Oral Insulin (ORMD-0801) Close to Reality

An interview with Oramed Pharmaceuticals CEO and Principal Investigator about a Phase 2b study of its oral insulin, ORMD-0801, and the latest clinical results.

This is an exciting time with many new treatments and devices becoming available for treating diabetes.

The first major treatment for diabetes took place over 107 years ago with the discovery of insulin. Then by chance in 1942, Marcel J. Janbon discovered the antidiabetic effects of sulfonylurea. Then it took us more than 50 years, until 1995, for the second drug to be approved for type 2 diabetes, metformin. Today, there are many possible combinations to treat type 2 diabetes.

Now, we may have another new drug — or is it new? A Phase 2b study in patients with type 2 diabetes (T2DM) was completed for what looks likely to be the first oral form of insulin (ORMD-0801), and Diabetes in Control (DIC) had the opportunity to interview and discuss the results with the developing company, Oramed Pharmaceuticals, CEO Nadav Kidron and Dr. Joel Neutel, Principal Investigator of the study.

DIC: Let’s start with the latest study results from the first cohort of the Phase 2b study.

Dr. Neutel tells us that the Phase 2b study was a placebo-controlled, double-blind, randomized, 90-day dose-ranging trial of ORMD-0801 in type 2 diabetes (T2D) patients who had inadequate glycemic control while taking oral antihyperglycemic agents. The study assessed the change in A1C – the primary efficacy endpoint – from baseline to week 12, as well as safety endpoints when ORMD-0801 was given in different regimens across a dose range.

Results showed statistically significant reductions in A1C and an excellent safety profile. In our discussion with Mr. Kidron and Dr. Neutel, they explained that many of the patients in the Phase 2b study were also on other diabetes drugs, which is difficult to control.

Regarding safety, they confirmed that the oral insulin delivery is exceptionally safe. Mr. Kidron explained the side effect profile was no different in the actively treated patients compared to those treated with placebo, and there was also no increase in hypoglycemia or weight when compared to placebo over the three month treatment period.

DIC: Because it was dose-ranging, can you outline the specifics of these efficacy levels, so our readers understand?

Patients who were randomized to once-daily ORMD-0801 achieved a reduction in mean A1C of 0.60% from baseline or a reduction of 0.54% adjusted for placebo (p-value = 0.036). This 0.54% reduction in A1C is considered clinically meaningful because it improved glucose control, without the complication of hypoglycemia.

Dr. Neutel says that this study demonstrates ORMD-0801 is effective when used once or twice daily, but when using it three times a day with a total daily dose of 96mg, the results did not reach statistical significance (p-value 0.093). Dr. Neutel and Mr. Kidron speculate that this reduced therapeutic effect occurred when increasing the dose due to the maximum capacity of the liver to absorb insulin. The lower-dose arms performed better in the Phase 2b study, indicating that lower doses would be more impactful clinically and, as a result, could potentially ease prescribing and compliance once FDA reviews it.

DIC: Speaking of absorption, can your oral insulin be taken with food, or only on an empty stomach?

Mr. Kidron confirmed that current results, as well as additional studies the company has performed, have shown that oral insulin can be taken before meals.

DIC: Does this mean that, if approved, patients will no longer have to inject insulin?

Oramed’s oral insulin should improve diabetes management and better control the disease by allowing for insulin treatment to begin potentially earlier in the treatment paradigm. This would enable overall better health for the patient, allowing them to achieve recommended glycemic targets, thereby reducing the risk of microvascular complications such as retinopathy (causes vision impairment) and nephropathy (kidney disease). Rather than insulin being the last line of treatment (via injections), oral insulin could be administered much earlier, which aligns with the recommendations of the ADA and EASD.  

According to Oramed, this is all possible because oral insulin is a more physiological true method of treatment. Oral insulin is intestinally absorbed and therefore works differently in the body than injectable insulin. Oral insulin mimics insulin’s natural location and gradients in the body by the first pass through the liver before entering the bloodstream, therefore reducing gluconeogenesis as its main function.

Ultimately, oral insulin would unlikely substitute or eliminate the need for injectable insulin but could have very positive effects in improving the management of care.

Oramed’s oral insulin candidate ORMD-0801 is being clinically evaluated in both T2DM and Type 1 diabetes (T1DM).

DIC: Can you tell us more about Oramed’s plan and next steps for its oral insulin, including plans for Phase 3 studies and FDA regulatory pathway?

Mr. Kidron told us that the company expects data from the second cohort of its Phase 2b study in Q1 2020.  Data from the second cohort will evaluate the efficacy of lower doses to best identify the optimal dose for the planned Phase 3 study.

Phase 3 trials are typically much more robust and involved with a larger number of patients because they are used to confirm and expand upon the safety and efficacy reported in Phase 1 and 2 studies. For Oramed’s Phase 3 study, Mr. Kidron told us that both type 1 and type 2 patients who were not meeting goals on current medications would be included.   

DIC: Anything else you’d like to add?

Mr. Kidron explained that Oramed’s oral insulin has the potential to create a new paradigm in the treatment of diabetes by oral delivery of insulin at an earlier stage of treatment, potentially slowing disease progression and delaying or even eliminating late-stage complications.

Practice Pearls

• The use of oral insulin could be clinically beneficial to patients with type 1 or type 2 diabetes, decreasing A1C without hypoglycemia or weight gain.
• Oramed’s oral insulin is farthest along in clinical development in the industry and has the potential to be the first commercial oral insulin capsule for the treatment of diabetes.
• In this Phase 2b study, treatment with Oramed’s unique oral insulin ORMD-0801 met the study’s primary endpoints, demonstrating a statistically significant reduction in HbA1c with an excellent safety profile.
• The next steps include results from the second cohort of the Phase 2b, which evaluated a lower dose range, and results are expected in the first quarter of 2020. 

 

 

See more about oral insulin research.