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Four New Drugs Waiting for Approval That Can Change The Diabetes Landscape (Part 2)

May 12, 2018

New exciting treatment options currently being trialed could change the way the disease is treated long term: Oramed Pharmaceuticals’ oral insulin ORMD-0801 and Intarcia Therapeutics Itca-650 subdermal osmotic implant.

Oral Insulin


Oramed Pharmaceuticals announced just recently that it is initiating a Phase IIb trial for its oral insulin candidate ORMD-0801 in 240 insulin-naïve patients with type II diabetes over 90 days with a primary endpoint of HbA1c reduction. This will be the first clinical trial of its type for an oral insulin pill.

There are two reasons this trial should be watched closely. First of all, obviously, to see if oral insulin can lower 90-day blood sugar levels to below 7%. The endpoint is mean change in HbA1c from baseline to 12 weeks, but for any Phase III trial, HbA1c will probably have to go below the 7% target to be approved. The second reason is to see the dosages required to lower HbA1c to that target.

A previous Phase II trial used 16mg and 24mg doses as active comparators for lowering pooled nighttime glucose. These doses are orders of magnitude higher than what is required for injectable insulin, which is measured in IUs rather than milligrams. 1 IU of insulin is equivalent to 0.0347mg if human insulin, which means that 16mg is about 461 IUs. Patients start off insulin treatment with about half a unit per kilogram of body weight per day. Assuming 80kg bodyweight, that’s 40 units a day, which means the 16mg is about 10x as high in the amount of insulin required per dose. This makes sense given that much of the insulin is destroyed in the GI tract.

There are many unknowns at this point, but these candidates do have the potential to change the way diabetes will be treated in the coming decade. Besides results, which obviously matter, whether any of them will succeed in the market if approved depends a lot on cost, the big unknown at this point.


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.  It’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. The New Drug Application (NDA) for ITCA-650 in the treatment of T2D was accepted by the 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. Study results are here

Responses from endocrinologists suggest that the key differentiating feature on dosing burden is not how the drug is administered but how frequently it must be administered. They believe that ITCA-650 significantly reduced dosing frequency, compared with current T2D therapies, puts it at an advantage. In fact, PCPs and endocrinologists surveyed 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. As the product is exenatide, which has already approved and in the market, it is really all about the delivery system that they are looking at and, .the FDA should be making a decision this year, 2018.

Practice Pearls:

  • New treatment options currently being trialed could change the way the disease is treated long term.
  • Novo Nordisk’s oral semaglutide could increase patient compliance and help delay the need for direct insulin treatment.
  • Opko’s oxyntomodulin candidate is the leader in a new class of dual GLP-1 and glucagon receptor agonists.
  • Oramed just started a Phase 2 trial on an oral insulin candidate.
  • ITCA-650 is waiting for final FDA approval after addressing the FDA concerns.

Diabetes Care 2018 Feb; 41(2): 333-340. https://doi.org/10.2337/dc17-1306

OraMed.com   Opko.com   Clinicaltrials.gov