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Disease Analysis: Type 1 Diabetes

  • ID: 4997158
  • Report
  • May 2021
  • Region: Global
  • 87 Pages
  • Pharma Intelligence
Disease Definition

Diabetes mellitus is a group of chronic endocrine disorders characterized by hyperglycemia due to insufficient levels of insulin, a hormone responsible for regulating blood sugar. Symptoms include excessive excretion of urine (polyuria), thirst (polydipsia), constant hunger, weight loss, vision changes, and fatigue. According to the World Health Organization (WHO), approximately 8.5% of adults had diabetes in 2014. Type 1 diabetes accounts for around 5-10% of the total diabetic population. The majority of cases of type 1 diabetes may be classified as type 1a, an autoimmune disease characterized by the destruction of pancreatic beta cells, with a minority of cases making up type 1b, which is described as idiopathic diabetes mellitus.

Latest Key Takeaways

  • Despite newer products with improved PK/PD profiles, the type 1 diabetes treatment market has been gradually declining in value, driven by declines in the US, and factors contributing to this are expected to continue, including net pricing pressures following the launches of biosimilars, saturation with multiple maturing insulins, and limited or uncertain prospects of non-insulin therapies. That said, if very early-stage transformative technologies succeed, such as glucose-responsive insulins, they could recast the market, but there is a lack of good clinical data on these to date.
  • In the basal insulin segment, with the advent of biosimilars/follow-on copies to segment-leader Sanofi’s Lantus, Sanofi and Novo Nordisk have introduced next-generation, longer-acting products; however, due to continued price pressures, especially in the US, these have not prevented overall sales declines. Sanofi’s longer-acting Toujeo does have some signals for a hypoglycemia benefit over Lantus, but not as much in type 1 diabetes as in type 2, and does allow some patients who require twice-daily Lantus to inject once-daily. However, KOLs interviewed by the publisher suggest that the advantages are somewhat limited, and with modest sales in the US due to competition with Basaglar, a follow-on copy of Lantus, Toujeo has not prevented a 60% drop in combined US sales with Lantus over the past few years, leading to a 34% drop worldwide, despite some combined stability ex-US. Prescriptions of Lantus and Toujeo have stabilized somewhat over the past few years in the US, but the introduction of another follow-on copy, Semglee, in 2020 could introduce further pricing pressures. Semglee has also been filed for interchangeability.
  • Novo Nordisk’s basal analog Levemir, which requires twice-daily dosing in many type 1 patients, has generally lost share to its successor product Tresiba due to the company’s promotion of Tresiba’s longer-acting duration of 42+ hours and its flexible dosing window (it can be administered at different times each day), which offer improved convenience for patients. Tresiba also has hypoglycemia benefits over Lantus, with a reduction in severe hypoglycemia in a large outcomes study, albeit in type 2 diabetes, with data appearing on its US label. Nevertheless, while Tresiba appears more differentiated than Toujeo, it has been difficult to discern whether there are substantial differences in other clinical benefits between the two, because each sponsor has conducted head-to-head PK/PD and longer-term hypoglycemia studies, but those studies have either shown equivalence or an advantage for the sponsor’s drug (the larger studies have been in type 2). While Tresiba had helped increase combined overall usage of the Novo Nordisk franchises, more recently it appears to be just stabilizing combined usage (with some combined volume loss in major developed markets), and all this has come at the expense of increasing rebates in the US, so in recent years, despite combined sales growth ex-US, worldwide sales have declined 25%. Tresiba’s volume share growth in the US also appeared to stall in 2020, with a notable drop in sales due to net price decreases, so it is somewhat unclear how much more it can capitalize there on its advantageous profile.
  • Payers are severely restricting the use of specific insulin brands in the US. While list prices are increasing, rebates are also rising, particularly in the past few years. Interviewed endocrinologists emphasized the impact of pricing on prescribing trends, as formulary changes in the US lead to regular switching among patients.
  • Dynamics are somewhat different in the fast-acting/bolus segment of the market, due to more exclusive contracting in the US which has made it more difficult for biosimilar/follow-on copies to gain a foothold, though they still contribute to pricing pressure. It has also been more difficult to differentiate next-generation, faster-acting products.
  • The segment leaders to date have been Eli Lilly’s Humalog and Novo Nordisk’s NovoLog. Interviewed KOLs believe there are no definitive clinical differentiators between the two in a real-world setting. Overall worldwide sales of NovoLog appear modestly higher than Humalog, though there are differences within particular geographic regions (and there can be some impact from exchange rates). However, largely due to price pressures, Humalog and NovoLog sales have declined in the US over the past five years, and sales gains for both outside the US have not been enough to prevent modest declines overall. While the introduction of Sanofi’s biosimilar/follow-on copy to Humalog, Admelog, has only led to modest sales, primarily in the Medicaid market in the US, it did prompt the other manufacturers to launch “authorized follow-ons/generics” with 50% lower list prices in 2019-20, in order to increase competitiveness in plans such as US Medicare Part D, where patients can end up having to pay a portion of a drug’s gross cost. Viatris and Sanofi are pursuing US approval as interchangeable insulins for their biosimilars of NovoLog, so it will be interesting to see whether that makes a difference.
  • Novo Nordisk’s faster-acting Fiasp can be injected at the start of a meal or within 20 minutes after, rather than immediately before or soon after for NovoLog. Nevertheless, clinicians have been underwhelmed as its faster onset of action has not provided a substantial therapeutic benefit, so uptake has been limited so far. Eli Lilly’s faster-acting Lyumjev launched in mid-2020 in major markets, and while it can also be injected within 20 minutes after a meal, its data are somewhat weaker than Fiasp’s, and expectations are limited.
  • Use of continuous subcutaneous insulin infusion (CSII), or insulin pumps, has been increasing, with penetration in the US in a large minority of type 1 patients. The currently available most advanced systems are still hybrid closed-loop, meaning that while they adjust basal insulin frequently in response to a continuous glucose monitor (CGM) - or in some cases, also give an automatic bolus dose - they do not take over glucose control completely, and patients need to still input information for mealtime boluses. The latter may be a difficult issue to overcome, given time lags between interstitial fluid CGM measurements and blood glucose measures, though companies are also working on incorporating glucagon and using artificial intelligence to better adapt insulin delivery to each patient’s fluctuating glucose trends.
  • Pipeline product teplizumab has shown promising potential to prevent or delay the onset of type 1 diabetes, as Phase II data have demonstrated that a single course of the drug significantly delayed disease onset in at-risk patients by a median of 2.7 years. However, while a rolling BLA was completed in late 2020, the FDA has said there are issues with the comparability of drug product intended for commercialization versus that used in the pivotal trial, and it is not yet clear how that will be resolved. In addition, repeat dosing has not been tested, and patients are still being followed. Hence, it will face the challenge of appropriate pricing to reflect the market value of delaying or preventing diabetes while ensuring that a high upfront cost does not prevent reimbursement or lead to overbearing prior authorization. Another challenge is the lack of existing screening programs to detect patients who are at risk for type 1 diabetes, which could limit the drug’s target population (at least initially). Teplizumab’s commercial success will therefore require healthcare services, physicians, and industry to collaborate on creating and integrating accessible screening programs into different health services globally.
  • SGLT-2 inhibitors may offer benefits to type 1 diabetes patients beyond improved glycemic control (such as blood pressure reduction, weight loss, and cardiorenal benefits), but the FDA has now rejected all three members of the class that have been filed for regulatory approval, and Farxiga and Jardiance are no longer pursuing US approval, leaving Zynquista, which has had a couple of appeals denied. The publisher’s base case is that the class will not gain FDA approval for type 1 diabetes without additional studies to further investigate the risk of diabetic ketoacidosis, the durability of glycemic benefits, and the effectiveness of proposed risk-management strategies, which at this point appears unlikely.
  • The publisher estimates that in 2018, there were approximately 46.6 million prevalent cases of type 1 diabetes in adults aged 20 years and over worldwide, and forecasts that number to increase to 51.8 million prevalent cases by 2027.
  • The publisher estimates that in children and adolescents aged below 20 years, there were approximately 1.08 million prevalent cases of type 1 diabetes worldwide in 2018, which are expected to increase to 1.12 million prevalent cases by 2027.
  • The overall likelihood of approval of a Phase I type 1 diabetes asset is 12.8%, and the average probability a drug advances from Phase III is 76%. Type 1 diabetes drugs, on average, take 9.6 years from Phase I to approval, compared to 9.7 years in the overall endocrine space.
Note: Product cover images may vary from those shown
OVERVIEW
  • Latest key takeaways

DISEASE BACKGROUND
  • Disease definition
  • Patient segmentation
  • Diagnosis

TREATMENT
  • Daily insulin replacement therapy is required to prevent hyperglycemia

EPIDEMIOLOGY
  • Prevalence methodology in adults (20–85+ years)
  • Prevalence methodology in children and adolescents (0–19 years)

MARKETED DRUGS

PIPELINE DRUGS

KEY REGULATORY EVENTS
  • Breakthrough Therapy Designations At US FDA Stay Sluggish In 2021
  • CellTrans’ Donislecel Gets US FDA Panel Nod For Small Group Of Type 1 Diabetics
  • FDA Perturbed By Provention’s Teplizumab Type 1 Diabetes Drug
  • Zealand Set To Take On Lilly After Zegalogue US Approval
  • Sotagliflozin Hail Mary? Lexicon Seeks Opportunity For Formal Hearing On FDA Intent To Deny Approval
  • Biocon And Viatris Scoop EU Insulin Aspart Approval
  • Amphastar Has First US Glucagon Rival
  • Viatris’ Insulin Aspart Endorsed By EMA
  • Xeris Picks Up European Nod
  • Teplizumab Speeds Toward Delay Of Type 1 Diabetes Indication
  • FDA Approves Medtronic’s Bluetooth-Enabled Insulin Pump For Children Ages 2 To 6
  • Excalibur To Test AZ Compound In Diabetics With COVID-19
  • Sanofi Has EU Insulin Aspart Biosimilar Approval
  • Lilly Lyumjev Took BLA Path To Approval
  • ADA 2020: Tandem Wins FDA Nod For T:Slim Pump Technology In Children; Positive Feedback on Studies
  • Mylan And Biocon’s Semglee Insulin Glargine Approved In US
  • Sanofi’s Insulin Aspart Biosimilar Gets European Nod
  • Provention Bio Teplizumab On Track To Complete BLA By Year-End

PROBABILITY OF SUCCESS

LICENSING AND ASSET ACQUISITION DEALS
  • Medtronic Addresses Diabetes Care Disparities With New Equity Initiatives
  • Biolojic To Use Computational Platform For Lilly, Nektar
  • Biocon And International Diabetes Federation Promote Insulin Access
  • Novo Nordisk Accesses Diabetes Delivery Tech From Procyon
  • Philips Extends Leadership In Patient Monitoring By Buying BioTelemetry For $2.8Bn
  • Abbott Becomes First Anchor Sponsor For American Diabetes Association Health Equity Now Initiative
  • Exec Chat: How Glooko Plans To Ride Digital Health Care Wave To Profitability
  • Medtronic Adds Smart Insulin Pen By Acquiring Companion Medical
  • Rise Of Digital Health: Teladoc Acquires Livongo In $18.5Bn Deal, Creating Virtual Care Giant
  • Medtronic/Tandem Patent Agreement Paves Way For Diabetes Product Development
  • Blackstone Invests $337M In Medtronic’s Diabetes R&D

CLINICAL TRIAL LANDSCAPE
  • Sponsors by status
  • Sponsors by phase
  • Recent events

DRUG ASSESSMENT MODEL
  • Long-acting insulins
  • Rapid-acting insulins
  • Non-insulin treatments

MARKET DYNAMICS

FUTURE TRENDS
  • Questionable clinical benefit and pricing pressure from biosimilars will slow uptake of next-generation products
  • Pricing pressure in the US diabetes market will continue to impact rebates or shift prescribing trends towards more affordable insulins
  • Teplizumab uptake will be dependent on overcoming pricing and reimbursement issues, along with the introduction of screening programs to identify at-risk patients
  • SGLT-2 inhibitors are expected to have slow uptake in the EU and Japan due to narrow target populations, DKA risk, and minor glycemic benefits

CONSENSUS FORECASTS

RECENT EVENTS AND ANALYST OPINION
  • Donislecel for Diabetes Mellitus, Type I (April 15, 2021)
  • Donislecel for Diabetes Mellitus, Type I (April 13, 2021)
  • TTP399 for Diabetes Mellitus, Type I (February 23, 2021)
  • Diamyd for Diabetes Mellitus, Type I (September 14, 2020)
  • ProTrans for Diabetes Mellitus, Type I (September 8, 2020)
  • XP-3924 for Diabetes Mellitus, Type I (June 18, 2020)
  • NN9828 for Diabetes Mellitus, Type I (June 15, 2020)
  • Teplizumab for Diabetes Mellitus, Type I (June 15, 2020)
  • AT247 for Diabetes Mellitus, Type I (June 14, 2020)
  • TTP399 for Diabetes Mellitus, Type I (June 13, 2020)

KEY UPCOMING EVENTS

KEY OPINION LEADER INSIGHTS

UNMET NEEDS
  • Smart insulins or other novel therapies that reduce the risk of hypoglycemia
  • Continued improvement in options for insulin administration and automated blood glucose control
  • Prevention of type 1 diabetes

BIBLIOGRAPHY

APPENDIX

LIST OF FIGURES
Figure 1: Guideline diagnostic criteria for type 1 diabetes
Figure 2: Recommended steps following type 1 diabetes treatment initiation
Figure 3: Trends in prevalent cases of type 1 diabetes in adults (20–85+ years), 2018–27
Figure 4: Trends in prevalent cases of type 1 diabetes in children and adolescents (0–19 years), 2018–27
Figure 5: Overview of pipeline drugs for type 1 diabetes in the US
Figure 6: Pipeline drugs for type 1 diabetes, by company
Figure 7: Pipeline drugs for type 1 diabetes, by drug type
Figure 8: Pipeline drugs for type 1 diabetes, by classification
Figure 9: Probability of success in the type 1 diabetes pipeline
Figure 10: Clinical trials in type 1 diabetes
Figure 11: Top 10 drugs for clinical trials in type 1 diabetes
Figure 12: Top 10 companies for clinical trials in type 1 diabetes
Figure 13: Trial locations in type 1 diabetes
Figure 14: Type 1 diabetes trials status
Figure 15: Type 1 diabetes trials sponsors, by phase
Figure 16: The publisher’s drug assessment summary for type 1 diabetes
Figure 17: Market dynamics in type 1 diabetes
Figure 18: Future trends in type 1 diabetes
Figure 19: TTP399 for Diabetes Mellitus, Type I (February 23, 2021): Phase Ib/II - SimpliciT1
Figure 20: Diamyd for Diabetes Mellitus, Type I (September 14, 2020): Phase IIb - DIAGNODE-2
Figure 21: ProTrans for Diabetes Mellitus, Type I (September 8, 2020): Phase I/II - ProTrans- 1/2 (Dose Escalation)
Figure 22: XP-3924 for Diabetes Mellitus, Type I (June 18, 2020): Phase II - PK/PD Study
Figure 23: NN9828 for Diabetes Mellitus, Type I (June 15, 2020): Phase II - Proof-of-Principle
Figure 24: Teplizumab for Diabetes Mellitus, Type I (June 15, 2020): Phase II - At-Risk (NIDDK)
Figure 25: AT247 for Diabetes Mellitus, Type I (June 14, 2020): Phase I - ARE-247-101 (Austria)
Figure 26: TTP399 for Diabetes Mellitus, Type I (June 13, 2020): Phase Ib/II - Simplici-T1
Figure 27: Key upcoming events in type 1 diabetes

LIST OF TABLES
Table 1: Prevalent cases of type 1 diabetes in adults (20–85+ years), 2018–27
Table 2: Prevalent cases of type 1 diabetes in children and adolescents (0–19 years), 2018–27
Table 3: Marketed drugs for type 1 diabetes
Table 4: Pipeline drugs for type 1 diabetes in the US
Table 5: Historical global sales, by drug ($m), 2016–20
Table 6: Forecasted global sales, by drug ($m), 2021–25
Table 7: Donislecel for Diabetes Mellitus, Type I (April 15, 2021)
Table 8: Donislecel for Diabetes Mellitus, Type I (April 13, 2021)
Table 9: TTP399 for Diabetes Mellitus, Type I (February 23, 2021)
Table 10: Diamyd for Diabetes Mellitus, Type I (September 14, 2020)
Table 11: ProTrans for Diabetes Mellitus, Type I (September 8, 2020)
Table 12: XP-3924 for Diabetes Mellitus, Type I (June 18, 2020)
Table 13: NN9828 for Diabetes Mellitus, Type I (June 15, 2020)
Table 14: Teplizumab for Diabetes Mellitus, Type I (June 15, 2020)
Table 15: AT247 for Diabetes Mellitus, Type I (June 14, 2020)
Table 16: TTP399 for Diabetes Mellitus, Type I (June 13, 2020)
Note: Product cover images may vary from those shown