exenatide DUROS subcutaneous delivery system (ITCA 650) / Servier, i20 Therap - LARVOL DELTA

i2o Therapeutics Names Kurt Graves Chairman and CEO, Announces Corporate Updates (Businesswire) - "An acquisition and integration of ITCA 650 and the Medici implant technology platform which is an investigational twice-yearly implantable GLP-1 for type 2 diabetes and was recently granted a public hearing on September 21 before an FDA Advisory Committee. The public hearing was granted by the Commissioner’s Office and FDA’s Chief Scientist."

M&A • Diabetes • Metabolic Disorders

META-ANALYSIS ASSESSING THE IMPACT OF PRIOR HEART FAILURE AND CHRONIC KIDNEY DISEASE ON THE CARDIOVASCULAR EFFICACY OF GLUCAGON-LIKE PEPTIDE-1 RECEPTOR AGONISTS. (PubMed, J Hypertens) - "GLP-1RAs seem to constitute a safe and efficacious treatment option in patients with T2DM and established or at high risk for atherosclerotic cardiovascular disease, while HF or CKD status at baseline do not substantially affect the observed cardio-protective effect against hard cardiovascular endpoints."

Journal • Retrospective data • Atherosclerosis • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetes • Dyslipidemia • Heart Failure • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

"Is justice delayed justice denied? The @US_FDA approach to a balanced fact- based assessment of continuous release exenatide (ITCA-650) https://t.co/wbDNgaik0N" (@DanielJDrucker)

Cardiovascular and mortality outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: A meta-analysis with the FREEDOM cardiovascular outcomes trial. (PubMed, Diabetes Metab Syndr) - "FREEDOM results should not influence current considerations about the benefits or harms of approved formulations of GLP-1 receptor agonists. There is also an ongoing debate about the safety of ITCA 650."

Journal • Retrospective data • Review • Cardiovascular • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Subcutaneous infusion of exenatide and cardiovascular outcomes in type 2 diabetes: a non-inferiority randomized controlled trial. (PubMed, Nat Med) - P3 | "Glucagon-like peptide 1 receptor agonists (GLP-1RAs) injected periodically have been shown to not increase and, for some members of this class, decrease the risk of cardiovascular events. In patients with type 2 diabetes with, or at risk for, ASCVD, ITCA 650 was non-inferior to placebo. A larger and longer-duration cardiovascular outcomes trial is needed to define more precisely the cardiovascular effects of ITCA 650 in this population."

Clinical • Head-to-Head • Journal • Atherosclerosis • Cardiovascular • Diabetes • Dyslipidemia • Gastrointestinal Disorder • Metabolic Disorders • Myocardial Infarction • Type 2 Diabetes Mellitus

ITCA 650 Improves Glycemic Control and Reduces the Need to Advance Antidiabetes Therapy (ADA 2017) - "...Significant reductions in HbA1c and weight occurred in 2 clinical trials: FREEDOM-1, a 39-week, placebo-controlled trial in pts on OADs and FREEDOM-2, a 52-week, study of ITCA 650 vs. sitagliptin (SITA) in pts uncontrolled on metformin... In uncontrolled T2D, ITCA 650 results in significantly improved and stable glycemic control without AT in the majority of patients."

Clinical • Biosimilar • Diabetes

ITCA 650 exenatide vs sitagliptin added-on to metformin: estimates of the need for further diabetes therapy (EASD 2017) - P3; "In conclusion, addition of ITCA 650 for 52 weeks led to better sustained glycemic control in uncontrolled T2D on metformin, significantly reducing the need for further therapy compared to addition of SITA."

Clinical • Diabetes

Effect of ITCA 650 on the PK of Acetaminophen (APAP) and Other Commonly Coadministered Drugs (ADA 2017) - "There was no effect of ITCA 650 on gastric emptying and no dosage adjustment is deemed necessary when ITCA 650 is co-administered with these commonly used drugs."

Clinical • Biosimilar • Diabetes

Promising molecules for treatment of hyperglycemia in patients with type 2 diabetes (PubMed) - Vnitr Lek - "New properties are brought by just the change of concentration (insulin glargine in a concentration of 300 U/ml), unexpected positive results are also brought by new fixed-ratio combinations of antidiabetics (fixed-ratio combination of insulin degludec and liraglutide, fixed-ratio combination of insulin glargine and lixisenatide). Also results of clinical studies appear that concern molecules already in use which facilitate the formulation of new recommendations regarding treatment type 2 diabetes.Key words: type 2 diabetes mellitus - dulaglutide - FGF 21 - imeglimin - insulin aspart - insulin degludek - insulin glargine - ITCA 650 - liraglutide - national information diabetes system - semaglutide."

Journal • Biosimilar • Diabetes

Continuous subcutaneous delivery of exenatide via ITCA 650 leads to sustained glycemic control and weight loss for 48 weeks in metformin-treated subjects with type 2 diabetes (J Diabetes Complications) - P2, N=155; NCT00943917; Sponsor: Intarcia Therapeutics; "At week 48, ≥64% of subjects with an HbA1c ≤7% at week 24 maintained an HbA1c ≤7%. The incidence of adverse events (AEs) was dose-related and ranged from 13.3% with 20μg/day to 37.5% with 80μg/day."

P2 data • Diabetes

Quintiles says new financing-partnership approach could replace 'old fashioned' outsourcing models (Outsourcing-Pharma) - Under the new model, in addition to providing researchers to work with the Intarcia team developing the "Duros" subcutaneous exenatide tech, Quintiles is providing financing for the project which, it claims, makes it a genuine partner rather than just a service provider

Company Statement • Diabetes

Long-term, injection-free treatment with ITCA 650, continuous subcutaneous delivery of exenatide via DUROS device, leads to sustained improved glycemic control and weight loss for 48 weeks in metformin-treated type 2 diabetes (ADA 2011) - Presentation time: June 28, 2011: 10:45 AM - 11:05 AM; Abstract not available

Diabetes

"Among the 2017 surprises #diabetes ITCA650 @intarcia poised to solve the persistence adherence problem @T2D receives CRL @US_FDA" (@DanielJDrucker)

Biosimilar • Diabetes • Metabolic Disorders

A study to evaluate ITCA 650 compared to sitagliptin as add-on therapy for the treatment of type 2 diabetes (clinicaltrials.gov) - P3, N=500; Sponsor: Intarcia; Not yet recruiting -> Recruiting; Start date: Feb 2013 -> May 2013; Completion date: Jul 2014 -> Feb 2015.

Enrollment open • Trial completion date • Trial initiation date • Diabetes

Efficacy and safety of ITCA 650, an injection-free GLP-1 RA, in patients with type 2 diabetes: a pooled analysis of phase 3 studies (EASD 2018) - "As an investigational product for the treatment of type 2 diabetes (T2D), ITCA 650 provides a continuous subcutaneous infusion of exenatide over 3 or 6 months.Materials and An integrated analysis of efficacy and safety was conducted from 2 double-blind, randomized, Phase 3 studies, which evaluated pooled data with ITCA 650 20/60 mcg/d vs. placebo or sitagliptin for the treatment of patients with T2D, inadequately controlled on antidiabetic drugs. The results are consistent with results observed from individual Phase 3 studies, which demonstrated that ITCA 650 is effective for lowering HbA1c and weight, for achieving a composite of HbA1c/weight reduction and target HbA1c "

P3 data • Retrospective data • Biosimilar • Diabetes • Metabolic Disorders

Intarcia presents positive ITCA 650 phase 2 study results for type 2 diabetes at EASD (PRNewswire) - P2, N=155; Incremental reductions in HbA1c and weight were observed across all treatment arms at week 24; Treatment regimen involving a 20mcg/day starting dose with a transition to 60mcg/day has been selected for a P3 trial, anticipated to begin in early 2011

Anticipated P3 trial • Anticipated presentation

Intarcia Therapeutics raises $5M to treat long-term conditions (Reuters) - Intarcia raised $5M to treat long term conditions and plans to conduct another phase of its diabetes treatment study to confirm the results later in 2010;

Diabetes

Effectiveness and safety of ITCA 650 vs currently available GLP-1 RAs in type 2 diabetes: a phase IIIb, pragmatic RCT (IDF 2017) - "Use of NWEH systems to monitor safety and collect clinical endpoints offers minimal disruption to patients and permits the trial to be performed in an environment that mimics use of these medicines in the real world. This innovative study will assess the clinical, economic, and patient-reported impact of the novel mode of administration of ITCA 650 in patients with T2D as compared with other GLP-1 RAs."

Clinical • P1 data • P3 data • Real-World Evidence • Diabetes • Metabolic Disorders

Randomized trial of continuous subcutaneous delivery of exenatide by ITCA 650 versus twice-daily exenatide injections in metformin-treated type 2 diabetes (Diabetes Care) - PMID: 23645886; P2, N=155; NCT00943917; Sponsor: Intarcia therapeutics: "...mean change in HbA1c from a mean baseline of 7.9-8.0% was -0.98, -0.95, and -0.72% for the 20 and 40 μg/day ITCA 650 and Ex-BID groups, respectively, with 63, 65, and 50% of subjects achieving HbA1c levels ≤7% (P < 0.05)...significant (P < 0.05) reductions in HbA1c (∼1.4% from baseline) were achieved with 60 and 80 μg/day ITCA 650, and 86 and 78% of subjects achieved HbA1c ≤7%..."

P2 data • Diabetes

A randomized, open-label, multicenter, 4-week study to evaluate the tolerability and pharmacokinetics of ITCA 650 in patients with type 2 diabetes (Clin Ther) - P1, N=44; NCT01798264; Sponsor: Intarcia Therapeutics; "...significant (P < 0.05) decreases in fasting plasma glucose levels, 2-hour postprandial glucose levels, and glucose AUC curve were seen in all treatment groups. HbA1c levels also decreased significantly (P < 0.001) in all 4 treatment groups. Weight was significantly (P < 0.05) lowered in the 40- and 80-μg/d groups."

P1 data • Diabetes

Generalizability of glucagon-like peptide-1 receptor agonist cardiovascular outcome trials enrollment criteria to the US type 2 diabetes population. (PubMed, Am J Manag Care) - P3, P4; "Most adults with T2D in the United States would have qualified for enrollment into at least 1 of the GLP-1 RA CVOTs evaluated. EXSCEL had the most generalizable eligibility criteria of these trials and ELIXA the least."

Clinical • Journal

"Cannot wait for ITCA 650 to launch! The countdown begins!" (@OxygenHealth1)

Exenatide implant therapy in diabetes. (PubMed, J Pak Med Assoc) - "The article discusses the pharmacodynamics and pharmacokinetics of ITCA 650, and suggests how it's benefits can be utilized in clinical practice. It lists the advantages and limitations of the device, and shares tips for its rational use in type 2 diabetes care."

Journal