Disease Analysis: Type 1 Diabetes

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 the presence of multiple well-established products, the type 1 diabetes market is expected to see limited growth over the next decade. Future growth opportunities in the type 1 diabetes market are expected to be limited by its saturation with multiple maturing insulins, pricing pressures following the launches of biosimilars, and the expected failure of sodium-glucose cotransporter-2 (SGLT-2) inhibitors to gain approval in the lucrative US market.
• Datamonitor Healthcare expects patients will continue to switch from Novo Nordisk’s Levemir to its successor product Tresiba due to the company’s promotion of Tresiba’s longer duration of blood sugar control compared to Levemir. Likewise, Sanofi is pursuing a comparable commercial strategy to Novo Nordisk by promoting its next-generation insulin glargine product Toujeo over Lantus, as Lantus continues to lose patient share to the more affordable biosimilar Basaglar. However, key opinion leaders interviewed by Datamonitor Healthcare suggest that physicians are unconvinced that Toujeo possesses tangible benefits over biosimilar insulin glargine to justify its higher price.
• Payers are severely restricting the use of specific insulin brands in the US. As the list price of insulins continues to increase, cost is becoming a strong determining factor for the choice of insulin treatment. Interviewed endocrinologists emphasized the impact of pricing on prescribing trends, as price fluctuations in the US lead to regular switching among patients.
• Tresiba is forecasted to see the greatest uptake of all the long-acting insulin therapies in type 1 diabetes. Its long-acting duration of 42+ hours and its flexible dosing window (it can be administered at different times each day) offer improved convenience for patients, along with strong glycated hemoglobin (HbA1c) reductions. In addition, favorable pricing compared to Lantus and Toujeo within the US market is expected to drive growth of Novo Nordisk’s market share.
• The maturation of multiple short-acting insulin products has resulted in companies promoting switching to successor products with extended patent protection to maintain their diabetes revenues. Novo Nordisk’s NovoLog will be facing biosimilar competition from Sanofi’s SAR341402, therefore Novo Nordisk is actively encouraging patients to switch to NovoLog’s successor ultra-rapid product Fiasp, which is positioned as having a faster onset of activity than NovoLog. Similarly, Eli Lilly has developed a faster-acting version of Humalog, ultra-rapid lispro, which is currently in preregistration in the US.
• Increasing out-of-pocket costs for patients and competition from Sanofi’s Admelog (a biosimilar of Humalog) have resulted in developers of branded products launching authorized generics in order to increase competitiveness in US government-insured patients, who must make co-payments based on a percentage of a drug’s list price. In May 2019, Eli Lilly launched an authorized generic of Humalog at 50% of the list price of branded Humalog in hopes of maintaining government-insured patient share. This was followed in January 2020 by Novo Nordisk’s launch of an authorized generic version of NovoLog, also at a 50% discount to the branded product.
• 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 two years. Provention Bio began a rolling Biologics License Application (BLA) submission for the prevention or delay of type 1 diabetes in April 2020, and expects to complete the BLA by the end of 2020. The review process will be fast tracked due to Breakthrough Therapy designation granted by the US Food and Drug Administration (FDA), allowing for possible approval in mid-2021. However, if approved, teplizumab is likely to face two challenges when attempting to enter the market, the first of which is appropriately pricing the product to reflect the market value of delaying or preventing diabetes while ensuring that a high upfront cost does not prevent reimbursement. Indeed, achieving widespread reimbursement will be particularly challenging given the lack of a currently approved comparator and the fact that the mean duration of any delay in the onset of diabetes may not be known at the time of approval. The second challenge is the lack of existing screening programs to detect patients that are at risk for type 1 diabetes, which could severely 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 (namely blood pressure reduction and weight loss), but the FDA has now rejected all three members of the class that had been filed for regulatory approval (Farxiga, Jardiance, and Zynquista). Our 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 (DKA), the durability of glycemic benefits, and the effectiveness of proposed risk-management strategies. Thus far, none of the companies have publicly announced any intention to conduct such studies. In fact, Eli Lilly decided to discontinue further development of Jardiance for type 1 diabetes in April 2020, and AstraZeneca has not provided any further updates on Farxiga’s supplemental New Drug Application (sNDA) since its initial rejection by the FDA in July 2019, thus we expect that the company will also abandon US development. Lexicon has expressed its reluctance to conduct additional trials for Zynquista and has instead unsuccessfully appealed twice to the FDA to overturn its initial rejection. While Lexicon claimed it still has options available for Zynquista’s US approval in its Q1 2020 earnings call, we believe that the FDA is highly unlikely to approve the drug in the absence of new trial data.
• Datamonitor Healthcare 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.
• Datamonitor Healthcare 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 14.8%, and the average probability a drug advances from Phase III is 75%. Type 1 diabetes drugs, on average, take 9.1 years from Phase I to approval, compared to 9.4 years in the overall endocrine space.