insulin peglispro (LY2605541) / Eli Lilly - LARVOL DELTA

Accurate Collection of Reasons for Treatment Discontinuation to Better Define Estimands in Clinical Trials. (PubMed, Ther Innov Regul Sci) - P2, P3 | "This research provides insight and directions on how to optimize the CRF for recording treatment discontinuation. Further work needs to be done to build the learning into Clinical Data Interchange Standards Consortium standards."

Journal • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

Investing profits from the war on obesity (SeekingAlpha) - Arena shares have surged from $2 to trade at $9.50 in recent months; Vivus shares have soared from $12 to trade at $22 after the news of FDA approval; Orexigen shares have moved from $3 to around $5.5 per share; Eli Lilly shares are trading at $44 with a 4.42% dividend yield

Stock price • Diabetes

Pipeline update (Eli Lilly) - P2 data

P2 data • Diabetes

Better glycemic control and weight loss with the novel long-acting basal insulin LY2605541 compared with insulin glargine in type 1 diabetes: A randomized, crossover study (Diabetes Care) - P2, N=137; NCT01049412; Pubmed ID: 23193209; "Fasting blood glucose variability and A1C were reduced with LY2605541 compared with insulin glargine (both P < 0.001). Mealtime insulin dose decreased with LY2605541 and increased with insulin glargine. Mean weight decreased 1.2 kg with LY2605541 and increased 0.7 kg with insulin glargine (P < 0.001)."

P2 data • Diabetes

Pharmacokinetics (PK) of the novel, long-acting basal insulin LY2605541 in subjects with varying degrees of renal function (ADA 2012) - Presentation time: 6/9/2012 11:30:00 AM; Anticipated presentation at ADA 2012

Anticipated data presentation • Diabetes

Improved glycemic control despite reductions in bolus insulin doses with basal insulin LY2605541 compared with basal insulin glargine in patients with type 1 diabetes (ADA 2013) - Presentation time: Sat 6/22 11:30 AM – 1:30 PM; Abstract#915-P; P2, N=108; “LY had lower daily mean blood glucose compared with GL (143.1 mg/dL vs. 151.7 mg/dL; p<0.001)…The rate of total hypoglycemia events was higher for LY vs. GL (9.2 vs. 8.1 events/30d; p=0.074), but the rate of nocturnal hypoglycemia events was lower (0.9 vs. 1.2 events/30d; p=0.007)…”

P2 data • Diabetes

Reduced nocturnal hypoglycemia and weight loss with novel long-acting basal insulin LY2605541 compared with insulin glargine in patients with type 2 diabetes (ADA 2012) - Presentation time: 6/11/2012 4:30:00 PM; Anticipated presentation at ADA 2012

Anticipated data presentation • Diabetes

Better glycaemic control and weight loss with the novel long-acting pegylated basal insulin LY2605541 compared with insulin glargine in patients with type 1 diabetes (EASD 2012) - Publication-only abstract; P2, N=137; NCT01049412; Fasting BG variability (p<0.001) & HbA1c (p<0.001) were reduced with LY2605541(LY) vs. GL; Prandial insulin dose was reduced during LY treatment & increased with GL (p<0.001); LY provided greater improvements in glycaemic control & reduced nocturnal hypoglycaemia vs. GL in T1D

P2 data • Diabetes

Steady-state pharmacokinetics and glucodynamics of the novel, long-acting basal insulin LY2605541 dosed once-daily in patients with type 2 diabetes mellitus. (Diabetes Obes Metab) - PMID: 24118909; P1, N=18; NCT01877265; Sponsor: Eli Lilly; “Across dose levels t1/2 ranged from 44.7-75.5 hours (~2-3 days). As steady-state was achieved, there were dose-dependent reductions in the prandial insulin dose and in fasting blood glucose, which decreased to 60-100 mg/dL across dose levels. Within-patient variability was <14% and <26% for the AUC of the 8-point blood glucose profile and fasting blood glucose, respectively.”

P1 data • Diabetes

A randomized, controlled study of once daily LY2605541, a novel long-acting basal insulin, versus insulin glargine in basal insulin-treated patients with type 2 diabetes (Diabetes Care) - P2, N=248; At 12 weeks, FBG (mean ± SE) was similar with LY2605541 and GL (118.2 ± 2.0mg/dL [6.6 ± 0.1mmol/L] vs. 116.9 ± 2.7mg/dL [6.5 ± 0.2mmol/L], p=0.433) as was A1C (7.0 ± 0.1 vs. 7.2 ± 0.1%, p=0.279).; Intraday blood glucose variability was reduced with LY2605541 (34.4 vs. 39.1mg/dL [1.9 vs. 2.2mmol/L], p=0.031); LY2605541 pts had weight loss (-0.6 ± 0.2kg, p=0.007), whereas GL pts gained weight (0.3 ± 0.2kg, p=0.662; treatment difference: -0.8kg, p=0.001)

P2 data • Diabetes

A Study Comparing LY2605541 With Insulin Glargine as Basal Insulin Treatment (clinicaltrials.gov) - P3; N=380; Active, not recruiting; Sponsor: Eli Lilly and Company; Recruiting -> Active, not recruiting

Enrollment closed • Biosimilar • Diabetes

Weight loss and lower nocturnal hypoglycaemia with novel long-acting basal insulin LY2605541 versus insulin glargine in patients with type 2 diabetes (EASD 2012) - Publication-only abstract; P2, N=NA; NCT01027871; At Week 12, LY2605541 vs. GL resulted in similar mean FBG (p=0.433) & mean HbA1C (p=0.279); Intra-day blood glucose variability was reduced with LY (p=0.031); LY pts had significant mean weight loss (p=0.007), while GL pts gained weight (p=0.001); LY provided similar glycaemic control, with reduced intra-day variability & lower nocturnal hypoglycaemic events vs. GL in pts with T2D

P2 data • Diabetes

Lilly gets ready to compete with its late-stage diabetes pipeline (Pink Sheet - Informa) - "...four new diabetes drugs on the market by 2016...also conducting a large cardiovascular outcomes study that is expected to report out in 2018...Lilly/BI plan to submit their insulin glargine for regulatory approval for type 1 and type 2 diabetes later this year..."

Anticipated launch • Anticipated P3 data • Anticipated regulatory • Diabetes

LY2605541 exhibits a flatter glucodynamic profile than insulin glargine at steady state in subjects with type 1 diabetes (EASD 2013) - Presentation time: Thu, Sep 26; 12:30 PM; Abstract #1030; P2, N=23; NCT01049412; Sponsor: Eli Lilly; "Mean hypoglycaemia episodes/30 days were 2.7 ± 2.3 (total) and 0.5 ± 0.8 (nocturnal) for LY and 3.0 ± 2.4 (total) and 0.7 ± 1.1 (nocturnal) for GL, p=0.11 (total) and 0.43 (nocturnal). Mean GIR normalized to unit of insulin was less for LY than GL and persistent over 24 hours."

P2 data • Diabetes

A study of how LY2605541 and insulin glargine affect the breakdown of fat and sugar in type 1 diabetics (clinicaltrials.gov) - P1, N=32; Sponsor: Eli Lilly; Not yet recruiting; New P1 trial.

New P1 trial • Diabetes

Reduced nocturnal hypoglycemia and weight loss with novel long-acting basal insulin LY2605541 compared with insulin glargine in patients with type 2 diabetes (ADA 2012) - Presentation time: 6/11/2012 4:30:00 PM; P2, N=575; For LY v GL, mean ± SE FBG was 147 ± 3 v 140 ± 4mg/dL, A1C was 7.7 ± 0.1 v 7.8 ± 0.1%, and weight was 90.7 ± 1.4 v 89.7 ± 2.1kg; At wk 12, LY v GL resulted in similar mean FBG (118 ± 2 v 117 ± 3mg/dL, p=.433), and mean A1C (7.0 ± 0.06 v 7.2 ± 0.09%, p=0.279); LY pts had mean weight loss (-0.58 ± 0.16kg, p=.007), while GL pts gained weight (0.31 ± 0.18kg, p=0.66; LS mean difference: -0.84kg, p=0.001)

P2 data • Diabetes

A Study of LY2605541 and Glargine on Fats in Participants With Type 1 Diabetes (clinicaltrials.gov) - P1; N=15; Completed; Sponsor: Eli Lilly and Company; Active, not recruiting -> Completed

Trial completion • Atherosclerosis • Biosimilar • Diabetes • Dyslipidemia

A study comparing LY2605541 with insulin glargine as basal insulin treatment (clinicaltrials.gov) - P3, N=380; Sponsor: Eli Lilly; Not yet recruiting -> Recruiting.

Enrollment open • Diabetes

Eli Lilly and the state of the insulin battle (SeekingAlpha) - FDA delayed the decision on Tresiba until 2013; P3 clinical data for the Lilly drug LY2605541 is expected in 2013

Anticipated P3 data: top line • Regulatory • Diabetes

A study of LY2605541 and glargine and exercise in participants with type 1 diabetes (clinicaltrials.gov) - P1, N=76; Sponsor: Eli Lilly and Company; Not yet recruiting -> Recruiting.

Enrollment open • Diabetes

A study of LY2605541 in participants with type 1 diabetes mellitus (IMAGINE 7) (clinicaltrials.gov) - P3, N=170; Sponsor: Eli Lilly and Company; Not yet recruiting -> Recruiting.

Enrollment open • Diabetes

Novel pegylated basal insulin LY2605541 has a preferential hepatic effect on glucose metabolism (ADA 2012) - Presentation Time: 6/11/2012 12:00:00 PM; At the end of the clamp, glucose rate of appearance (Ra) was suppressed by 1.6±0.3 and 2.3±0.2mg/kg/min in CONTROL and LY, respectively (p<0.05), and unidirectional hepatic glucose uptake was 33% higher in LY than in CONTROL (p=0.06); Non-hepatic glucose uptake in LY increased less than in CONTROL (last hr: 0.7±0.3 vs. 2.0±0.8mg/kg/min above basal)

Preclinical-animal • Diabetes

A Study of LY3192767 in Healthy Participants (clinicaltrials.gov) - P1; N=57; Completed; Sponsor: Eli Lilly and Company; Terminated ➔ Completed

Trial completion