TOKYO – Rani Therapeutics LLC is working on a delivery system for insulin that could provide relief for millions of people who must undergo regular painful injections to deal with conditions such as diabetes, rheumatoid arthritis, osteoporosis and multiple sclerosis.

Rani's chairman and CEO, Mir Imran, spent years trying to find a way to administer injectable drugs orally. He found inspiration in the unlikeliest of places: a glass of Alka-Seltzer.

The challenge is that the digestive juices in the stomach destroy the proteins that make up large molecules such as insulin, rendering them ineffective before they enter the bloodstream. So Rani created a capsule coated with an ingestible polymer, using carbon dioxide to expand the capsule and then using tiny hollow sugar needles to push the medication into the wall of the intestine, where it can then naturally enter the bloodstream.

"After I got the initial concept of injecting drugs in the intestinal wall, it took nearly three years to perfect the capsule technology," Imran said. "We had to overcome many challenges in material science and the manufacturing process development."

Imran is an entrepreneur and innovator who has founded more than 20 life sciences companies and is the founder of the Silicon Valley search lab and business incubator Incube Labs LLC, of San Jose, Calif. He owns more than 300 patents and helped develop the first implantable cardioverter defibrillator to correct irregular heartbeats. Google is an investor in Incube.

Preclinical results in animals have shown that the capsule is effective to deliver drugs based on proteins, antibodies and even insoluble small molecules. Clinical trials on people have not started yet.

"In all the preclinical testing that has been done with the capsule with various molecules such as insulin, Humira, etc., we have not seen any adverse effects caused by the delivery platform," Imran said.

Humira (adalimumab) is an anti-TNF antibody drug marketed by Abbvie Inc.

Rani plans to start human trials next year and to have the delivery mechanism available in about three years, but that timing is dependent on Rani's drug and pharma partners.

"Our capsule has bioavailability that is close to 90-plus percent, which is as high as a drug's absorption when administered using a syringe," a Rani spokesperson said.

Imran claimed "the new capsule also has the potential to transform the entire biotech industry, especially the insulin market."

"The impact on type 1 diabetic patients could be very significant," he said. "Type 1 diabetics are totally reliant on insulin because their pancreas has stopped working. Currently, the market for basal insulin is over $10 billion annually. Rani Basal Insulin could take a big portion of this market and expand it quite significantly."

The three biggest markets for insulin are currently the U.S., Europe and Japan. Nearly 3 million people in the U.S. have type 1 diabetes, and there are nearly 1 million sufferers in Japan.

Rani aims to form partnerships with pharma companies in Asia, North America and Europe as it searches for the massive financing needed to manufacture the millions of capsules Imran anticipates will be needed. With that as a goal, the U.S.-based medtech entrepreneur visited Japan early this month. One top multinational pharmaceutical company has signed a confidential agreement with Rani, he said.

"We are now seeing simultaneous development in these three regions, because of the opportunity cost of a delay in any of the regions," said Reed Maurer, a Japanese pharma industry watcher and president of International Alliances Ltd.

"Those with the disease learn early on to cultivate a healthy distrust for announcements of 'cures' or 'breakthroughs,'" said Harry Mahaffrey, a diabetic activist and graduate student at Purdue University who was diagnosed with diabetes at age 12. "A cure for diabetes has been 'five years away' since I was diagnosed,"

Rani's capsule delivery system is not a cure but a management system that can have a direct impact on patients' lives because constant self-injections have consequences like bruising, hardening of the fat at frequently used injection sites and even infections.

"As a diabetic, I have faith in the biotech industry," Mahaffrey said. "After all, they've kept me going this far. "

Biotech and medtech companies are working on a number of alternatives to injections. On June 27, the FDA approved inhaled insulin product Afrezza developed by Mannkind Corp. to improve glycemic control in adults with type 1 and type 2 diabetes. Afrezza is not a substitute for long-acting insulin and needs to be used in combination in patients with type 1 diabetes. (See BioWorld Today, June 30, 2014.)

There are still some unknown factors regarding possible adverse effects of Afrezza, which should not be used by patients with asthma and chronic obstructive pulmonary disease; nor is it recommended for the treatment of diabetic keloacidosis or in patients who have chronic lung diseases. The FDA has required four postmarketing studies for Afrezza.

Developing a marketable oral delivery system would be a game-changer, which has led to a number of attempts over the years to perfect such a method that can compete with injectable delivery in terms of bioavailability. And Rani is not alone.

Empisphere Technologies Inc., a small New York pharmaceutical firm, also is developing a pill coated with a special molecule that allows the insulin to penetrate the wall of the intestine and enter the bloodstream. Emisphere has partnered with Novo Nordisk A/S to develop and commercialize the oral delivery of Novo's insulin compounds, and the project is in the preclinical stage.

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