LYON, France & INDIANAPOLIS—Adocia and Eli Lilly and Co. announced in late April positive top-line results from a Phase 1b clinical trial under the Adocia-Lilly partnership evaluating BioChaperone Lispro, an ultra-rapid formulation of insulin lispro licensed to Lilly. This formulation uses Adocia’s proprietary technology BioChaperone, designed to accelerate insulin absorption.
This study was the first to evaluate BioChaperone Lispro in people with type 2 diabetes (T2D), who, unlike people with type 1 diabetes (T1D), may show various degrees of disease progression, endogenous insulin production and insulin resistance. The 14-day outpatient study aimed to compare the effect of multiple daily injections of BioChaperone Lispro and Humalog (insulin lispro rDNA origin) on postprandial glycemic control relative to solid standardized meals, when injected at the time of the meal, in 51 people with T2D.
“We are delighted to also observe in people with type 2 diabetes a significantly faster insulin absorption with BioChaperone Lispro compared to Humalog, as was the case in our previous studies in people with type 1 diabetes,” said Dr. Simon Bruce, Adocia’s chief medical officer. “This acceleration translated, across more than 200 meal tests, into a significant reduction in postprandial glucose excursion over the first two hours. These results underscore that BioChaperone Lispro delivers a similar performance in people with type 1 or type 2 diabetes. This study also reinforces comparability in the BioChaperone Lispro safety profile to that of Humalog.”
Based on a post-hoc analysis, BioChaperone Lispro demonstrated a statistically significant 22-percent reduction in blood glucose excursion over the first two hours compared to Humalog. The pharmacokinetic profile of BioChaperone Lispro U100 was consistent with that observed in previous studies in people with T1D, demonstrating a statistically significant 83-percent increase in exposure to insulin lispro over the first 30 minutes compared to Humalog.
“We are encouraged by the results of this trial,” said Dr. Thomas Hardy, senior medical director of endocrinology at Lilly. “In addition, we are pleased with the expeditious progress of our joint program with Adocia.”
Just a little over a month before, the two companies had announced positive topline results from a Phase 1b clinical trial for BioChaperone Lispro, which was the first outpatient 14-day study comparing the effect of multiple daily injections of BioChaperone Lispro and Humalog on postprandial glycemic control relative to solid standardized meals in 36 patients with T1D.
At the beginning of the study, when injected at the time of meal, BioChaperone Lispro demonstrated a statistically significant 31-percent reduction in blood glucose excursion over the first two hours compared to Humalog. After 14 days of treatment for each treatment, BioChaperone Lispro also demonstrated a statistically significant 42-percent reduction in blood glucose excursion over the first two hours compared to Humalog, when injected at the time of the meal. This last result demonstrates the robustness of the performance of BioChaperone Lispro on a two-week period.
“This was an important study and provides our first experience with repeat doses of this ultra-rapid insulin formulation in an outpatient setting,” said Hardy. “We are encouraged by these results and look forward to seeing the results of additional, ongoing studies.”
In the T2D and the T1D studies, both BioChaperone Lispro and Humalog were similarly well tolerated throughout the 14 days. No new or unexpected safety findings were observed and no local reactions were seen on the site of administration for either treatment.
The news regarding BioChaparone Lispro could be a particularly good thing, given some weakness on the Humalog front. In analyzing Lilly’s recent Q1 financial report, Leerink Partners noted that total revenue of $4.87 billion was in line with consensus ($4.84 billion), but $125 million below Leerink’s forecast ($4.99 billion), with Seamus Fernandez and colleagues at Leerink writing: “The biggest surprise in sales figure was a significant drop in Humalog sales ($606 million vs. consensus $722 million and Leerink estimate of $745 million).”
Not that Lilly is doing bad on the diabetes front, Leerink noted. Sales of Trulicity (a once-weekly GLP 1 for T2D that helps activate the body’s ability to release its own insulin) “came in $34 million above our forecast, and this agent is tracking to become a blockbuster product.” In addition, Jardiance (an oral T2D medicine that helps control blood sugar levels by helping the kidneys get rid of glucose from the bloodstream) sales “beat our estimate by $13 million, which is encouraging.”
Leerink also acknowledged that Lilly’s profitability “was clearly dragged down by government rebate volatility, which significantly dragged down Humalog growth.”
The Adocia-Lilly story has had its own ups and downs over the years. Lilly made a deal with Adocia in 2011 to co-develop a rapid-uptake insulin, and then about 18 months later, despite a successful Phase 1 trial, Lilly walked away from the deal without any real explanation. Forging ahead on its own, Adocia turned that insulin into what became known as BioChaperone Lispro and showed in a Phase 2a study that the insulin took effect faster than Lilly’s Humalog.
So, in 2014, Lilly came back to the table with a collaboration deal worth up to $570 million, under which Lilly would pay its French partner $50 million up front for the exclusive rights to BioChaperone Lispro, which is a synthetic insulin tied to Adocia’s proprietary delivery system, plus $280 million more in payments attached to development and regulatory milestones and another $240 million contingent on product sales.