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Oral insulin clinical trial underway at Flint research center

  • Flint-based AA Medical Research Center is one of 24 sites in 13 states where oral insulin capsule is being tested
  • Oral insulin could potentially replace daily injections that many patients don’t want to do
  • Nearly 1 million adults in Michigan have diabetes, with 2.7 million showing prediabetic symptoms
 
AA Medical Research Center
Ahmed Arif, M.D.

The race is on to perfect a capsule to control type 2 diabetes — and a Michigan research clinic is playing a part.

Experts said oral insulin in capsule form holds the best chance for people with diabetes to improve treatment compliance with their chronic disease, which is the seventh-leading cause of death in the U.S. This is because an estimated 25 percent of the 870,000 people in Michigan and more than 30 million nationally diagnosed with diabetes don’t take their daily injection of insulin either because it is too expensive, it is unpleasant or they fear needles.

“It’s a big problem. Taking insulin orally could increase compliance because if they have a choice between a pill or a shot, they will take the pill,” said Ahmed Arif, M.D., owner, director and principal investigator at AA Medical Research Center, a multi-specialty clinical research facility in Flint where the oral insulin drug is being tested.

Several pharmaceutical companies such as insulin-maker Novo Nordisk and research universities, including Massachusetts Institute of Technology and Harvard University, have been testing a variety of approaches for oral insulin over the past several years. Drug giant Pfizer invested millions into oral insulin research only to come up empty in 2007.

The chief problem with making oral insulin work is getting the insulin-filled capsule past the stomach, where the pills are destroyed by acid.

“Oramed has a special delivery system to protect the insulin, get it past the stomach to the liver where it can work,” said Arif, an internist and pediatrician. AAMRC is one of 24 research sites in 13 states, and the only one in the Midwest, participating in a phase two clinical trial sponsored by New York-based Oramed Pharmaceuticals (NASDAQ/TASE: ORMP), a small drug company backed by venture capitalists and Chinese investors. “There is a clear race to getting the first technology for oral insulin,” said Oramed CEO Nadav Kidron. “Other companies are working on different products. Our formulation enables the insulin to get directly to the liver. This is the natural way: from the pancreas to the liver.” In 2006, Kidron co-founded Oramed with his mother, Miriam Kidron, a former researcher at Hadassah-Hebrew University Medical Center in Jerusalem and the company’s chief scientific officer. She developed the technology in an effort to help her husband treat his diabetes. “My father suffered from diabetes, and it was my mother’s mission to find an alternative way to deliver insulin,” Kidron said. “When she told me that they had a breakthrough that could help millions of people around the world, that’s when I knew I had to make it a reality.” Oramed has only 15 full-time employees, but Kidron said he outsources most of the work. It has raised capital from several sources, including Regals Capital Management in New York. Oramed also has signed a licensing deal with HTIT, a Chinese pharmaceutical company, that also has invested $33 million in hopes of bringing oral insulin to China. Worldwide, diabetes also is a growing concern with studies showing some 425 million adults have diabetes globally. That number is expected to reach 629 million by 2045. Kidron said oral insulin also could be more effective than current treatments. For example, insulin is typically injected directly into the bloodstream, but only a fraction reaches the liver, often causing excess sugar to be stored in fat and muscle, which can result in weight gain. With Oramed’s proprietary “protein oral delivery” platform, the active insulin is protected in a special capsule as it travels through the stomach and into the intestine, and its absorption is increased by an enhancer supplement along the intestinal wall, Kidron said. “By preventing protein-drug breakdown in the gastrointestinal tract and promoting its crossing the small intestine, this breakthrough solution brings oral protein-drug delivery significantly closer to a reality,” Kidron said. “The result is better glucose control, reduced hyper and hypoglycemia, and potentially less weight gain — and treatment can begin earlier, improving outcomes.” In the past year of the study, 24 research sites have enrolled about 300 people in the placebo-controlled, randomized phase 2b study. More than 80 percent, 237, have completed the trial. Drugs that show they work in phase 2b studies then can go on to major studies in thousands of patients that can lead to drug approval. The goal is to show the effectiveness and safety of “ORMD-0801,” as the drug is currently named, in type 2 diabetes patients who have inadequate blood sugar control. If the drug can lower average blood sugar levels over three months, the test would succeed, Kidron said. Kidron said the multi-site study will be completed later this year. He said the data will be submitted to the FDA, which could approve the start of expanded testing of the drug. If all goes well, oral insulin could be on the market in two or three years. “It is going very well. The most important thing with the drug is that it works, and it is safe. How well it is working, we will find out in the next three or four months when we unblind the study and find out,” Kidron said. While Arif doesn’t know which of his nine patients are being treated with oral insulin or the placebo, he said: “My gut feeling is it will work.” Ajaz Banka, M.D., an endocrinologist at the Beaumont Endocrine Center in Beverly Hills, said the clinical trial is an important step forward in diabetes management. “It could be a game changer. There is a need for something like this because we have 10 percent of the population in Michigan affected by diabetes,” he said. Banka said many patients diagnosed with diabetes don’t want to start insulin treatment right away. “They worry about it. It is about four shots per day. Cost is a huge issue. There is a benefit and insulin can prevent a lot of problems,” he said. But Banka said the big challenge is developing a pill that bypasses the stomach and gastrointestinal tract where it is broken down.
“Insulin is a protein. We digest protein in the stomach. You need to bypass that before it is absorbed and broken down,” Banka said. “Then there is the question of how long it stays in the system. Is it short or long acting?”
Why Flint research facility?

Oramed selected AAMRC because metro Detroit has a high percentage of people with diabetes and because the company has worked with the Flint center before and it has a good reputation, Kidron said. About 10.6 percent of the population of metro Detroit has diabetes, compared with 9.3 percent nationally.

AAMRC is part of Arif’s internal medicine and pediatrics practice where he also sees patients. The 17-year-old research center has conducted more than 100 clinical trials on conditions including type 2 diabetes, chronic kidney disease, hypertension, heart failure, rheumatoid arthritis, osteoarthritis and asthma, mostly pharmacy company-sponsored research, with 14 trials ongoing, including the Oramed study.

Arif said most of his research subjects come through his office, although he lists the trials on his website. The FDA doesn’t allow him to advertise for human subjects in research trials.

So far, seven patients have already completed the 90-day tests. Two more patients are undergoing the tests. “Not everybody qualifies for the study. We had 15 or 16 volunteer. We are looking for patients who have poorly controlled diabetes and are not already on insulin,” Arif said.

The nine people going through the testing in Flint must be 18 years or older, have type 2 diabetes, an HbA1C (blood sugar) count of more than 7.5 percent and a body mass index of less than 40 (more than 40 is considered obese). People also must be taking metformin, which is a drug that helps lower blood sugar levels, allowing insulin to work better. About 25 percent of patients in the trial received a placebo.

Nearly 900,000 people in Michigan have diabetes with an estimated 2.7 million more with prediabetes, said Michigan Department of Health and Human Services. In 2018, these conditions will cost Michigan an estimated $9.7 billion. An A1C above 6.5 percent is considered positive for diabetes. A normal blood sugar level is considered below 4.6 percent.

Type 2 diabetes, sometimes called ‘adult-onset’ diabetes, is the most common form of the condition, accounting for up to 95 percent of all Americans diagnosed with this metabolic disorder. In type 1 diabetes, which is often hereditary and non-preventable, the immune system wrongly attacks and damages the cells of the pancreas that produce insulin, a hormone that is key to regulating blood sugar levels.

In type 2 diabetes, the insulin the body produces doesn’t function as effectively as it should, hence it is also sometimes called “insulin resistance.”

Diabetes is characterized by high blood sugar, or hyperglycemia. When the body does not produce enough insulin, a hormone that transports sugar from the blood into the cells for energy, blood sugar levels rise, causing the conditions for diabetes. Complications from the disease includes blindness, kidney failure, stroke and heart attack.

Link: https://www.crainsdetroit.com/health-care/oral-insulin-clinical-trial-underway-flint-research-center