ITCA-650, a subdermal osmotic implant that provides continuous delivery of exenatide, is being developed by Intarcia Therapeutics for the treatment of type 2 diabetes (T2D). The device provides continuous and consistent exenatide therapy in a 3-month initiation dose, followed by consecutive 6-month maintenance doses. Exenatide is a glucagon-like peptide-1 (GLP-1) receptor agonist that is currently marketed globally by AstraZeneca as a twice-daily and a once-weekly self-injection therapy for T2D. If approved, ITCA-650 will be the only twice-yearly, injection-free GLP-1 therapy. However, physicians will have to be trained in inserting and removing ITCA-650, a process that could slow down its rollout should it be approved. ITCA-650’s Phase 3 FREEDOM program began in February 2013 and consisted of four trials together enrolling over 5,000 patients. The largest of the Phase III trials was a 4,000-patient Cardiovascular Outcome Trial (CVOT) (FREEDOM-CVO) that completed in April 2016, with top-line results indicating that ITCA-650 met its primary endpoint of cardiovascular (CV) safety.1 The New Drug Application (NDA) for ITCA-650 in the treatment of T2D was accepted by the Food and Drug Administration (FDA) on February 3, 2017, but on September 27, 2017, the FDA issued a Complete Response Letter (CRL). Intarcia Therapeutics announced they do not anticipate the need to conduct new pivotal trials to satisfy the requirements of the FDA. Furthermore, Intarcia reported receiving clear and constructive guidance regarding manufacturing aspects of the CRL from the FDA, and they are on a clear path to move forward.2
Based on Decision Resources Group’s (DRG) primary research,3 surveyed primary care physicians (PCPs) and endocrinologists report a moderate level of unmet need for new T2D treatments with a reduced dosing burden. These physicians also indicate that they are moderately satisfied with the performance of current T2D therapies on this metric. Responses from endocrinologists surveyed by DRG also suggest that the key differentiating feature on dosing burden is not how the drug is administered but how frequently it must be administered. DRG believes ITCA-650’s significantly reduced dosing frequency, compared with current T2D therapies, puts it at an advantage. In fact, PCPs and endocrinologists surveyed by DRG4 ranked better dosing schedule as a top factor to influence their prescribing of ITCA-650 over existing GLP-1 receptor agonists. However, a sizeable percentage of physicians indicate that they would not prescribe this product. Further, a disparity exists between physician types, with endocrinologists even less likely to prescribe ITCA-650 than PCPs. The most common reason behind this response is endocrinologists’ failure to see any advantages of the agent’s risk benefit profile over currently marketed agents. In contrast, PCPs’ main reason is safety concerns.
Key Factors Influencing the Prescribing of ITCA-650 Over Existing GLP-1 Receptor Agonists
ITCA-650 should guarantee patients’ compliance with treatment, which is a major concern for physicians managing T2D patients, particularly those with multiple comorbidities. The majority of surveyed endocrinologists consider dosing burden as moderately important in influencing their prescribing decisions in T2D. This response may reflect the wide range of patients with T2D, including older patients with multiple comorbidities already taking several medications. These patients require a more complex and individualized treatment approach. Consequently, new antidiabetic agents that offer simple, more-convenient dosing are highly desirable. Furthermore, given the importance that surveyed endocrinologists and PCPs ascribed to this attribute, they may favor emerging therapies with unique delivery profiles such as ITCA-650.
ITCA-650’s prospects are encouraging: in the FREEDOM-2 Phase III trial, significantly more ITCA-650-treated patients achieved reductions in HbA1c greater than 0.5%, and body weight greater than 2 kg, compared with sitagliptin (61% vs. 28%).5 ITCA-650’s continuous delivery approach is expected to carry improved adherence benefits, lack of frequent injections, and reduced side effects such as nausea which is partially attributed to post-injection peaks of exenatide in the blood. The 100% compliance offered by ITCA-650 will not only play a significant role in physician’s prescribing decisions, it may also appeal to healthcare payers. ITCA-650 has the potential for favorable formulary tier placement, a factor that could significantly affect uptake in cost-conscious T2D markets.
To access DRG’s Type 2 Diabetes content, click here.
5 Rosenstock J, Denham D, Prabhakar R, Azeem R, Kjehms L, Baron M. Superior efficacy of ITCA 650 vs sitagliptin in uncontrolled type 2 diabetes on metformin: the FREEDOM 2 randomized, double-blind, 1-year study. Diabetes. 2016; 65(suppl1):183-OR.