A Honky Tonk hello from Nashville, where we’re nearly halfway through AACE’s 24th Annual Scientific & Clinical Congress at the vaguely guitar-shaped Music City Center downtown. We’ve been impressed with the conference experience here so far: the beautiful two-year-old conference center was a bold bet by Mayor Karl Dean (who spoke at the opening session and persuasively asked attendees to spend money in his city) and the space is looking for conferences to fill it – take note, conference planners! In addition to the mayor, the opening session featured a performance from virtuoso harmonicist Mr. Buddy Greene who gave us a completely different take on the instrument by covering blues to Bach. As we mourn the loss of BB King tonight, we’re very happy to be in Nashville, a city with music emanating everywhere.
Diabetes drugs, tech, and obesity were all solidly featured in the day’s agenda. Read on below for our top ten highlights from the day, plus a briefing from the exhibit hall and more detailed coverage of a few presentations. Check out our day #1 highlights if you missed them and please see our preview for a look at the rest of the week.
1. Dr. Ed Damiano (Boston University, Boston, MA) provided a first-ever look at the Bionic Pancreas pivotal study design (6-12 months, n=480) and shared updated interim results from the recently completed 11-day multicenter study (from 35 of the 38 total patients).
2. At an Animas dinner event, Senior R&D manager Mr. Thomas McCann (J&J, New Brunswick, NJ) characterized the artificial pancreas “a priority for J&J Diabetes Care” – this was terrific to hear.
3. Dr. Irl Hirsch (University of Washington, Seattle, WA) called Abbott’s FreeStyle Libre a “game-changer” and Dexcom’s new Share Receiver “totally cool.” Dr. Hirsch’s comments reinforced Dr. Bode’s enthusiasm on Libre from yesterday; Dr. Hirsch did not forecast any timelines.
4. We heard commentary throughout the day on the impressive commercial success of SGLT-2 inhibitors along with the growing concerns about euglycemic DKA.
5. The promise of combining SGLT-2 inhibitors with other agents like DPP-4 inhibitors and GLP-1 agonists was another recurring theme of the day. We’ve written about this a lot, especially the SGLT-2/GLP-1 combo, which is getting lots of enthusiasm on the weight loss front.
6. At the exhibit hall: Toujeo (insulin glargine U300) was front and center at Sanofi’s booth; Novo Nordisk had booths for both Saxenda (liraglutide 3.0 mg) (where we learned new details on its savings programs) and for general obesity management; and as the hall’s largest company-sponsored display, Lilly’s booth devoted an entire wall to Trulicity (GLP-1 dulaglutide) and a smaller section to Glyxambi (empagliflozin/linagliptin – the first branded fixed dose combo – a DPP-4/SGLT-2 combo).
7. Dr. Irl Hirsch (University of Washington, Seattle, WA) suggested that biological “cures” for type 1 diabetes could be considered successful even if they do not lead to complete insulin independence. Hmmm …
8. Commentary on Toujeo at a Sanofi-sponsored CME breakfast included confidence in its nocturnal hypoglycemia benefit but uncertainty about the value of wholesale switching. The whole formulary thing is becoming a real nightmare for many doctors who don’t feel they really practice medicine anymore. There’re probably some patient advocacy opportunities here.
9. In a session on obesity pharmacotherapy, Dr. Caroline Apovian (Boston Medical Center, Boston, MA) stated that she sees a combination of medications and devices as the future of obesity treatment; we also heard additional commentary on specific obesity drugs that touched on the potential of Zafgen’s beloranib as well as drugs’ various degrees of clinical effectiveness.
10. Dr. Evan Stein (University of Cincinnati Medical Center, Cincinnati, OH) spoke positively about post-hoc outcomes analyses on PCSK9 inhibitors and speculated on their possible cost and treatment by payers. We’ll be hearing more about this, that is for sure. PCSK-9s are talked a lot about for now, related to familial hypercholesterolemia, or FH, for sure. We’ll get “an earful” on familial hypercholesterolemia at the upcoming EMDAC meeting, scheduled on the last day of ADA, June 9 – if you want a preview, see this excellent blog posting on this condition by FH patient advocate extraordinaire Cat Davis Ahmed of the FH Foundation. Reading it helped us understand this class better and made us even more confident about the overall commercial potential for PCSK-9s for Sanofi and Amgen and clinical potential for patients.
- Executive Highlights
- Top Ten Highlights
- Detailed Discussion and Commentary
- Opening Plenary
- Corporate Symposium: Combination Therapy in Type 2 Diabetes Management – Charting Courses for Success (Sponsored by AZ)
- Corporate Symposium: Overcoming Barriers in Diabetes Management with Individualized Treatment Strategies (Sponsored by Sanofi)
- Exhibit Hall
Top Ten Highlights
1. Dr. Ed Damiano (Boston University, Boston, MA) provided a first-ever look at the Bionic Pancreas pivotal study design (6-12 months, n=480), slated for 2016-2017 with a commercial launch ideally in 2018. As expected, the pivotal will assess efficacy/safety and chronic glucagon exposure. The first portion of the trial will randomize 320 patients to the Bionic Pancreas for six months and 160 patients to usual care (either MDI or CSII) monitored with a blinded CGM. Primary outcomes are A1c and the percentage of time spent <60 mg/dl during the last three months of each arm. These findings will be complemented by an investigation of a randomized selection of patients (n=107) on the Bionic Pancreas who will continue for an additional six months (“Continued Access Study”) to examine the effect of chronic glucagon in order to inform the chronic use indication. Notably, the Bionic Pancreas PMA will be submitted to the FDA as soon as the final patient completes the Bionic Pancreas arm (~nine months after the start of study) and in parallel with the Continued Access Study. The Agency is also pushing hard for Dr. Damiano to actually get the indicated age limit as low as possible (ideally less than 10 years)! This is true patient advocacy and we really, really salute this team. In Q&A, Dr. Damiano shared that existing partners include Xeris, Dexcom, and Tandem, though we don’t believe the latter is developing a dual-chamber pump near-term (if it were – what a great public/private partnership this would be – we wish some outside funding could come their way on this front). The pivotal trial, as a reminder, will use the Xeris glucagon, a dual-chambered pump with a built-in algorithm, and a Dexcom CGM sensor. By June 3, the NIH will decide whether to fund the pivotal trial as part of a major initiative for large outpatient artificial pancreas studies – we really hope to see this. While some believe glucagon is too controversial to use, we believe this is why it is called “research” – we can also say from personal experience that the glucagon enables algorithms that may suit some patients better (limited experience suggest that daytime blood glucose is driven down faster, which can be a real benefit for impatient patients used to doing this “in the wild” themselves, often unsafely).
- Dr. Damiano also shared updated interim results from the recently completed Bionic Pancreas 11-day multicenter study (from 35 of the 38 total patients), first seen at the GTC Bio Diabetes Summit 2015. For the first time, he shared details on glucagon usage in the Bionic Pancreas arm (~0.51 mg/day; half a rescue dose). As a reminder, patients had a mean blood glucose of 141 mg/dl (estimated A1c of 6.5%) on the Bionic Pancreas vs. 162 mg/dl (7.3% estimated A1c) on usual care, while time spent in hypoglycemia (<60 mg/dl) was reduced by more than two-thirds: 0.6% on the Bionic Pancreas vs. 1.9% on usual care. We believe, of course, that “usual care” in trials is also way better than in real life so in our view, these results actually are somewhat understated. Consistent with previous studies, the Bionic Pancreas did not significantly increase total daily insulin dose: 0.63 units/kg/day usual care vs. 0.66 units/kg/day BP, virtually the same (but given at much better intervals, again, in our opinion).
2. At an Animas dinner event, Senior R&D manager Mr. Thomas McCann (J&J, New Brunswick, NJ) characterized the artificial pancreas “a priority for J&J Diabetes Care.” Though there were no timing updates or highly notable specifics, Mr. McCann suggested that a hypoglycemia-hyperglycemia minimizer (HHM) is indeed still in the works. The company presented a small closed-loop feasibility study at ADA 2013 (n=20) on this front; an even smaller trial presented at ADA 2014 (n=12) tested only predictive low glucose suspend. Given that the ADA 2014 study was less ambitious, we had been losing hope that Animas was really moving this project forward. This evening’s dinner gave us renewed confidence, and perhaps things will move forward faster now that the Animas Vibe is out in the US and Dexcom is pushing pump partners harder on the automated insulin delivery front (see our Dexcom 1Q15 coverage). We hope fervently that J&J CEO Alex Gorsky (who is always talking on Twitter about topics such like J&J giving lots of money to broad causes like “Operation Smile”) sees how well the Invokana franchise is doing and diverts some of the profits to medical devices. (This area is technically overseen by Consumer Head Sandra Peters though the P&L goes through Medical Devices – a nontraditional arrangement, but we hope that Ms. Peters also lobbies for more diabetes medical devices funding – she used to run blood glucose monitoring at Bayer.) From an outside perspective, this artificial pancreas project has moved at a glacial pace, considering Animas originally signed the partnership with JDRF in 2010. We hope JDRF CEO Derek Rapp can also add some pressure – look at the great outcomes at BD stemming from this JDRF and Helmsley Charitable Trust work! Undoubtedly, Animas certainly must do something in automated insulin delivery to stay competitive with Medtronic, Tandem, and Insulet in the near-term, who have all publicly committed to active R&D projects on this front – Medtronic in particular threw down the gauntlet with expectations to launch its MiniMed 670G in the US by April 2017 (we are on record doubting this timeline can be met though we appreciate the company being ambitious). Meanwhile, the Bionic Pancreas team expects a 2018 commercialization of its system (pivotal trial in 2016-17), and Bigfoot Biomedical plans to be in a pivotal trial by the end of 2016. Exciting times continue, and of course we hope very much the trial designs can be standardized.
3. Dr. Irl Hirsch (University of Washington, Seattle, WA) called Abbott’s FreeStyle Libre a “game-changer” and Dexcom’s new Share Receiver “totally cool.” On the former, he suggested that Libre’s factory-calibration and accessible pricing (he estimated the cost at ~$5 a day) makes it a very attractive option across the board. Interestingly, Dr. Hirsch does not expect the technology to generate as much excitement in the US as it has in the EU due to the wider accessibility of traditional CGM stateside, though he still expects it to appeal to both type 1 patients and insulin-treated type 2s – we’d note that the CGM market is still very underpenetrated right now in the US, especially in type 2, so we believe Libre does have plenty of upside. We also believe that there would be broad interest in it from virtually any patient with type 2 – obviously we are unsure if it would be reimbursed, but given how poorly so many type 2 patients are doing, we think this would be a boon for many. We also see it driving therapeutic change for so many patients with type 2 and making doctors’ jobs much easier. An informal poll of the audience revealed that only ~10% had previously heard of Libre – this was not too surprising, since Abbott has done a good job of limiting the marketing, awareness, and webshop access to European audiences. Dr. Hirsch also offered a positive take on Dexcom’s new Share receiver with built-in Bluetooth (“this is totally cool!”), noting that the use of the cloud may have a profound impact on type 1 diabetes, especially in preventing hypoglycemia. Dexcom has pushed the boundaries on connectivity, and we have high hopes that Gen 5 will be equally well received (currently under FDA review, with approval expected by end of year). More broadly on CGM, Dr. Hirsch suggested that MARDs have improved in recent generations, but need to be better and solidly in the “single digits” to enable the success of closed-loop systems – we’d note that Dexcom’s Software 505/G4AP algorithm has a MARD of 9.0%, so it’s definitely in Dr. Hirsch’s ballpark.
- Touching on data downloading, Dr. Hirsch said that he is a big fan of Tidepool. He believes that Medtronic’s CareLink is the current “gold standard” in the field, though he forecast that this could easily change in the near future. Indeed, while a poll of the audience revealed that 50% download data from pumps/CGM/BGM, Dr. Hirsch predicted that “all of you will raise your hand in five years!” (Less than ~5% had heard of Tidepool specifically, though Blip is still in a closed beta.) Dr. Hirsch emphasized that Tidepool’s open-source, non-profit model is compelling, not to mention the recent grant from the Helmsley Charitable Trust as a strong vote of confidence in the organization and its “impressive” founder and CEO, Mr. Howard Look.
4. We heard commentary throughout the day on the impressive commercial success of SGLT-2 inhibitors along with the growing concerns about euglycemic DKA. At a product theater for J&J’s Invokana (canagliflozin), Dr. James Gavin (Emory University, Atlanta, GA) noted that his prepared slides heralding the product’s commercial success were already out of date: Invokana has now reached over 4 million prescriptions since its launch and achieved over 80% commercial and Medicare coverage. In a talk later in the afternoon, Dr. Irl Hirsch (University of Washington, Seattle, WA) offered similar sentiments, sharing projections suggesting that Invokana will be a $2-$3 billion drug by 2020 – we see that as a conservative estimate though it depends largely on how ambitious J&J is on the formulary front (it also assumes euglycemic DKA stays manageable – most if not all cases to date have been associated with Invokana – unsurprising given its dominance in the US). Speakers at both sessions characterized the class as very appealing to patients and providers – Dr. Daniel Einhorn (Scripps Health, La Jolla, CA) said they were “one of the most adhered to medications I’ve ever used” – oral administration can’t hurt, and weight benefits are highly motivating for patients.
- On the less positive side, concerns about euglycemic DKA were also raised at several events. This phenomenon has rapidly emerged as a significant safety issue since KOLs including Dr. Anne Peters (USC, Los Angeles, CA) and Dr. Irl Hirsch and Dr. John Buse (UNC) first began drawing attention to it at ENDO in March (Dr. Peters before that). Three attendees at the product theater submitted questions on the subject, to which Dr. Einhorn responded only that there have been anecdotal reports, mainly in type 1 diabetes, and that the mechanism is not at all clear. Echoing Dr. Ralph DeFronzo’s (University of Texas Health Science Center, San Antonio, TX) remarks from day #1 of AACE, Dr. Hirsch suggested that the increase in glucagon production with SGLT-2 inhibitors may be the culprit; the hypothesis is that elevated glucagon can push the liver into a ketogenic state, particularly in the context of low insulin levels. Dr. Peters offered the strongest words of caution on the subject at an AZ-sponsored evening symposium, advising providers to refrain from off-label use of the class in type 1 diabetes until the risks are better understood. While many unanswered questions remain around this issue, it is clearly a significant clinical concern – an informal poll during Dr. Hirsch’s talk indicated that ~1/3 of the audience had prescribed SGLT-2 inhibitors off-label in type 1 diabetes.
- At the AZ symposium, Dr. Vivian Fonseca (Tulane University, New Orleans, LA) shared that the EMPA-REG OUTCOME CVOT of Lilly’s Jardiance (empagliflozin) has been completed and confirmed that results are expected at EASD. We first heard about this expected timeline from Dr. Silvio Inzucchi (Yale University, New Haven, CT) at ENDO and are glad to hear more definite confirmation. This will be the first CVOT for an SGLT-2 inhibitor to report results; the next trial, CANVAS (for Invokana) is not scheduled to report until 2017.
5. The promise of combining SGLT-2 inhibitors with other agents was a recurring theme of the day. During the Invokana product theater, Dr. Einhorn highlighted the complementary mechanisms and strong efficacy of SGLT-2 inhibitor/DPP-4 inhibitor combinations, which are now finally on the market following the launch of Lilly/BI’s Glyxambi (empagliflozin/linagliptin). During his afternoon talk, Dr. Hirsch discussed the even more exciting prospect of GLP-1 agonist/SGLT-2 inhibitor combinations, which he believes could potentially have additive or even synergistic efficacy and powerful effects on body weight – of course, as Dr. Fonseca noted during the AZ symposium, these combinations also add an additional layer of complexity for patients compared to oral fixed-dose combinations. He highlighted the ongoing trial of combination therapy with Invokana and Novo Nordisk’s Victoza (liraglutide) led by Dr. DeFronzo; AZ is also currently conducting a trial investigating combination therapy with Bydureon (exenatide once weekly) and Farxiga (dapagliflozin). Dr. Hirsch also noted that this combination could potentially eliminate the risk of euglycemic DKA, as the GLP-1 agonist component would hopefully blunt the increased glucagon production induced by the SGLT-2 inhibitor that is believed to be a cause of the phenomenon (see above). On the negative side, he cautioned that cost could be a major barrier with these two very expensive drug classes – the success of a future combination product would certainly depend heavily on the level of reimbursement, though we imagine that such an impressive clinical profile (if the expectations are borne out in clinical trials) would be very appealing to payers.
6. The AACE exhibit hall featured most of the big names in drugs, tech, and obesity. Sanofi’s booth enjoyed prime placement at the front of the hall and had a large-scale mockup of the Toujeo (insulin glargine U300) SoloStar Pen up front alongside displays on Sanofi’s new basal insulin. Displays for inhaled insulin Afrezza were placed in the back of the booth – this was a bit surprising from our view and we continue to hope it will receive the attention it deserves given that Sanofi is also very focused on the Toujeo launch (we see so much overlap for these two drugs to be used together though realistically, for now, Toujeo is likely being marketed to many more HCPs than Afrezza). We look forward to seeing the Afrezza DTC campaign and believe this will be a sleeper success, ultimately, as long as it receives the resources it deserves. Novo Nordisk had a significant obesity presence, with one booth focused on the recently launched Saxenda (liraglutide 3.0 mg) and the second focused on general obesity management. Most notably, we learned just-released details on Saxenda’s savings program (price of $30/month for commercially covered patients and savings of $200/month for out-of-pocket paying patients) and got our hands on the new FlexTouch pen. Lilly’s plush carpeted booth – the largest company-sponsored display of the exhibit hall – devoted an entire wall to new GLP-1 agonist Trulicity (dulaglutide) and a comparatively small section to the newly launched Glyxambi (empagliflozin/linagliptin). However, representatives throughout the exhibit were eager to discuss the new combination; one rep shared that Lilly/BI are seeing Glyxambi prescribed primarily as a third-line option after metformin and a DPP-4 inhibitor or for patients already taking both an SGLT-2 inhibitor and a DPP-4 inhibitor as separate pills – this is somewhat distinct from comments we heard during Lilly’s 1Q15 update.
7. Dr. Hirsch suggested that biological “cures” for type 1 diabetes could be considered successful even if they do not lead to complete insulin independence. He explained that his thinking in this area has changed dramatically since his days as a young researcher in the 1980s when the widespread expectation was that type 1 diabetes would be cured within the next five years. (We believe there is some variance here – we certainly know patients who did not anticipate a cure in the 1980s – but some certainly also did receive misinformation on this.) After seeing many patients derive enormous benefit from a small amount of residual insulin production (whether naturally or after a “failed” pancreas transplant), he now believes that even reducing insulin doses by ~50% with a cell replacement therapy could lead to meaningful improvements in quality of life – this would be especially true if the therapy reduced glycemic variability alongside lowering glucose. Setting realistic expectations for success will be very important as cell-based therapies like ViaCyte’s VC-01 move closer to reaching patients, as we imagine there is plenty of room for disappointment if these therapies fall short of being complete cures. We heard similarly pragmatic commentary from Dr. Alexander Fleming (Kinexum, Harpers Ferry, WV) at the GTC Diabetes Summit focused primarily on regulatory expectations for cell-based therapies, and we hope to hear much more as these therapies progress through clinical trials.
8. Speakers at a Sanofi-sponsored breakfast symposium presented a balanced view of Sanofi’s new basal insulin formulation Toujeo (insulin glargine U300). None of the panelists suggested that they are rushing to use Toujeo in all their patients initiating basal insulin or currently on Lantus – this is undoubtedly partly an issue of some patients doing well on Lantus currently and some HCPs not wanting to deal with more administrative hassles and burdens (even if Toujeo on balance would be better for some patients). We don’t have a clear sense of whether patients new to insulin are being charged an arm and a leg (over Lantus) or not. Dr. Lisa Tannock (University of Kentucky, Lexington, KY) noted that at this point, all we know about Toujeo (based on fairly short-term clinical studies) is that there is a nocturnal hypoglycemia benefit and more borderline overall hypoglycemia and weight benefits vs. Lantus. Although she does see Toujeo as an improvement over Lantus, she suggested that if a patient is doing well on Lantus there is little reason to switch to Toujeo. Dr. Zachary Bloomgarden (Mount Sinai School of Medicine, New York, NY) expressed some uncertainty over how useful Toujeo will be relative to other alternatives for patients not at control on Lantus alone, including GLP-1 agonists. Dr. Tannock did note that Toujeo represents a good option for highly insulin resistant patients as the dosing is more straightforward with Toujeo’s pen than with Humulin U500 vials. On access, Dr. Tannock noted wryly that the choice between Toujeo and Lantus is more a matter of patients’ insurance; Dr. Bloomgarden wondered aloud whether the future introduction of biosimilar insulin glargine may further constrain access to premium options like Toujeo. We are eager to see how the conversation on Toujeo vs. Lantus develops in symposia and exhibit halls at coming meetings like ADA.
9. In a session on obesity pharmacotherapy, Dr. Caroline Apovian (Boston Medical Center, Boston, MA) stated that she sees a combination of medications and devices as the future of obesity treatment. Fielding a question on the potential of combinations such as phentermine/lorcaserin, she noted that she foresees not only combinations of medications but also combinations of medications and devices; specifically, she expressed hope that a combination of drugs and devices could produce weight loss comparable to that achieved with bariatric surgery. In her presentation, she noted the upcoming emergence of many obesity devices, including the endoluminal barrier, Gelesis’ Gelesis100 pill (a pill that soaks up water and expands in the stomach, which she commented “may come out shortly”), and intragastric balloons. Separate from Dr. Apovian's presentation, in the opinion of Close Concerns, while we do not see any currently available obesity devices as holding great potential (see our coverage of the approval of EnteroMedics’ VBLOC Therapy), we would agree that combinations that utilize different targets will likely provide more success in weight management in the future – please read our coverage of last week’s European Congress on Obesity (ECO) to see similar sentiments on combination therapies.
- On the drug front, Dr. Apovian pointed out that if Zafgen’s beloranib does not have deleterious side effects, it may “really be a game changer.” Indeed, we see beloranib’s mechanism of action (it alters fat metabolism by inhibiting MetAp2) as one that differentiates it from the many centrally acting drugs currently available. As a reminder, beloranib is in phase 2/3 development and has so far shown solid safety and efficacy data in hypothalamic-induced associated obesity and severe obesity.
- During Q&A in a subsequent session, Dr. Joshua Thaler (University of Washington, Seattle, WA) provided commentary on his clinical experience with obesity drugs. He pointed out that he has seen significant variability in weight loss with liraglutide: some people respond dramatically while others do not experience much weight loss at all – this reflected Dr. Apovian’s earlier point that providers should not expect the average weight loss produced by a drug in clinical trials to predict their patients’ experience, which is heavily dependent on whether or not the individual responds to the drug. On the other hand, Dr. Thaler added that he has had “a lot of luck” with Vivus’ Qsymia (phentermine/topiramate) as he has seen many patients successfully respond to the drug. He described Orexigen/Takeda’s Contrave (naltrexone/bupropion) as an intermediate option and stated that Arena/Eisai’s Belviq (lorcaserin) is not very potent in terms of weight loss but has a benign side effect profile (this is similar to commentary we have heard in the past). Overall, when thinking about providers’ different characterizations of obesity pharmacotherapies, we see the ability to forecast which drug will be effective in which patients as an increasingly important question. Unfortunately, we do not see this being answered anytime soon due to the disappointing progress on genetic analysis in obesity: the loci that have been identified so far contribute to only a very small amount of BMI variance.
10. Dr. Evan Stein (University of Cincinnati Medical Center, Cincinnati, OH) provided some key commentary on PCSK9 inhibitors in the main conference session on the exciting new drug class for LDL lowering. Ever since the presentation of post-hoc phase 3 analyses on Sanofi/Regeneron’s Praluent (alirocumab) and Amgen’s Repatha (evolocumab) showing roughly 50% reductions in CV events (although based on few events), we’ve been interested to hear where the conference commentary would fall on the spectrum between excitement and caution. Dr. Stein was not afraid to be optimistic, noting that the Kaplan-Meier curves for both Praluent and Repatha were nearly superimposable and the divergence from the placebo group was found after just a few months., He contrasted this with statins where it took nearly ten years after phase 2 and 3 to get similar data. However, in his conclusion he was slightly more guarded with his words, suggesting only that the early CV analyses have been “moving in the right direction.” The outcomes trials for the first three PCSK9 inhibitors alone plan to collectively enroll 71,500 patients, meaning that unequivocal and definitive answers on outcomes are on their way. During Q&A, he shared that his best guess, based on other monoclonal antibodies used for chronic diseases, is that the drugs will cost around $10,000-$12,000 per year (we wouldn’t hold him to this but it is helpful to hear guesses) and that in the coming era of multiple generic statins and generic ezetimibe, payers will put hurdles in place to make sure that providers exhaust other options before going straight to PCSK9 inhibitors.
Detailed Discussion and Commentary
Ed Damiano, MD (Boston University, Boston, MA)
Dr. Ed Damiano’s plenary lecture (attended by ~1,800 endocrinologists!) provided a comprehensive overview of the Bionic Pancreas from conception through planned commercialization. The majority of his talk was delivered at a high level – geared toward the broader endocrinology audience – though was headlined by our first-ever look at the group’s new pivotal trial design (12 months, n=480) and an update on the timing of the planned FDA submission (nine months after the start of the pivotal and in parallel with the chronic glucagon arm of the pivotal study). The team is still on track to conduct its pivotal in 2016-2017 with commercial launch in 2018 – we’ve been impressed with the team’s ability to stay very nearly on a schedule originally laid out in 2012 (We say “nearly” because the original plan estimated a commercial launch in late 2017, though the pivotal trial was expected to be shorter; the need for chronic glucagon exposure has now lengthened the timing a bit). Notably, he concluded by sharing updated interim results from the recently completed Bionic Pancreas 11-day multicenter study (from 35 of the 38 total patients), first seen at the GTC Bio Diabetes Summit 2015. He shared for the first time details on glucagon usage in the Bionic Pancreas arm (~0.51 mg/day), without a corresponding increase in insulin dose. We continue to follow glucagon and insulin usage closely in light of recent criticisms that the Bionic Pancreas algorithm is “aggressive.”
- The Bionic Pancreas pivotal trial will assess the system’s efficacy/safety and chronic glucagon exposure over 12 months. The first portion of the trial will randomize 320 patients to the Bionic Pancreas for six months and 160 patients to usual care (either MDI or CSII) monitored with a blinded CGM. Primary outcomes are A1c and the percentage of time spent < 60 mg/dl during the last three months of each arm. These findings will be complemented by an investigation of a randomized selection of patients (n=107) on the Bionic Pancreas who will continue for an additional six months (“Continued Access Study”) to examine the effect of chronic glucagon in order to inform the chronic use indication. The 160 patients randomized to the original control arm will get to follow their six months of usual care with a three-month “Incentive Study” on the Bionic Pancreas (as a way to motivate their participation). We like the idea, since many will be disappointed to end up in this study’s control group – it should indeed motivate participation and help gather even more data in a streamlined way.
- Dr. Damiano shared that the Bionic Pancreas PMA will be submitted to the FDA as soon as the final patient completes the Bionic Pancreas arm (~nine months after the start of study) and in parallel with the Continued Access arm. It is great to see the FDA’s forward-thinking approach here and willingness to expedite the process. The device side of the Agency has been increasingly patient-centered in the past year (e.g., declassification of secondary CGM data) and it is great to see similar appreciation for the value of the Bionic Pancreas from the FDA’s drug wing.
- Dr. Damiano presented the latest interim results from the recently completed Bionic Pancreas 11-day multicenter study. Patients had a mean blood glucose of 141 mg/dl (estimated A1c of 6.5%) on the Bionic Pancreas vs. 162 mg/dl (7.3% estimated A1c) on usual care. In our view, “usual care” would be better in this trial than in “real life.” Dr. Damiano also made a point of calling out the narrow inter-patient variability on Bionic Pancreas (SD: 10 mg/dl) vs. on usual care (SD: 29 mg/dl). This is consistent with previous trials where we have seen the Bionic Pancreas’ ability to bring patients into a narrow range despite patients’ wildly varying day-to-day insulin demands. Time spent in hypoglycemia (<60 mg/dl) was reduced by more than two-thirds: 0.6% on the Bionic Pancreas vs. 1.9% on usual care. Notably, these are motivated patients in superb control to begin with, and we are impressed to see that the Bionic Pancreas is able to bring them safely into even tighter control (indeed, one thing we have heard is that someone with a 5.5% A1c went into the trial – and did better!).
- Dr. Damiano stressed that the Bionic Pancreas has not delivered more insulin than usual care [0.63 units/kg/day usual care vs. 0.66 units/kg/day BP] nor has there been excessive glucagon usage (~0.51 mg/day bionic pancreas). This is notable in light of recent criticisms that the Bionic Pancreas’ use of insulin and glucagon is “aggressive.” At ATTD 2015, Dr. Roman Hovorka reiterated concerns that in the Beacon Hill study, participants had a 32% increase in their daily insulin dose during closed-loop. He implied that the increase results from a “stop-and-go” approach to hormone administration that, in his eyes, aggressively doses insulin and depends on glucagon to counteract that “excessive” administration. So far, it appears that the multicenter trial has differed from the data gathered in Beacon Hill, and perhaps these criticisms will be less of a concern going forward.
- During a follow-up press conference, Dr. Damiano shared that the group’s current plan is to pursue an indication for the Bionic Pancreas in patients 10 years and older, though he is hoping this can be pushed lower. Apparently, the FDA is actually encouraging the group to aim for a younger indication as they have acknowledged that the Bionic Pancreas will likely be used off-label in the younger population if not indicated. The Agency would rather have the safety data and official indication than have patients use the device off-label – a very pragmatic take in our view. As a reminder, the Bionic Pancreas has been tested in patients as young as six years old (Summer Camp Study 2014).
Q&A from Dr. Damiano’s Press Conference
Q: Can you talk about plans for establishing secure cybersecurity?
A: This is something that the medical device industry hasn’t handle well until now. We have a person dedicated to working on that. We are working on ways to minimize risk. We are going to have as secure system as we can.
Q: What is on your possible list of things that may go wrong?
A: Let me be clear – we’re never going to build a system where we obviate every challenge. There will be times when things go wrong. Things go wrong for airplanes. When you put your life in the hands of a device, there will be cases when things go wrong. You try to make a list and mitigate these things as best you can. But circumstances will happen. However, I would remind you that you’re dealing with an at-risk population to begin with where things are already going wrong all the time. We want to reduce that to zero. Obviously, and we’ll do our best.
Q: When might this be available?
A: I would estimate 2018. I was hoping for the fall of 2017, but because of certain extenuating circumstances, it’s looking like 2018. The pivotal trials were going to be six months, but now they are one year because we are looking for a new indication for glucagon. We need a chronic use indication. We have to have some subset exposed for an additional six months. The FDA really wants to see people on this device for a year. However, to expedite the process of getting this into patient hands, the FDA has offered to let us submit the PMA after the six-month RCT study is over. The chronic glucagon patients will carry on, while the application is looked at. The FDA is really looking to help, but that extra six months is going to push us into 2018.
Q: What ages are you looking to get this indicated in?
A: We’ve proposed ages 10 and above. We may go lower than that. The FDA is really encouraging us to push that as low as we can. They know that this is going to be used off label, so they are looking to push this as low as possible.
Q: Is this dependent on funding from the NIH?
A: Yes. I have a proposal in front of them. Ask me after June 3rd .
Q: Can you talk more about the age indication? What would you like to propose?
A: I would like to get the Bionic Pancreas indicated for ages six and above. Our proposal says ten, but we’d like to get to 6. The FDA has said that they want us to test this in patients as young as possible. After all, I have managmed a child with type 1 diabetes when he was one year old. It’s challenging. As a parent, you are going to use this because it works. The FDA knows that so they’re pushing us to get it down.
Q: Can you talk about your commercial development? What companies are you involved with?
A: I can’t answer that fully. We’re working with investigative collaborators. The companies I can name are Dexcom, Tandem, and Xeris.
Q: Can you explain the secrecy?
A: I think there are times when it’s approrpriate to reveal what the platform looks like, and there are times when it’s not appropriate. We have relationships with partners who do not want their involvement revealed at this time.
Q: Are there other group working on closed-loop systems?
A: Yes. There are other academic groups working on it, though we don’t know about their industry collaborators either. There are industry companies working on proprietary systems too.
Q: Can you estimate the cost of the Bionic Pancreas?
A: I can give you an estimate. The components of the Bionic Pancreas are similar to what is available on the market. It’s a two-chambered pump not a single chamber, so it will be a bit more expensive than that. That’s a ballpark, and we’re looking to get it down. The real cost is in the consumables. You’ll have to change CGM sensor weekly. Fortunately, private payers do reimburse for CGM. I’ll be clear – this does not work without a reimbursement model. That’s a very big discussion that needs to happen. The reimbursement part is not a trivial problem.
Corporate Symposium: Combination Therapy in Type 2 Diabetes Management – Charting Courses for Success (Sponsored by AZ)
Best Practices with Long-Acting GLP-1 RAs, Short-Acting GLP-1RAs, and DPP-4 Inhibitors
Vivian Fonseca, MD (Tulane University, New Orleans, LA)
Dr. Vivian Fonseca gave a broad presentation on incretin-based therapies, including some of the newer options in the GLP-1 agonist class. He saved some of his most positive commentary for Intarcia’s implantable exenatide mini-pump ITCA-650, stating enthusiastically that taking the challenge of adherence out of patients’ hands is a great way to treat chronic disease. The greater efficacy and benign side effect profile relative to Byetta (the same exenatide molecule administered twice daily) suggests the benefits of slow release GLP-1 agonist administration. Although he presented the results of a number of GLP-1 agonist head-to-head studies, he argued against choosing agents based on efficacy alone. Using AZ’s DURATION-6 trial as an example, he noted that although Novo Nordisk’s Victoza (liraglutide) came out ahead in terms of A1c, Bydureon caused less nausea, which could be the deciding factor for patients for whom tolerability is more important. Switching over to DPP-4 inhibitors, Dr. Fonseca characterized Lilly/BI’s Tradjenta (linagliptin) as the “drug of choice” for patients with CKD due to its non-renal route of excretion. In line with a wave of comments we’ve heard recently, he is very positive on the combination of GLP-1 agonists and SGLT-2 inhibitors.
Corporate Symposium: Overcoming Barriers in Diabetes Management with Individualized Treatment Strategies (Sponsored by Sanofi)
Meeting Targets with New and Emerging Therapies Added to Basal Insulin
Lawrence Blonde, MD (Ochsner Medical Center, New Orleans, LA)
In Dr. Larry Blonde’s presentation on possible options for patients not at control with basal insulin, GLP-1 agonists came out as a favorite. In fact, Dr. Blonde noted that for many type 2 diabetes patients GLP-1 agonists may be the better choice as a first injectable – after all, head-to-head phase 3 trials show that basal insulin is no better in terms of A1c (or weight or hypo) and some trials even show GLP-1 agonists coming out ahead. The common wisdom is that for patients not at control on orals, insulin may be best for patients with very high A1cs due to its higher efficacy ceiling. Dr. Blonde agreed with that notion but suggested that the A1c threshold may be higher than some might expect: post-hoc analyses of head-to-head trials of basal insulin vs. GLP-1 agonists show that even patients with starting A1c as high as 9%-9.5% did at least as well with a GLP-1 agonist. It isn’t just Dr. Blonde who views GLP-1 agonists favorably as a starting injectable: during a show-of-hands poll, audience members favored GLP-1 agonists over basal insulin by at least a three-to-one margin. At the very end of his talk, Dr. Blonde put in a good word for Sanofi’s new inhaled insulin Afrezza. He stuck pretty closely to the script of the product label but did put Afrezza squarely in the win column for weight and hypoglycemia in a trial (based on a trial vs. premixed Biaspart (70/30)).
Panel Discussion – Selected Highlights
Q: So which patients do you start on insulin glargine U300?
Dr. Tannock: I have had a few patients I have switched to U300. I use it in my patients who report frequent nocturnal hypos because that’s where I think the data is most robust. With any new product on the market, the decision is largely in payers’ control. But it is individuals having hypos with U100 where I’d consider U300.
Q: When you need to start a patient on injectable therapy, by a show of hands, who goes to insulin first, and who uses GLP-1 agonists first?
[Attendees preferring GLP-1 agonists outnumbered those preferring insulin by around three to one]
Dr. Blonde: Whenever you ask an endocrinologist a question, the most frequent answer is it depends. All other things equal, GLP-1 agonists are the best first injectable.
Dr. Bloomgarden: We fail to realize how much better endogenous insulin is than exogenous. The beta cells deliver insulin primarily to the liver. Portal insulin levels are two to four-fold higher than in the periphery. When we give exogenous insulin, we alter that balance in a deleterious fashion, which increases adipogenesis and changes lipid levels. Sulfonylureas allow more endogenous insulin but they’re glucose insensitive which makes the benefit more tenuous. With the onset of incretin therapy, you get endogenous insulin to the liver first, so it’s working in the right fashion. That’s an underappreciated reason why these are better drugs.
Q: Do you use C-peptide to decide whether to use basal insulin vs. GLP-1 agonists?
Dr. Bloomgarden: I think that as a clinician, measuring insulin and C-peptide is rarely helpful. We really have a good sense of the degree of a patient’s insulin secretory defect based on their clinical and glycemic characteristics. Although conceptually you could say that if someone has low C-peptide then they would be more in need of exogenous insulin, as Larry said, for this audience, I think that all of you will know that well before the time you get the result of the C-peptide back from the lab.
Dr. Blonde: The other reason I agree with you is that C-peptide is only helpful if the value is high. If a patient has hyperglycemia, C-peptide may be low, but if you lower the hyperglycemia then it may come back up. It’s not that helpful clinically.
Q: We saw in the EDITION trials that there was a need for a greater insulin dose with Toujeo? Why, and how much of a dose increase was needed?
Dr. Tannock: I don’t remember the difference, but despite the difference there was less nocturnal hypoglycemia and less weight gain. The flip side is increased cost with more units.
Dr. Moghissi: It is about a 10%-15% increase, I think. It is because you have a more concentrated depot.
Q: Is dulaglutide approved for use with basal insulin?
Dr. Blonde: The data is good when used with rapid-acting analogs, but at present dulaglutide has not been studied with basal insulin.
Q: Could you talk about bone health with SGLT-2 inhibitors?
Dr. Bloomgarden: I think that there is interesting data on bone health with these agents, but nothing is conclusive in the way that TZDs were shown mechanistically and in clinical trials to adversely impact bone health. We need to keep aware of this, but I don’t think that this truly constitutes something that is at the level of a clinical issue at the present time.
Q: We are getting lots of questions about Toujeo’s clinical applications, because it is longer acting and has a flatter profile. When should we switch from U100 to U300? Is the increment of the benefit the same as from NPH to insulin glargine?
Dr. Tannock: One of the issues is that we have relatively short-term studies only. It’s the same insulin as Lantus but more concentrated. We have no outcomes data on long-term effects. All we have to go on is a decrease in nocturnal hypoglycemia. If a patient is doing well on U100, why change? As we get more data on U300 that may change. Right now we see fewer nocturnal hypoglycemia and trends towards less daytime hypoglycemia that bordered on significant. Also, there was less weight gain. That latter factor is something we may want to consider for patients who are struggling with their weight. However, often the decision to try Toujeo is not my choice – it’s up to payers.
Dr. Blonde: I am glad to see the field moving away from the term “minor hypoglycemia,” because I have seldom seen a patient who has had a hypoglycemia episode that they consider minor. Often times, clinicians may not be aware that their patients are experiencing these. Now that there may be options that can further improve the benefits of basal insulin analogs, with new analogs that have even lower hypoglycemia risk, it behooves us to ask in more detail whether our patients have been experiencing hypos that they have not been bringing to our attention.
Dr. Bloomgarden: It is important that if patients are having nocturnal hypos, you have to reassess and see if you are overusing basal insulin. If so, you can try workarounds like going to basal bolus or a basal plus a GLP-1 agonist. I don’t know yet how useful insulin glargine U300 is going to be within the overall set of choices, but it may offer a bit of an option. With payers I don’t know – with biosimilar insulins coming we may be forced to never use it.
Q: How do you divide the dose when starting U500?
Dr. Tannock: There’s no study other than that single study. I individualize it based on when patients eat.
Q: What is the cheapest insulin?
Dr. Tannock: It depends on where you practice. Insulin costs differ at different institutions. We pass on NPH regular 70/30 at a wholesale cost of $9 a bottle. That’s by far the cheapest until you get up to very significant doses. On a per unit basis, there was a time when U500 was by far the cheapest. Now it’s about 9 to 10 cents per unit, which is on par with most analogs. It varies pharmacy to pharmacy, so I tell patients to shop around. For many the break point is 300 units per day where U500 becomes cost-effective.
Dr. Bloomgarden: In people who are insulin sensitive, pens become less expensive if someone uses ~15-20 units a day. They’re wasting a huge amount if they buy a bottle. That’s an important effect for patients with type 1 diabetes. It’s not relevant to most patients with type 2 diabetes.
Q: At what level do you consider the insulin receptors to be saturated?
Dr. Tannock: The simple answer is no. You keep titrating until you get there. Some patients have insulin receptor defects, but that’s very rare. For most patients, you’ll get an effect when you hit the dose you need.
Dr. Blonde: I showed a study where adding exenatide to U500 didn’t make a difference. There’s another study where liraglutide did make a difference, but it was small and poorly controlled. There should be more studies in populations using U500 to see whether other agents like GLP-1 agonists might be helpful.
Abbott: Abbott’s classic yellow signage quickly drew our attention as we approach the middle of the exhibit hall. The relatively large booth focused on the company’s FreeStyle InsuLinx product line, though representatives did offer optimistic commentary on the recently launched Precision Neo BGM. As expected, representatives did not comment on a timeline for FreeStyle Libre in the US. We were interested to hear that the representatives had gotten a handful of visitors to the booth asking about Libre, suggesting that word of the product’s EU popularity is beginning to spread stateside. We believe that at ADA, Abbott Diabetes Care would be smart to show its Precision kits measuring ketones – this is really needed for any type 1 taking SGLT-2s off label – and far more education on ketones in general is needed given that “hundreds” of patients have experienced the dreaded “euglycemic DKA” to date, according to Dr. Anne Peters.
AstraZeneca: AZ’s booth gave essentially equal attention to all of its diabetes products – somewhat of a contrast from the heavy emphasis on Farxiga (SGLT-2 dapagliflozin) and the new Bydureon (GLP-1 once-weekly exenatide) pen in the company’s display at ENDO. The Bydureon pen did receive some extra promotional attention, with representatives eager to pull attendees aside for demonstrations on their way to the frozen yogurt stand. While the pen is certainly an improvement over the old vial-syringe system, it still does look a tiny bit clunky when compared to the Trulicity pen across the aisle at Lilly’s booth – clearly Lilly learned a lot from Amylin in developing this product. However, there’s a lot of room for success here among multiple companies –the Trulicity launch is going well and there is stronger-than-ever uptake of the Bydureon pen and franchise since its launch. We think one reason why is that popularity of SGLT-2s is actually driving this since the two seem to work well in combination (more satiety coming from GLP-1 contributes to greater weight loss).
BD: The Auto-Shield Duo (launched in August 2014) was the focus of BD’s small booth tucked in the back left corner of the exhibit hall. Friendly representatives provided a demo of the new pen needle product, while commenting on their excitement at the recent FDA 510(k) clearance of the company’s first-generation insulin infusion set. They acknowledged there has been little innovation in infusion sets over the years – “the weak link in the pump industry.” We are elated to see BD doing its part to change this and believe that Convatec will follow. That said, the question of how to break into this market – and cut into Unomedical’s (Convatec’s) near-monopoly – remains to be answered.
Dexcom: Dexcom’s small, understated booth was lightly trafficked near the entrance of the exhibit hall. The company’s Share receiver with built-in Bluetooth was the major focus of the booth with representative demoing the Share and Follow apps on their phones. While the apps were demoed on iPhones, reps emphasized the software was “coming soon” for Android – certainly by the end of the year but most likely much earlier. Anecdotally, they suggested that uptake of Share has been quick and driven by interest from caregivers looking for solutions to help pediatric patients. Ultimately, there appeared to be a high level of interest among attendees despite the broader endocrinology (including “other endo”) audience. Indeed, one representative shared that when she began working for Dexcom seven years ago, the most common question she received in the exhibit booth was, “What is CGM?” Now, the majority of visitors that approach her exclaim: “We love CGM. We love Dexcom.” Indeed, how far the field has come – but we would urge endos to spread the word since despite the enthusiasm, overall uptake is lower than we would have expected by this point.
Eisai: Eisai had a small pop up booth set up near the back of the exhibit hall, solely focusing on obesity drug Belviq (lorcaserin) in its usual coral/navy blue/white color scheme. The booth’s back wall had three touch screens, which reps used to guide attendees through Belviq’s mechanism of action, clinical data, and patient support.
GSK: GSK occupied one of the larger booths on the exhibit hall floor, but it was tucked away on one side of the hall. As a result, foot traffic was quite low at the time we swung by. Consistent with previous conferences, GSK’s booth was fairly sparse, white, carpeted, and entirely focused on the fairly new once weekly GLP-1 agonist Tanzeum (albiglutide). The screens and displays at the booth stuck fairly closely to the prescribing instructions. Given what GSK has invested in booth space at recent conferences, we are somewhat surprised that the company hasn’t pursued more energetic displays for Tanzeum (for all intents and purposes their only major diabetes product on the market since Avandia’s move to generic status), although the once-weekly GLP-1 agonist class has certainly become more competitive with the entry of new options like Lilly’s Trulicity (dulaglutide).
Insulet: Chocolate Omnipods greeted us at Insulet’s modest booth, tucked away toward the right side of the exhibit hall. We (politely) rebuffed their sugary offers, but took them up on the chance to play with the OmniPod and accompanying PDM. In the company’s classic style, posters of patients tended to display the OmniPod on the tricep, putting a clear emphasis on the product’s small size and wearability. We received confirmation in speaking to reps that the next-gen, Bluetooth-enabled OmniPod PDM will likely be displayed for the first time at ADA 2015. Get ready! The device will be a bit thicker than an iPhone 5 and will feature a color touchscreen and built-in blood glucose meter. We love to see that Insulet is thinking out of the box on this project, since getting Bluetooth, touchscreen, and the Dexcom integration are just a few of the innovations needed to stay ahead of the patient demand curve. No commentary was shared on Insulet’s work in the closed-loop field. C’mon guys, please don’t let the traditional pumps rule this arena …
J&J: As at most diabetes conferences this year, J&J’s booth focused almost entirely on SGLT-2 Invokana (canagliflozin), with only a small corner devoted to the LifeScan division. Interestingly, Invokamet (canagliflozin/metformin) received essentially equal billing to standalone Invokana; we wonder if this reflects a growing popularity of the combination product or is perhaps an attempt to compete with other companies that have SGLT-2 inhibitor/DPP-4 inhibitor fixed-dose combinations (FDCs) on the market or in development – a sales representative did acknowledge that “everyone is interested” in this class. J&J management stated that the company had no plans for such a product as of 3Q14, though we learned recently that Mitsubishi Tanabe is currently conducting a trial investigating co-administration of Invokana with its DPP-4 inhibitor Tenelia (teneligliptin) that will clearly lay the groundwork for a FDC if it works. What else? Maybe J&J should buy Intarcia so it also can promote combo SGLT-2 and GLP-1. In terms of differentiating factors between Invokana and other SGLT-2 inhibitors, a representative noted that Invokana is the only product that has demonstrated superiority vs. active comparators in clinical trials, though she cautioned that there have been no head-to-head studies comparing the three SGLT-2 inhibitors to each other. J&J has clearly benefit from its first-mover advantage…
J&J: LifeScan/Animas: As noted, LifeScan/Animas’ occupied a very small portion of J&J’s overall Diabetes Care real estate. As expected, the Vibe with Dexcom G4 Platinum integration was the major focus of the Animas booth, with attendees encouraged to toggle through the interface and get comfortable with the device. Representatives remarked that early uptake has been quick and were optimistic on the future, despite the coming launch of Tandem’s integrated-CGM platform. They acknowledged that the lack of the meter remote to bolus has been a bit of a disadvantage, especially among women who appreciated the discretion. That said, they were quick to turn the conversation back to the positives of the Vibe, such as recently published results of an accuracy study (Capurro et al.; presented in a poster at ATTD 2015) that show improved dose accuracy, precision, and speed of delivery of the Vibe relative to Tandem’s t:slim and Insulet’s second-gen OmniPod pumps. We are not sure that the results are clinically meaningful. Stepping to the left, we arrived at LifeScan’s small, rectangular counter that displayed the company’s meters, including the OneTouch Verio recently launched in the US in 4Q14. This is the first time we can recall seeing the Verio display at a LifeScan booth; representatives highlighted the color-coding based on in-range results and motivational progress notifications. Both Animas and LifeScan reps were unable to comment on either a launch date for the Finesse (at 1Q15, the Finesse was expected to launch in 2017 at the earliest) or launch metrics on the Verio in the US. We personally are really enjoying the Verio (excellent on-meter branding – we see this more and more since Close Concerns’ insurance company Aetna now charges us $350/month for Abbott strips that go with Kelly’s Omnipod and $50/month for Life Scan strips … “so, yeah, no problem, Aetna, I’m glad to carry around yet another medical device even though this formulary decision means that my safety feature insulin-on-board now doesn’t work on my pump …”).
Lilly: Lilly’s plush carpeted booth was the largest company-sponsored display of the AACE exhibit hall at 50’x50’, located on the front edge of the hall. Given a massive banner for the recently launched first-in-class Glyxambi (empagliflozin/linagliptin) in the conference center lobby, we were a bit surprised to see only a relatively small section of the booth devoted to it. However, representatives at the adjacent Jardiance (empagliflozin) and Tradjenta (linagliptin) sections were eager to discuss the new combination. According to a sales representative, Lilly/BI are seeing Glyxambi prescribed primarily as a third-line option after metformin and a DPP-4 inhibitor or for patients already taking both an SGLT-2 inhibitor and a DPP-4 inhibitor as separate pills. This is somewhat distinct from Lilly management’s suggestion during the company’s 1Q15 update that Glyxambi should appeal primarily to patients on metformin alone and is unlikely to cannibalize Jardiance or Tradjenta sales to a large degree. Lilly’s other new offering, Trulicity (dulaglutide), occupied a more prominent position in the booth, with an entire wall devoted to its impressive clinical data and convenient delivery device – not a surprise given its strong post-launch trajectory. Lilly’s recent marketing push for Humulin R U500 was also evident, though the company appears to have dispensed with the materials we saw at ENDO featuring a woman trapped inside a giant syringe. Dr. Lisa Tannock (University of Kentucky, Lexington, KY) referred to these recent promotional efforts during her talk on insulin resistant patients at a Sanofi breakfast symposium, describing the product as “resurgent.” Indeed, Lilly stated in 2Q14 that Humulin U500 had been a significant driver of Humulin growth; on the flip side, we have also heard complaints from providers about the way Lilly raised the price for Humulin U500 sharply to achieve per-unit price parity with less concentrated formulations.
Medtronic: Medtronic classic light blue signage greeted visitors near the front of the exhibit hall. The small booth allowed attendees to play with the company’s recently launched 530G/Enlite with MiniMed platform; representatives seemed more enthused to talk about the coming MiniMed 640G/Enlite Enhanced CGM system although there was no pre-marketing. This was not on display though there is clearly a lot of excitement here. As a reminder, Medtronic plans to submit a PMA to the FDA for its MiniMed 640G/Enlite Enhanced CGM later this calendar year. Other pipeline items – such as the MiniMed Flex “hybrid pump,” the Enlite 3 sensor, and the type 2 business – were not mentioned in the booth, unsurprisingly since the products themselves are not approved.
Merck: In its typical green and white color scheme, Merck had a decently-sized booth closer to the front of the exhibit hall. Alongside its trusty froyo station, the booth highlighted the company’s Januvia (sitagliptin) franchise, with two boards on Januvia and one on Janumet (sitagliptin/metformin) with clinical data, label information, and images of smiling patients. Unsurprisingly, there was nothing on the FDC product that it has with Pfizer or smart insulin or regular insulin.
Novo Nordisk (diabetes): The company’s centrally located medium-sized diabetes booth followed a familiar path, with a primary focus on Victoza (liraglutide) and Levemir (insulin detemir). The Victoza displays had screens with a plant and root theme, while Levemir displays largely focused on the fairly new FlexTouch pen. There was a large multiscreen display with an animation of the FlexTouch, which is an ergonomic improvement over the previous FlexPen. There were also desks where patients could get some coffee or sign up for the AACE Fun Run (this will be cool!). Consistent with ENDO, the newest offering in Novo Nordisk’s exhibit hall presence was found a few booths away in the Saxenda display (see below).
Novo Nordisk (obesity): The company also had two booths devoted to obesity, one focused on the recently launched Saxenda (liraglutide 3.0 mg) and the second focused on general obesity management. Under a large banner with “Saxenda” displayed in purple text, the Saxenda booth was modestly sized but relatively busy. Most notably, we heard new details (just released today, according to Dr. Apovian) on Saxenda’s savings program under which patients in prescription plans that cover Saxenda can pay no more than $30 per month for up to 12 prescriptions and patients who pay out of pocket can save $200 per month (this information can also be found at www.SaxendaCare.com with a log-in or registration). It will be hard for the smaller companies to compete with this. The booth also gave attendees the opportunity to get a feel for the drug’s purple FlexTouch pen (see our coverage of the approval for more on this), which we learned lasts for six days (each monthly prescription includes five pens). In addition, reps expressed hopes for an improving reimbursement environment and stated that many attendees have asked about the potential overlap between Victoza (liraglutide 1.8 mg) and Saxenda; they have stressed that the distinction will ultimately be based on clinicians’ judgment of what the primary clinical goal is. Novo Nordisk’s second booth, branded “Rethink Obesity” (which offered tea to attendees), focused strictly on general obesity management with reps guiding attendees through education on the basic science behind obesity and providing handouts on resources and tools. While its real estate also remained relatively moderate, reps expressed that the booth has similarly been very active and attracted great interest.
Sanofi: The company had perhaps the best placed booth, right in front of the only main entrance to the exhibit hall. The booth footprint was modest, but all of Sanofi’s US diabetes products were represented. Staring right at you as you entered was a big model of the Toujeo SoloStar pen (a very cool pen) and displays on Toujeo (insulin glargine U300), Sanofi’s new basal insulin option that it hopes will be a successor to market-leading Lantus. The booth seemed to be catching plenty of passers-by due to its placement, and, as a result, a fair number of attendees were receiving introductions to Toujeo’s more stable PK/PD profile and other benefits. A key question in our mind has been whether Sanofi/MannKind’s new inhaled insulin Afrezza might suffer due to Sanofi’s major push on Toujeo. Indeed, and what a missed opportunity in our view, Afrezza was not visible from the front of the booth – similar to the booth layout at ENDO, you had to walk to the inside or around the back to see displays on Afrezza. Reps here framed Afrezza fairly modestly as a “tool” that may be best for some patients rather than a dazzling game-changer – this is probably a wise move to keep expectations at an appropriate level though it certainly is a game-changer for some patients. Booth staff acknowledged that Afrezza is less a product that endos might introduce to every patient and more the type of product that will spread by word of mouth – we’d love to see both. We noticed some updated displays on the lung function test requirements for Afrezza. Very responsibly, the signage made it clear when testing is recommended (before initiation, after six months of use, and annually thereafter) and also mentioned the percentage of patients who smoke or have asthma or COPD to underscore the size of the patient population for whom Afrezza is not the best option. Lantus and Apidra were represented in back corners of the booth and were not receiving much attention since people know what these are.
Tandem: Tandem’s modest booth was located on the right side of the product theater area of the exhibit hall. The company did not have any new marketing or products to share information about – as a reminder, FDA approval/launch of the G4 Platinum integrated t:slim is expected in 2H15 while shipments of the 480-unit t:flex are expected in June.
Vivus: Vivus also had a small, pop-up booth near the back of the hall, which included a medical booth to the side and a few of iPads at the front that featured the Qsymia website, allowing attendees to scroll through the drug’s safety and efficacy information, savings programs, and more. Although Vivus had a small presence in the exhibit hall, it did support a product theater lunch on Qsymia during the day, which focused on the drug’s clinical data and label information along with a focus on best practices for provider/patient communication.
-- by Melissa An, Adam Brown, Varun Iyengar, Emily Regier, Manu Venkat, and Kelly Close