Some are on the cusp of commercializing transformative approaches for patients.
We spoke to executives at Oramed Pharmaceuticals and Novo Nordisk to get the low-down on the R&D developments at both companies in terms of advancing the delivery of insulin to diabetes patients, reducing the burden of disease management for such individuals.
Oral insulin: The holy grail?
Oramed is looking to develop oral diabetes medications that are currently injectables.
Its says its proprietary lead candidate, ORMD-0801, has the potential to be the first commercial oral insulin capsule for the treatment of diabetes.
Nadav Kidron, CEO of Oramed Pharmaceuticals, reported on the company’s goals for 2022 in this respect:
“This year is on track to be a very exciting year for Oramed and oral insulin as we expect to complete enrollment of our Phase 3 trial of oral insulin for Type 2 diabetes (T2D), and to share topline data from ORA-D-013-1 in Q4 2022.
“Our current clinical focus is on T2D for oral insulin and we are targeting the end of next year to file a BLA application.”
In addition, the company expects to complete enrollment for its oral insulin NASH trial with initial data this year.
Oral insulin has a number of potential benefits, explained Kidron, including a more natural method of delivery.
“Oramed’s oral insulin – recombinant human insulin – unlike the injectable insulin, mimics the body’s endogenous insulin and regulates glucose from the liver. In addition, with an oral insulin pill, patient compliance will likely be much higher – studies have shown that people would prefer a pill to a shot.
“Today, for type 2 patients, insulin is often a last resort medication, but with an oral insulin pill, insulin could be prescribed earlier on in the treatment paradigm which should have a positive impact on the patient’s overall health.”
Previous clinical trials showed a lowering of A1C levels, and importantly, there was no weight gain, or increase in hypoglycemic events, compared to placebo, or adverse side effects, he said. “The oral insulin has been safely dosed tens of thousands of times.”
Oramed’s patented oral delivery platform includes a special protective formula that protects the protein from being broken down by enzymes in the GI tract and includes absorption enhancers to help the insulin cross over the intestinal wall.
When asked about any potential risks for Oramed in terms of commercialization of its oral insulin capsule in relation to pricing, ensuring insurance company coverage and making sure physicians are not hesitant to prescribe oral insulin over injectables due to limited safety and efficacy data compared to injectable insulin, Kidron was very clear:
“Overall, we expect that an oral insulin capsule could be a first-choice medication for physicians and patients alike.”
The results of a survey support that outlook, he said. It showed that 85% of T2D patients polled indicated they were “extremely likely” or “very likely” to ask their doctors about ORMD-0801.
“As we progress with our Phase 3 trials we continue to be in active contact with stakeholders, including health care providers, payers and patients," added the CEO.
Weekly insulin injections: a new treatment paradigm?
Novo Nordisk has long been a pioneer in terms of innovation in the diabetes treatment space, said Mads Frederik Rasmussen, senior vice president of clinical drug development at that pharma giant.
And he explained why the company’s once-weekly Insulin icodec injection represents a new treatment paradigm for diabetes:
“Insulin first started being produced for the treatment of diabetes 100 years ago. Since then, there have been many large and small steps forward in innovation, such as the first purified insulin, going from animal-based to human insulin, the invention of insulin analogues with faster or longer action and the development of increasingly convenient delivery solutions. Each of these steps have helped ensure that people with diabetes have been able to live longer and have a better quality of life, but we also know that not all people with diabetes are in good glycemic control. We believe that our investigational weekly insulin icodec has the potential to offer a new standard of care in this space.”
From what the company has seen so far in trials with insulin icodec - pre-clinical and clinical trials until phase 2 - the weekly profile seems to offer good glucose-lowering with few instances of either too high or too low blood sugar: hyperglycemia and hypoglycemia.
In November 2020, results from a phase 2 study on icodec were published in the New England Journal of Medicine (NEJM).
“Phase 2 results showed that once-weekly treatment with insulin icodec was well-tolerated and had glucose-lowering efficacy and a safety profile similar to those of once-daily insulin glargine U100 in patients with type 2 diabetes.”
The weekly dosing regimen of insulin icodec will, if approved, offer greater convenience compared to daily injections, reducing the number of injections needed on a yearly basis from 365 to 52, said Rasmussen. “Our ambition is to confirm the observed profile in our clinical phase 3 program.”
Insulin icodec is now in phase 3 development, and includes people living with both Type 2 and Type 1 diabetes.
“We initiated the phase 3 program, ONWARDS, in 2020. It includes six clinical phase 3 studies, one of which is applying a pragmatic approach to resemble real-world usage more closely. With the pragmatic trial, we aim to show the benefits insulin icodec might offer in a setting reflecting real world clinical practice and patients will have fewer study visits than normally seen in clinical studies. The trial also implements a digital tool to support titration of insulin icodec.”
Regulatory pathway
All trials in the phase 3 program for insulin icodec will complete this year, he said. “We will prepare global regulatory submissions as fast as possible once we have the required data.”
Looking at additional market opportunities approval of Insulin icodec would bring to Novo Nordisk in terms of its diabetes portfolio, Rasmussen said the company has initiated a phase 3 program: IcoSema. That involves a fixed dose combination of insulin icodec and Novo Nordisk’s once-weekly GLP-1 receptor agonist semaglutide. The program, which is called COMBINE, is expected to complete during 2024.
“We already have marketed a once-daily product combining insulin and GLP-1 RA. The aim with a weekly offering like the currently investigational product IcoSema is to allow patients to simply take one weekly injection rather than the 28 weekly injections patients on a full daily basal-bolus regimen must take currently.”
