Memorandum
Adocia announced today positive pharmacodynamic and safety topline results for its phase 1 study (n=24) comparing BioChaperone Pramlintide Insulin – fixed-ratio pramlintide (AZ’s amylin analog Symlin) and human insulin – vs. simultaneous injections of pramlintide and human insulin vs. insulin lispro (Lilly’s Humalog) in patients with type 1 diabetes. The study began in April and concluded on schedule.
Per the press release, BC Pramlintide Insulin (containing 7.5U insulin and 45 µg pramlintide) conferred a significant 97% reduction in postprandial blood glucose excursions over the first two hours after eating compared to Lilly’s fast-acting Humalog (mean ΔAUCGIR 0-2h= 4 mg*h/dL, SD=63 for BC Pramlintide Insulin vs. mean ΔAUCGIR 0-2h= 126 mg*h/dL, SD=74 for Humalog; p<0.0001) and comparable postprandial glycemic control to separate injections of Lilly’s Humulin (human insulin) and Symlin (LS-mean ΔAUCGIR 0-2h= 21 mg*h/dL, SD=66).
With respect to safety, BC Pramlintide Insulin was similarly tolerated compared to Symlin/Humulin and Humalog. Four incidences of hypoglycemia occurred in patients taking BC Pramlintide insulin compared to three with Symlin/Humulin and three with Humalog; however, it is worth noting that there were only eight subjects in each study group. There were no GI side-effect warnings with any of the treatments, despite hypoglycemia and GI side-effects being associated with Symlin.
Importantly, this study marks the first clinical demonstration of feasibility for a fixed-ratio co-formulation of pramlintide and human insulin that preserves their known synergistic effect when administered separately – wow! In our view, this emerging class represents a promising advanced approach to postprandial glycemic control. As a reminder, Adocia’s 1Q18 presentation (slide 18) positioned amylin as the “other missing hormone in diabetes.” Unfortunately, even though amylin analogs such as Symlin are effective for postprandial glucose control in both type 1 and type 2 diabetes, this class has failed to gain substantial commercial traction – in large part due to the additional injection burden, hence the value of a coformulation with insulin.
In the press release, it was also noted that the pharmacokinetic profiles of BC Pramlintide Insulin and simultaneous injections of pramlintide and human insulin will be compared in a separate publication. As we understand, preclinical evidence and previous work by Amylin indicating a stronger PK/PD profile with BC Pramlintide Insulin (with human insulin) compared to BC Pramlintide Lispro was a major factor in Adocia’s recent prioritization of the former. To this end, we certainly look forward to seeing the PK data!
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The study also demonstrated similarly slower gastric emptying with BC Pramlintide Insulin and Symlin/Humulin compared to Humalog. In people without diabetes, amylin is naturally co-secreted with insulin and plays an important role in slowing gastric emptying, inhibiting glucagon, and inducing satiety.
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Of note, Adocia has positioned BC Pramlintide Insulin as viable for pump use in a presentation at ADA, emphasizing the combination’s long-term stability in pumps and on the shelf. With this background, we wonder if a pump study is in the near future for BC Pramlintide Insulin as it progresses to phase 2. As far as we know, no future studies for BC Pramlintide Insulin have been announced as of yet.
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According to Adocia’s management, the company’s R&D has received a considerable bump from its partnership with Tonghua Dongbao (THDB). For context, Adocia emphasized in its 2Q18 call that the $50 million up-front payment that it received from the partnership for the development and commercialization of BioChaperone (BC) Lispro and BC Combo in China is enabling R&D acceleration, pointing to the phase 1 study of BC Pramlintide Insulin as an example. Adocia has several other clinical trials slated to begin, including a phase 1/2 trial for BioChaperone Glucagon to start in 3Q18 and a phase 1 trial for BioChaperone Glucagon GLP-1 to start in 1H19.
--by Peter Rentzepis, Martin Kurian, and Kelly Close