5:56 PM
Mar 07, 2019
 |  BC Innovations  |  Targets & Mechanisms

Oral insulin innovation

How preclinical technologies could make oral insulin cheap enough to compete

While clinical data suggest an oral insulin product may finally be within reach, the technology struggles to compete with injectables on price and efficacy. A handful of academics and companies are pushing preclinical innovation in formulation and device design, aiming to solve the commercial conundrum.

Despite numerous setbacks over at least 50 years, the allure of an oral insulin product that eliminates frequent injections and reduces the risk of dangerous hypoglycemic episodes has continued to spur research in the field.

While needle technology has improved, making injections less burdensome for patients, developers argue that an oral product would produce fewer side effects and provide an opportunity to start therapy earlier in Type II diabetes.

The challenge of orally delivering insulin -- or any biologic -- has always been bioavailability. The acidity in the stomach destroys proteins long before they reach the circulation.

Over the last decade, several companies have developed formulations that shield a portion of the peptides from stomach acid and promote their uptake in the intestines.

The problem is that although these modifications achieve bioavailability high enough to control glucose levels, it may not be high enough to achieve cost-effective dosing.

“The result of the oral delivery approaches in the clinic is that you get bioavailability in the 1% or sub 1% range. 99.5% of the drug is going to get destroyed, so if you’re trying to deliver 10 units of insulin orally, you would need to package 1,000 units into the pill,” said Mir Imran, chairman and CEO of oral biologics delivery company Rani Therapeutics LLC.

That’s a big problem for cost of goods, he said.

Imran is also managing director of InCube Ventures, which co-founded Rani with GV in 2012.

While most oral insulin developers are going after Type I and II diabetes, there’s no consensus as to whether an oral insulin should compete with basal insulins, which are long-acting, or prandial injectables, which are dosed at mealtimes.

Academic and industry labs have been advancing a range of technological solutions from nanoparticles to gastrointestinal injection devices (see Table: “Oral Insulin Technologies”).

The latest comes from Robert Langer’s lab at the Massachusetts Institute of Technology, which partnered with Novo Nordisk A/S to create a capsule that injects insulin into the stomach wall, decreasing the amount of protein required for oral delivery.

At least three other preclinical oral insulins have been reported, including Rani’s RaniPill GI injection platform, an oral nanoparticle technology also from Langer’s group, and an intestinal patch from a Harvard University team.

Table: Oral insulin technologies

Although subcutaneous insulin injections have been controlling blood glucose levels in diabetic patients for almost a century, an oral insulin could be a patient-preferred alternative with lower risk of hypoglycemia and weight gain, while enabling dosing earlier in the course of disease. The table includes select oral insulin candidates and platforms in...

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