Achieving glycemic control and managing hypoglycemia are two of the largest unmet needs in the treatment of Type 1 Diabetes (T1D), according to GlobalData. The leading data and analytics company notes that there is great potential for coformulations of Symlin (pramlintide) and insulin, which may together address many of the unmet needs that remain with insulin-only treatments.

Samisha Khangaonkar, Pharma Analyst at GlobalData, comments: “An injectable form of human amylin, pramlintide has long been the unfavorable adjunct therapeutic for T1D in the US. It is not very popular among T1D patients and there are some serious limitations to the drug’s use due to increased rates of hypoglycemia. However, while Symlin’s role as an adjunct was disappointing to both patients and key opinion leaders (KOLs) alike, its potential for coformulation with insulin is showing promise, following its patent expiry in 2019. Such coformulations – particularly in combination with insulin pumps and continuous glucose monitors – could disrupt the current insulin standards.

“Results presented at the American Diabetes Association (ADA) demonstrated the benefit of the combination of both hormones in addressing postprandial changes in blood glucose, which is difficult to manage with any of the currently marketed insulins alone.”

GlobalData has found that over 90% of T1D patients in the US still experience recorded hypoglycemia, with over 27% experiencing severe hypoglycemic events, 54% with nocturnal hypoglycemia, and over 21% with hypoglycemia unawareness. Globally 47% of T1D patients are overweight or obese, and only 20–30% of T1D patients meet their glycemic targets.

Khangaonkar continues: “Insulin pumps and continuous glucose monitors are helping to an extent, but many patients still require additional help.”

Three companies are looking into coformulation with pramlintide: Adocia, Xeris and Arecor. Previously, AstraZeneca was investigating the coformulation of pramlintide with a human insulin, but it has since discontinued research in the space.

Khangaonkar adds: “Adocia’s insulin co-formulation pipeline is the most robust, with three different coformulations in development. Adocia presented data from part two of the Phase Ib trial of M1Pram (ADO09, human insulin + pramlintide) at ADA. Further, in late June, the company announced it had dosed its first patient in a Phase I trial investigating BioChaperone LisPram (insulin lispro + pramlintide) for insulin pump delivery in comparison with Humalog. A coformulation of insulin aspart and pramlintide is also in early development.

“Meanwhile, while Xeris’ phase II results are promising, Xeris will need to use an insulin analog as the active comparator to demonstrate a benefit, as human insulins are no longer actively prescribed. In addition, time-in-range will be a critical endpoint to include as more patients adopt continuous glucose monitoring.

“Arecor’s AT299 (insulin + pramlintide), is still preclinical.”

Some KOLs have expressed pushback against the use of pramlintide due to their experiences prescribing the original formulation and the increased hypoglycemia and gastrointestinal symptoms. However, others have pointed out that these novel formulations have different pharmacokinetics and that coformulation seems to provide greater benefits and no hypoglycemia, despite the continuation of some gastrointestinal symptoms.

Khangaonkar says: “Amylin inhibits glucagon secretion, delays gastric emptying, and acts as a satiety agent in addition to its impact on blood glucose. With some interviewed KOLs calling pramlintide the ‘new glucagon,’ there is great potential for these therapies as they reduce the number of therapeutics, injections needed, and units of insulin per day—all of which make the daily management of T1D easier on the patient.”

Innovation in the insulin space has been relatively consistent over the last 20 years. Human insulins were replaced by insulin analogs, and now second-generation insulin analogs are becoming established in the market. However, the relative impact of these insulins on a patient’s quality of life is often not significant enough to warrant the premium pricing.