Adocia’s BioChaperone Lispro shows faster offset vs. Novo Nordisk’s Fiasp in head-to-head PK/PD study – December 18, 2017

Adocia just released topline data from the first head-to-head trial (albeit, a small one) of ultra-rapid-acting insulins. Delivered via pumps to 42 type 1 patients, Adocia’s phase 3-ready BioChaperone Lispro demonstrated significantly faster offset vs. Novo Nordisk’s next-gen Fiasp (faster-acting insulin aspart), with 210 minutes late time to half-maximum glucose infusion rate vs. 228 minutes, respectively (18-minute difference, p=0.0017). Onset time was similar between the two insulins, with mean metabolic effect within the first hour of 162 mg/kg for BioChaperone Lispro vs. 154 mg/kg for Fiasp (non-significant p-value).

Moreover, Adocia’s candidate was superior to Novo Nordisk’s NovoLog (insulin aspart) for both onset and offset time, corroborating previous findings that BioChaperone Lispro is significantly faster-acting than Lilly’s Humalog (insulin lispro). Metabolic effect within the first hour was 63% higher with BioChaperone Lispro vs. NovoLog (162 mg/kg vs. 99 mg/kg, p<0.0001). Mean offset time was 232 minutes with NovoLog, significantly slower than 210 minutes with BioChaperone Lispro (p=0.002). These results position Adocia’s candidate within the emerging class of ultra-rapid-acting insulins.

The company aims to present full results at a major meeting in 2018 (very possibly ADA), and we look forward to a deeper dive on the comparative PK/PD profiles of the ultra-rapid-acting insulins. Interestingly, it seems like faster-offset may be more of a differentiating factor than faster-onset. When MannKind’s inhaled insulin Afrezza received an ultra-rapid label claim in October, management emphasized the value of a shorter tail in reducing post-meal hypoglycemia risk. And on a call with our team, Adocia management suggested that Fiasp’s tail is effectively “superimposable” with NovoLog’s based on these recent results, despite it being a more advanced, next-gen product. Fiasp’s EMA product information lists late time to half-max glucose infusion rate ~nine minutes faster than NovoLog. This head-to-head study found a four-minute difference, and the 18-minute mean difference between BioChaperone Lispro and Fiasp is a meaningfully greater jump, with positive implications for patient experience – but we note that this needs to be confirmed in a larger, phase 3 trial.

Next Steps for BioChaperone Lispro

• Adocia will meet with FDA sometime next year to discuss a phase 3 program, and the company continues to seek a development/commercialization partner, though a go-alone pathway is not off the table. Lilly terminated its licensing agreement for BioChaperone Lispro in January of this year, choosing instead to focus on its own internally-developed ultra-rapid insulin candidate, now in phase 3. In spite of this, Adocia remains wholly committed to BioChaperone Lispro: “We believe this product is phase 3-ready,” management shared on a call with our team, citing seven previous studies conducted in partnership with Lilly. The candidate has been well-characterized with consistent results for pumps and MDI, and could reach a broad spectrum of patients across type 1 and type 2 diabetes. BioChaperone Lispro could bring a new level of safety to mealtime insulin – hypoglycemia risk should fall substantially with a much shorter post-meal insulin tail, and this will be an important outcome to assess in phase 3. Management recognized the value of glycemic outcomes beyond-A1c, explaining that Adocia wants to be “on the cutting-edge” of this movement in its phase 3 program and beyond (in real-world evidence).
• Based on the efficacy BioChaperone Lispro has shown in pump studies, management pointed to potential applications in closed loop. Faster-offset with less residual hypoglycemia risk could be an appealing option for an automated system, allowing for tighter control, higher precision algorithms, and more safety. During our call, Adocia management expressed distinct curiosity for how BioChaperone Lispro might compare to Fiasp or to Lilly’s phase 3 ultra-rapid-acting insulin in closed loop. This may not be the primary focus of the pivotal phase 3 program, but management suggested that it’s certainly on the table as clinical development continues.
• Speaking to the competitive landscape, management seemed confident that BioChaperone Lispro would be able to compete commercially with Fiasp; we do note that phase 3 trials for Adocia’s candidate have yet to begin, while Fiasp will be launched in the US in 1Q18. Novo Nordisk’s product hasn’t been approved for pump use in the US, which could set BioChaperone Lispro apart, and management also alluded to marginal benefits seen with Fiasp over NovoLog in the phase 3 Onset program. In our view, the potential for Novo Nordisk’s Fiasp to improve patient quality of life and outcomes in the real world over NovoLog is substantial (especially since Fiasp is priced on par to NovoLog, which should expand access), but we do wonder how a ~nine-minute difference in late time to half-max glucose infusion rate compares to an ~18-minute difference from the patient perspective. How clinically-meaningful is this? Adocia acknowledged that Afrezza is very fast, but also very different in terms of use case, because (as one example) inhaled insulin wouldn’t necessarily be part of closed loop. Based on phase 1 and phase 2 results, management asserted that BioChaperone Lispro definitely belongs in this emerging category of ultra-rapid-acting prandial insulins.

-- by Payal Marathe and Kelly Close