniMed Pro infusion set with FlowSmart technology, a reminder that the set is on hold right now – good news from our view that it was tested and the companies are learning. Reps indicated that BD and Medtronic are working on optimizing the training protocol together (beginning a trial to validate updated training), and will probably perform another limited launch before opening it up to the broad market. We’re very glad to see careful rollout to ensure an optimal experience and while some may say it’s taking too long, we think they are exactly right to take the time needed. While shipments were temporarily halted following an initial limited launch (~500 customers) due to higher than expected number of reported complaints related to kinked cannulas and elevated blood glucose levels, management and patients frequently maintain that feedback has been positive overall. One NP AACE attendee claimed that the Pro set was the most comfortable set he’d ever worn – he exclusively inserted manually without incident (kinking, occlusion), and he can’t wait until it’s back on the market. We expect the re-launch will focus more on the inserter device since this seems a key to success.
The Dexcom booth was similar to that seen at ENDO, with materials related to the web-based Clarity data platform, the efficacy of CGM in MDI, and Medicare reimbursement. On the 1Q17 call earlier this week, we learned that 10,000+ Medicare patients are awaiting G5 shipment, as final local coverage determinations have not been established (hopefully expected in 2Q17). Dexcom told us that Medicare beneficiaries looking for CGM should get in touch with the company, and they will triage and handle each individual on a case-by-case basis. Dexcom said that the few claims it has submitted have been “pretty much” denied across the board, so we think things are pretty much at a standstill until the coverage decisions come through.
A Glooko data scientist was present in the company’s booth in order to recruit providers for a study to optimize the “Best Day” pattern recognition feature of the platform – “who’s to say what the best day is?” He was looking to attract >30 clinicians to complete a survey that would get at what they consider to be a “good day” – more time in range? Minimal time in hypoglycemia? Hyperglycemia? (We vote all of the above, but with a focus on time-in-range and minimal variability.) He could then measure the agreement between physicians and compare the modal response to the algorithm, and eventually adjust the algorithm to reflect the values of the providers. This is a neat idea that could help patients figure out the behavioral and treatment decisions that lead to the best day-in day-out diabetes experience, and we wonder how patients and physicians might have different views. (We suspect patients care more about time-in-range, while physicians might talk more about average/A1c with hypoglycemia.)
J&J – Janssen
Half of J&J’s rather spacious booth was dedicated to the SGLT-2 inhibitor Invokana (canagliflozin) franchise, while half was devoted to LifeScan/Animas (see below). Invokamet XR (canagliflozin/metformin extended-release), FDA-approved last September, was highlighted front-and-center – an eye-catching overhead sign emphasized in red text that the combination product comes with once-daily dosing. Indeed, the added convenience of a single tablet rather than having to schedule two daily doses is a major selling point for Invokamet XR over its predecessor, Invokamet. From a commercial standpoint, it makes sense that J&J is most-heavily promoting the newest combination product within its SGLT-2 inhibitor business to spark additional uptake. Tall posters throughout the exhibit also displayed safety/efficacy data on standalone Invokana, with one banner announcing >11 million prescriptions written to-date. Despite plummeting sales in 1Q17, Invokana continues to lead the SGLT-2 inhibitor class in sales, while AZ’s Farxiga (dapagliflozin) leads the class in prescription volume.
J&J – LifeScan/Animas
On the OneTouch side, the bolus-only patch delivery device, OneTouch Via (formerly Calibra Finesse), is expected to roll out in a focused US launch in the coming months, beginning on the east coast and migrating west. We were glad to see WellDoc represented at the LifeScan booth, marketing the BlueStar/OneTouch Verio Flex BGM integration allowing passive blood glucose data integration in to the type 2 diabetes management software – nice! The WellDoc rep took us through a lengthy demo of the app, including the recently-added BlueStarU – a function of the AADE partnership. The beautifully-designed educational module consists of 91 lessons in 21 courses in eight topics – the rep said a patient could complete all of the lessons in about 12 weeks, minimum. WellDoc also has a partnership with Human API in the works to passively upload lab values (e.g., lipids, A1c) into the app. Animas showed the Vibe and Ping pumps, though didn’t have a timing update for the OneTouch Vibe Plus pump with Dexcom G5 integration. We were glad to see that J&J, in the midst of “seeking strategic options” for LifeScan/Animas/Calibra, was present in the hall.
Lilly’s AACE 2017 booth was nearly a carbon-copy of its ENDO 2017 presence, right down to the delicious, high-traffic espresso bar centered in front of the enormous Lilly logo. Flanking each side of the espresso station were standalone panels each highlighting a major product in Lilly’s robust diabetes portfolio: on one side, SGLT-2 inhibitor Jardiance (empagliflozin), DPP-4 inhibitor Tradjenta (linagliptin), combination Glyxambi (empagliflozin/linagliptin), and Basaglar (biosimilar insulin glargine); and on the other side, GLP-1 agonist Trulicity (dulaglutide), the Humulin U500 KwikPen, and the Humalog U200 KwikPen. Additionally, in a prominent space between the insulins and the coffee, Lilly’s booth-within-a-booth on patient affordability and access made a return. We’ve been impressed by the dual-pronged, concrete steps the company is taking to address rising out-of-pocket costs for insulin and relieve financial burden at the patient level. First, Lilly launched a direct-to-patient discount insulin program in partnership with Blink Health this January. Taking it one step further, we recently learned that Lilly has begun engaging payers and employers directly to consider including insulin as a separate, copay-free benefit category within their health plans – we’re especially impressed by this effort to try and effect systems-level change on behalf of patients. The Lilly representative manning this section of the booth at AACE shared that these conversations continue, though no concrete progress has yet been made with any plans signing on to take this novel step.
MannKind occupied a small but colorful booth on the edge of the AACE exhibit hall. The backdrop featured a playful message – INsulin, 12-15 minutes; OUTsulin, three hours – and sales reps positioned inhaled insulin Afrezza as an ideal option for bolusing because it’s quick in, quick out. Reps described the high incidence of hypoglycemia that stems from prandial insulins with slower offset, which is a story we hear all too often. This emphasis matches MannKind’s overarching commercial strategy to promote Afrezza’s rapid-acting nature rather than its inhaled nature – we think this was a very smart move, considering the previous emphasis on the inhaled administration brought to mind lingering concerns among some patients and providers of the long-term safety of inhaling a growth hormone daily. The company filed with the FDA for an ultra-rapid-acting designation in 3Q16 based on data presented at ADA 2016, and a regulatory decision is expected by September 30 – this label claim would allow for even more direct advertising on the faster onset/offset of Afrezza vs. existing options for mealtime insulin. A blown-up model of the inhalation device was mounted on the back wall of the booth. Visitors could also view the small, patient-friendly device up close, while a video on loop showed how to insert 4-, 8-, or 12-unit cartridges into the inhaler. This, too, matches MannKind’s greater commercial strategy in that it distinguishes Afrezza from Exubera – this previous inhaled insulin product by Pfizer failed commercially, and it involved a notoriously clunky, burdensome, indiscrete inhalation device. Patient feedback on Afrezza has been extremely positive (or occasionally neutral) except for complaints about reimbursement, and we love the idea of a more rapid-acting mealtime insulin option out there to reduce hypoglycemia risk and improve quality of life for people with diabetes. While sales of Afrezza have been hurt by competitive dynamics (some recent stories we’ve heard about formularies have been incredibly troubling and we’re going to write some open letters on these in an effort to get more insulin to more people), we do hold out hope for increased uptake of the product, and we look forward to MannKind’s 1Q17 update on May 10.
Merck put up its standard booth in the exhibit hall, complete with a rotating overhead sign highlighting DPP-4 inhibitor Januvia (sitagliptin), posters showing how Januvia as an add-on to metformin achieves lower A1c, lower fasting plasma glucose, and greater postprandial glucose control, interactive monitors with patient case studies, and of course, a froyo stand. We can’t wait to see additional measures when they have an SGLT-2 and an insulin on the market – it’s not that long! Wow, what’ll things look like when they can offer smart insulin?
Novo Nordisk’s bustling main booth was positioned in the very center of the exhibit hall. Featuring plush white carpet and sleek wooden tables surrounding a (very popular) coffee bar, the floorspace was divided equally between three of the company’s most successful products: next-generation basal insulin Tresiba (insulin degludec), GLP-1 agonist Victoza (liraglutide), and the combination product Xultophy – launched in the US pharmacies just two days ago! Tresiba materials featured the product’s signature skydiving/parachute motif with the slogan “a proven A1c descent.” Data featured in the booth focused especially on the flexible dosing indication on Tresiba’s label and the fact that it is the only basal insulin pen with a max injection dose up to 160 units – this latter point is clearly part of Novo Nordisk’s efforts to position Tresiba for patients with type 2 diabetes and higher insulin requirements. Victoza materials highlighted the drug’s “3-for-1 benefits” – A1c efficacy, weight loss, and low rate of minor hypoglycemia – and emphasized that it is the #1 prescribed GLP-1 agonist globally. The messaging around Xultophy emphasized the combination product’s ability to “take glycemic control a step further” with the clinical benefits of both Tresiba and Victoza. Given Xultophy’s newly launched status (and indeed the existence of an earlier-to-market competitor in the US within this highly-anticipated new drug class, Sanofi’s Soliqua [insulin glargine/lixisenatide]) we were surprised that it wasn’t emphasized more prominently in Novo Nordisk’s booth. That said, management has noted that the company will prioritize Tresiba and Victoza individually for now, holding off on full-scale promotion efforts for Xultophy until there is more established familiarity around both of its component monotherapies. A separate, smaller booth toward the rear of the exhibit hall was devoted entirely to obesity medication Saxenda (liraglutide 3.0 mg), beckoning providers to “help your patients with obesity get the weight reductions they need.” The booth featured a photo of a women holding a larger pair of jeans – the classic “before and after” weight loss pose – with the phrases “excess weight,” “high cholesterol,” “large waistline,” and “high blood pressure,” emblazoned on the pants. Notably, the promotional materials referred to Saxenda as “the first and only GLP-1 agonist for chronic weight management” – emphasizing that obesity, like diabetes, is a disease that requires constant management.
Sanofi occupied a commanding booth at the very entrance of the packed exhibit hall, recognizable by its usual sleek white banner and overhead signs for its varied insulin analog offerings. In contrast to Novo Nordisk’s booth, which positioned its newly-launched basal insulin/GLP-1 agonist product Xultophy on equal footing with its more established products, Sanofi’s booth dedicated a majority of its square footage to Soliqua (insulin glargine/lixisenatide), as demarcated by the drug’s signature dark blue, purple, and gold color scheme. Launched in early January, Soliqua was the first basal insulin/GLP-1 agonist fixed-ratio combination to hit US pharmacies (Novo Nordisk’s Xultophy [insulin degludec/liraglutide] was FDA approved on the same day as Soliqua and launched just two days ago). The front walls of the booth displayed the clinical data for Soliqua and representatives were on hand to guide attendees through touchscreen displays of detailing Soliqua’s dosing and titration information. This messaging was largely centered on how to initiate for people hoping to intensify existing Lantus therapy – a smart move on Sanofi’s part given falling sales of flagship Lantus in the aftermath of its patent expiration and exclusion from formularies in favor of biosimilar insulin glargine Basaglar. The remainder of the booth was dedicated to Sanofi’s next-generation basal insulin Toujeo (U300 insulin glargine), with more touchscreen displays pointing to information on Toujeo’s efficacy in clinical studies and ease of use, touting Toujeo as providing “all day stability with an insulin of today.”
The Sanofi/Regeneron booth was positioned directly adjacent to Sanofi’s main booth, and PCSK9 inhibitor Praluent (alirocumab) took center stage. Throughout the booth was a motif of blue and green arrows, pointed down toward the ground to parallel Praluent’s LDL cholesterol-lowering action. Signage surrounding the booth’s perimeter emphasized Praluent’s efficacy and ease of use, posting large statistics boasting the drug’s “more than 60% LDL reduction” and the fact that “up to 80% of patients achieved their goal” when taking Praluent. With an eye toward personalization, Regeneron’s advertisements also emphasized the fact that Praluent comes in two different pens, a 75 mg/dl dose and a 150 mg/dl dose for “more power if you need it.”
Tandem’s simple booth showcased the remote-upgradable t:slim X2, and reps suggested that feasibility data for the predictive low glucose suspend (PLGS) device will be presented at ADA. Commented one: “It’s looking good.” (No surprise here; it uses a very proven algorithm based on the academic literature.) He also highlighted that the G5 integration is under FDA review and expected to launch this summer, and that working with FDA has been “amazing.” We’re looking forward to a dinner symposium entitled “The Journey to Closed Loop Control” with TypeZero CMO Dr. Daniel Cherñavvsky tomorrow night, where we’ll hopefully hear about the latest in Tandem/TypeZero’s clinical data and/or pipeline.
While the Valeritas booth was business as usual, showing the mechanical basal-bolus V-Go patch delivery device, the company has two impressive posters at this year’s AACE. This is yet another company that doesn’t get enough credit, in our view, for making it easier to get the right therapy into patients. Both posters show that V-Go use results in A1c reductions in people with long-standing uncontrolled type 2 diabetes: In the first retrospective analysis (n=103), type 2 patients who switched to V-Go experienced significant and sustained A1c reductions as well as reductions in the total daily dose of insulin. In the second (n=89), 70% of type 2 patients with A1c >8% achieved an A1c <8% and/or a reduction in A1c ≥1% after switching from usual care to V-Go. Again, mean total daily insulin dose was significantly reduced from baseline. These studies add to the growing data collection supporting the clinical efficacy of V-Go. Valeritas successfully went public on the NASDAQ earlier this year (market cap currently ~$44 million), and a rep told us that the IPO successfully raised $55-$60 million – we have yet to see a confirmatory press release, but the stock is indeed trading on the NASDAQ.
-- by Abigail Dove, Helen Gao, Brian Levine, Payal Marathe, Adam Brown, and Kelly Close