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Health 2.0 2018
First published: 03 October 2018
Abstract
Martin J. Kurian, Peter J. Rentzepis, Ann M. Carracher, and Kelly L. Close are of Close Concerns (http://www.closeconcerns.com), a healthcare information company focused exclusively on diabetes and obesity care. Close Concerns publishes Closer Look, a periodical that brings together news and insights in these areas. Each month, the Journal of Diabetes includes this News feature, in which Kurian, Rentzepis, Carracher, and Close review the latest developments relevant to researchers and clinicians.
Health 2.0 2018
The 2018 Health 2.0 conference took place in Santa Clara (CA, USA) on 16-18 September 2018. There, Livongo (Chicago, IL, USA) Chief Product Officer Mr Amar Kendale announced the launch of the company's new cellular-enabled blood pressure cuff, adding more convenient cellular connectivity to Livongo's hypertension program in the US, which launched with Bluetooth in January 2018. This marked the first cellular-enabled blood pressure system. Like the company's cellular-enabled blood glucose monitor, the new device allows for blood pressure monitoring from home and seamless upload to the Cloud, alongside delivery of real-time insights and recommendations (“Health Nudges”) in the Livongo app, both automatically and from coaches. Livongo hopes this cellular-enabled blood pressure system will prevent unnecessary prescriptions for high blood pressure. No pricing information was shared on the standalone hypertension program; list price is US$39 per month before discounts for members already using Livongo for Diabetes. As per Livongo's press release, 81% of the initial cohort with both diabetes and hypertension (n = 276) have reduced their blood pressure using the connected cuff and hypertension program; no cohort size or mean reduction overall were provided.
In addition, Virta Health (San Francisco, CA, USA) Chief Executive Officer Mr Sami Inkinen asserted that continuous remote care could realistically address one-third of US healthcare costs in the future (~US$1 trillion). He based his claim on the promising aspects of continuous remote care: it is affordable, available anywhere, and can produce “transformative outcomes”. On the last of these, Mr Inkinen referred to both published and unpublished data on Virta Health's continuous remote care and ketogenic diet intervention. Regarding unpublished data, Mr Inkinen revealed that new results were just received internally; although no exact numbers or outcomes were divulged, he did share that the company now treats patients in 49 of the 50 states in the US. Previously published 1-year results from Virta demonstrated 60% type 2 diabetes reversal, 1.3% HbA1c reduction (baseline 7.6%), 12% weight loss (approximately 14 kg), and significant improvement in 22 of 26 cardiovascular risk factors at 1 year.1
References
| Company updates | |
|---|---|
| September 5, 2018: | Adocia (Lyon, France) announced positive pharmacodynamic and safety results from a Phase 1 study (n = 24) comparing fixed-ratio pramlintide plus human insulin (BioChaperone Pramlintide Insulin) in patients with type 1 diabetes (T1D) with: (i) simultaneous injections of pramlintide and human insulin; and (ii) insulin lispro. The fixed-ratio pramlintide/human insulin candidate (containing 7.5 U insulin and 45 μg pramlintide) conferred a significant 97% reduction in postprandial blood glucose excursions over the first 2 hours after eating compared with insulin lispro (mean [±SD] change in the area under curve for glucose infusion rate from 0 to 2 hours (ΔAUCGIR 0-2h) = 4 ± 63 mg h dL−1 for fixed-ratio pramlintide and human insulin vs = 126 ± 74 mg h dL−1 for insulin lispro; P < 0.0001). This was comparable to postprandial glycemic control with separate injections of human insulin and pramlintide (least squares mean [±SD] ΔAUCGIR 0-2h = 21 ± 66 mg h dL−1). With regard to safety, fixed-ratio pramlintide/human insulin was tolerated similarly to simultaneous pramlintide and human insulin injections, as well as insulin lispro. Four incidences of hypoglycemia occurred in patients taking fixed-ratio pramlintide/human insulin, compared with three for separate injections and three for insulin lispro. There were no gastrointestinal safety signals with any of the treatments. |
| September 6, 2018: | Zealand Pharma (Glostrup, Denmark) announced an agreement with Royalty Pharma (New York, NY, USA), selling future royalty streams for Sanofi's (Paris, France) Soliqua (insulin glargine/lixisenatide) and Adlyxin (lixisenatide) for US$205 million in cash. Royalty Pharma also gained US$85 million in potential commercial milestones. Zealand will remain eligible for a milestone payment of up to US$15 million from Sanofi in 2020, related to a previously agreed-upon and confidential settlement. |
| September 7, 2018: | Johnson & Johnson's (New Brunswick, NJ, USA) sodium-glucose cotransporter 2 (SGLT2) inhibitor Invokana (canagliflozin) received a cardiovascular (CV) indication in the European Union. The European Commission approved an update to Invokana's indication statement and the addition of data from the CANagliflozin cardioVascular Assessment Study (CANVAS) trial2 to the drug's product information. The label will now include information on Invokana's effects on major adverse cardiovascular events (MACE) in patients with type 2 diabetes (T2D) who have CV disease or are at high CV risk. The change also applies to Vokanamet, the fixed-dose combination of canagliflozin with metformin. |
| September 10, 2018: | Arecor (Saffron Walden, UK) recently announced securement of an additional £6 million (~US$7.8 million) to advance its preclinical diabetes portfolio into in-human trials. The pipeline includes an ultra-concentrated U1000 rapid-acting insulin, an ultra-rapid-acting prandial insulin, and a liquid-stable glucagon. According to the announcement, Arecor will bring its current portfolio into clinical development alone, but will look to partner candidates for late-stage clinical development and global commercialization. |
| September 12, 2018: | MannKind (Westlake Village, CA, USA) announced that full results from the Study Comparing Prandial Insulin Aspart vs Technosphere Insulin in Patients With Type 1 Diabetes on Multiple Daily Injections (STAT) have been published in Diabetes Technology & Therapeutics.3 The STAT trial (n = 60) compared MannKind's ultra-rapid-acting inhalable Technosphere insulin Afrezza to Novo Nordisk's (Bagsværd, Denmark) insulin aspart (NovoLog); Dexcom's (San Diego, CA, USA) G5 continuous glucose monitor was used over the 4-week study. A significant (P < 0.05) 2.1-h increase in time-in-range was seen in patients who complied with their Technosphere insulin regimen vs patients on insulin aspart. The publication indicates that only those who adhered to the Technosphere insulin regimen experienced a significant decrease in postprandial excursions compared with insulin aspart, although no exact value was given. Those who adhered to the Technosphere insulin regimen also spent significantly less time per day in hyperglycemia (>10 mmol/L) than patients on insulin aspart (8.2 vs 9.8 h/d; P < 0.05). A significant reduction in time spent in hypoglycemia <3.3 mmol/L (P = 0.02) and < 2.8 mmol/L (P = 0.04) was found when comparing the combined Technosphere insulin groups (adherent and non-adherent) to insulin aspart, when adjusting for study week, HbA1c at screening, and other variables. |
| September 17, 2018: | The US Food and Drug Administration (FDA) announced that it will hold an Advisory Committee meeting on 24-25 October 2018, to discuss the future of CV outcomes trials (CVOTs) for new glucose-lowering therapies, as well as to review what has been learned over the past decade. |
| September 18, 2018: | Novo Nordisk announced that it will lay off approximately 400 research and development employees in Denmark and China as part of a change to its drug identification and development strategy. As part of this restructuring, Novo Nordisk will establish four “Transformational Research Units” later in 2018 to pursue new platform technologies and treatment modalities. This will include investing in machine learning and artificial intelligence as a means to more quickly and efficiently select molecules for development. |
| September 17, 2018: | ViaCyte (San Diego, CA, USA) announced a collaboration with CRISPR Therapeutics (Zug, Switzerland) to develop an immune-evasive stem cell line that would enable a β-cell-replacement therapy for T1D and insulin-requiring patients with T2D. ViaCyte and CRISPR Therapeutics will partner for both development and commercialization of an allogeneic, stem cell-derived product. According to the agreement, ViaCyte will receive US$15 million and has the right to receive another US$10 million early next year in the form of a note. Should a clinical candidate be identified, CRISPR will pay for 60% of development costs and the companies will share profits. |
| September 17, 2018: | Oramed (Jerusalem, Israel) announced that FDA has approved an investigational new drug (IND) application for oral glucagon-like peptide-1 (GLP-1) agonist ORMD-0901 (oral exenatide). The company plans to initiate a Phase 1 safety and pharmacokinetic study (n = 15) in the third quarter of 2018, comparing ORMD-0901 to AstraZeneca's (Cambridge, UK) Byetta (twice-daily injectable exenatide) and placebo. A broader Phase 2 study is slated to begin in the US in 2019. |
| September 18, 2018: | Zealand announced positive results for the pivotal Phase 3 trial (n = 168 adults with T1D) of the HypoPal (dasiglucagon) rescue pen (completed May 2018). Dasiglucagon was compared to placebo and Novo Nordisk's GlucaGen (glucagon reconstitution kit) when administered as a single-dose hypoglycemia rescue treatment. On the primary endpoint of time to plasma glucose recovery (defined as first increase in plasma glucose of ≥1.1 mmol/L from baseline without administration of rescue intravenous glucose), median time to blood glucose recovery with dasiglucagon (n = 82) was 10 minutes (95% confidence interval [CI] 10-10 minutes). This was significantly (P < 0.001) faster than placebo (n = 43; mean time 40 minutes, 95% CI 30-40 minutes) and numerically faster than the reconstitution kit (n = 43; 12 minutes, 95% CI 10-12 minutes). In addition, 99% of subjects recovered from insulin-induced hypoglycemia within 15 minutes with dasiglucagon, compared with 95% of subjects with the reconstitution kit and 2% of subjects with placebo (P < 0.001). Dasiglucagon did not raise any independent safety concerns, and nausea and vomiting were comparable between the dasiglucagon and reconstitution kit groups (55% vs 53%, respectively, for nausea; 23% vs 19%, respectively, for vomiting). |
| September 18, 2018: | Viking Therapeutics (San Diego, CA, USA) announced positive topline results from a Phase 2 study (n = 80) of the oral liver-selective thyroid receptor antagonist VK2809 in non-alcoholic fatty liver disease (NAFLD)/hypercholesterolemia, on schedule with anticipated timing. On the primary endpoint of change in low-density lipoprotein cholesterol (LDL-C), participants receiving VK2809 saw a significant improvement of ≥20% reduction compared with placebo at 12 weeks (no numbers or measures of significance were given). On the key secondary endpoint of reduction in liver fat content, VK2809 also gave significant reductions compared with placebo at 12 weeks, as measured by magnetic resonance imaging. Among those receiving VK2809, 83% experienced a ≥ 30% reduction in liver fat content, compared with 18% with placebo (P < 0.01 for comparison). |
| September 20, 2018: | Novo Nordisk announced positive topline results from the Safety and Efficacy of Oral Semaglutide vs Dulaglutide Both in Combination With One OAD (Oral Antidiabetic Drug) in Japanese Subjects With Type 2 Diabetes (PIONEER 10; n = 458) trial. The PIONEER 10 trial randomized patients already on one oral diabetes drug to one of three doses of oral semaglutide (3, 7, and 14 mg) or to dulaglutide 0.75 mg (randomized 2: 2: 2: 1, respectively). This is the lower dose of Eli Lilly's (Indianapolis, IN, USA) Trulicity, which is the only dose approved by Japan's Pharmaceutical and Medical Devices Agency. According to the intention-to-treat analysis, 14 mg oral semaglutide gave significantly greater reductions in HbA1c and body weight compared with dulaglutide at 52 weeks. In the on-treatment analysis, 14 mg oral semaglutide gave a 1.8% drop in HbA1c compared with 1.3% with dulaglutide at 52 weeks, and from a baseline HbA1c of 8.3%; this difference was significant. In addition, 3 and 7 mg oral semaglutide resulted in 0.7% and 1.4% drops in HbA1c, respectively; no statistical comparisons were offered. Body weight fell by 1.9 kg with 14 mg oral semaglutide after 52 weeks, also in the on-treatment analysis; this was a significant improvement over the 1.1 kg weight gain in the dulaglutide group. In the group receiving 3 mg oral semaglutide, subjects gained 0.1 kg, whereas those receiving 7 mg oral semaglutide lost 1.0 kg, on average, at 52 weeks. Among those receiving 14 mg oral semaglutide, 58% achieved an HbA1c <6.5% in the on-treatment analysis. This metric was achieved by 21% of those on 3 mg oral semaglutide, 43% on 7 mg oral semaglutide, and 41% on dulaglutide 0.75 mg. |
| September 24, 2018: | Amarin (Dublin, Ireland) released positive topline results from A Study of AMR101 to Evaluate Its Ability to Reduce Cardiovascular Events in High Risk Patients With Hypertriglyceridemia and on Statin (REDUCE-IT; n = 8179). The REDUCE-IT study investigated the use of Vascepa (icosapent ethyl, a pharmaceutical-grade fish oil supplement) in statin-treated adults with LDL-C controlled to 2.3-5.5 mmol/L and persistent elevated triglycerides of 8.3-27.7 mmol/L, as well as elevated CV risk. This prospective, multicenter randomized double-blind parallel-group study found that 4 g/d Vascepa gave a significant “~25%” relative risk reduction in M-ACE (cardiovascular death, nonfatal myocardial infarction, non-fatal stroke, coronary revascularization, unstable angina requiring hospitalization) compared with placebo. The study included both primary prevention (~30% of the total cohort; defined as T2D, age > 50 years, and at least one CV risk factor) and secondary prevention (~70% of the total cohort; defined as age > 45 years and established CV disease) groups. Vascepa was well tolerated, and the proportion of patients experiencing adverse events and serious adverse events in REDUCE-IT were similar between the study groups. |
| September 24, 2018: | AstraZeneca announced topline results from the Multicenter Trial to Evaluate the Effect of Dapagliflozin on the Incidence of Cardiovascular Events (DECLARE-TIMI58) for the SGLT2 inhibitor Farxiga (dapagliflozin). Dapagliflozin achieved superiority over placebo on one of the study's two coprimary endpoints, a composite of hospitalization for heart failure and CV death, making it the first SGLT2 inhibitor to demonstrate heart failure benefit as a primary endpoint result. On the other coprimary endpoint, three-point MACE (CV death, heart attack, and stroke), Farxiga exhibited non-inferiority but not superiority over placebo, although the company's press release notes that results trended in favor of Farxiga. No hazard ratios (HRs) or P-values were provided in the press release. |
| September 25, 2018: | AstraZeneca announced a positive opinion from the European Union's Committee for Medicinal Products for Human Use (CHMP) in response to the company's request that data from the Exenatide Study of Cardiovascular Event Lowering Trial (EXSCEL)4 be added to the European label for the GLP-1 agonist Bydureon (exenatide once-weekly). Bydureon's European Union label will now include the primary endpoint from EXSCEL, which missed the statistical threshold for superiority vs placebo on three-point MACE (non-fatal heart attack, non-fatal stroke, CV death) with an HR of 0.91 (95% CI 0.83-1.00). Results trended in favor of Bydureon, which was associated with 839 CV events (11.4% of participants), compared with 905 (12.2%) in the placebo arm. The label will also gain data for the secondary endpoint of all-cause mortality, for which Bydureon demonstrated a statistically significant 14% reduction compared with placebo (HR 0.86; 95% CI 0.77-0.97; P = 0.016). |
