An insulin pill that could make you drop the needle

In Manesar, Haryana, better known as an automobile hub, researchers in white biosafety suits pace a room lined with shiny steel fermenters brewing a secret formulation for managing diabetes. The condition which afflicts one in 11 worldwide, according to the International Diabetes Foundation, is a complex disorder that results from the body unable to properly manage insulin.

SCRIPTING THE FUTURE: “Given the ‘psychological discomfort’ that people have with injections, a pill could be a game changer.” Picture shows a fermentation unit at Premas used for making oral insulin components. — PHOTO: V. SUDERSHAN

This hormone, made in the liver, is necessary to ensure that cells of the body get adequate glucose and hence energy to survive.

Most diabetics have inadequate insulin and the best fix now — along with a range of pills and depending on the severity of the condition — is to rely on a regimen of jabbing oneself with the hormone. Though the discovery of insulin has yielded Nobel Prizes, it’s so far been an unsuccessful 90-year quest of finding a way to administer insulin orally. That’s because insulin is rapidly degraded in the body and pills, because they rest in the stomach, are quickly corroded by the acidic environment of the intestines.

Premas Biotech, the biotechnology company hosting the fermenters, is part of a trans-national partnership of organisations spanning Israel, India and China that may just have gotten the furthest to cracking this puzzle.

On July 28, the Jerusalem-based Oramed Pharmaceuticals said it had encouraging results from limited, or phase 2 trials on 180 diabetics. That puts it ahead of two other companies, Bengaluru-based Biocon, which also has a test oral insulin pill (Tregopill) that will soon begin human trials, and Danish pharma major Novo Nordisk, the global leader in insulin therapy. On August 5, the Danish firm said it had made “good progress” with Phase 2a trials on a potential oral insulin pill.

How it works
Oramed’s pill consists of insulin coated in a capsule that manages to survive the hostile environment of the stomach. Through “absorption enhancers”, the company claims to ensure that the insulin stays long enough in the small intestine and enough of it gets through to keep glucose levels down — the primary objective of all insulin therapy.

Moreover, Oramed said the insulin in this case wasn’t released in the blood and instead went to the liver simulating the way nature managed insulin in non-diabetics. “Type 2 diabetic patients are insulin resistant, meaning they require more insulin to carry out the work of a non-diabetic patient. This puts tremendous strain on the beta cells (which produce insulin) in the pancreases,” Josh Hexter, Chief Operating Officer, Oramed told The Hindu in an e-mail. “It has been shown that incorporating insulin earlier on in the therapeutic paradigm is helpful in pushing off the effects of type 2 diabetes. This (among other areas) is where Oramed can play a huge role in bringing massive value to the diabetes patient population.”

Premas’ role lies in devising a process to commercially produce this formulation by raising it a hundred-fold while maintaining quality and reducing cost. Oramed has already licensed out its technology to a Chinese firm. Premas has been tasked with setting up processing facilities in China.

“In particular, the focus on shaving off costs (while keeping quality) has highlighted Premas’s strengths in this partnership,” said Mr. Hexter. “Over the years we have increased our relationship from a pure pay to work which relates to commercial scale up.”

Premas’s Executive Director, Prabuddha Kundu, says that there were “major innovations in process” that the company had brought in. Unlike regular pills that were salts of chemicals, insulin and insulin-based products (or large molecules as they are called) are sensitive to contamination. “There is a bit of (scientific) dark arts, trade secrets involved in being able [to] scale up production,” says Mr. Kundu. “That’s why we’ve always preferred to fly under the radar.”

Measured reactions
Independent experts told The Hindu that promising as Oramed’s trial results appeared, a solution for oral insulin was still far from the horizon. On the other hand, irrespective of whether Oramed’s pill advanced, it was a significant step ahead for Premas because it showed that Indian companies were sophisticated enough to be involved in manufacturing complex molecules. “That an Indian lab may be involved in large-scale production is significant,” says Dr. Ganapathi Bantwal, endocrinologist and professor, St. John’s Medical College, Bangalore, “but the pill releases too little insulin.” In his opinion, at least 30 per cent more insulin was required to be available to the body for the Oramed pill to be even comparable to the current class of injectible medications. But given the “psychological discomfort” that people had with injections, a pill could be a game changer.

Diabetician Anoop Misra, Executive Chairman at Fortis C-DOC, too was sceptical given the history of failure to deliver insulin through means that avoided injections. He cited the withdrawal of Exubera — an inhalable version of insulin — a decade ago as a prime example of the challenges that Oramed faced. “Nearly 30 per cent of India’s diabetics use insulin and so an effective pill would be useful. Also there are several other alternative, non-insulin-based therapies available that are equally competitive. It’s not an easy road.”

Mr. Hexter adds that the company, which is very keen on the Indian market and will be attempting larger Phase 3 trials in 2017, sees its pill as a useful “value add” to the stages when diabetes would progressively worsen in people.