Israeli company testing insulin pill for diabetes treatment

Some people diagnosed with Type 2 diabetes can manage their disease with diet and exercise. Others must turn to insulin injections and other medical interventions to control their blood sugar levels. But diabetes is a progressive disease — even if medication isn’t needed at first, it may be needed over time, according to the American Diabetes Association (ADA).

And while most people with Type 2 diabetes would like to avoid insulin shots, they are a daily reality for many diabetics.

That’s where the promise of a new insulin pill comes in. Israeli company Oramed Pharmaceuticals Inc. just received an Israeli patent for an oral insulin capsule — what researchers have called “the holy grail” of diabetes treatment.

Diabetes is a metabolic disorder in which a person has high blood sugar, either due to the body not producing enough insulin (Type 1) or because the cells have developed a resistance to the body’s own insulin (Type 2). (Some women develop gestational diabetes during pregnancy and are at risk for Type 2 diabetes.) Left untreated, diabetes can damage nerves and blood vessels, and lead to complications such as heart disease and stroke. Other health problems can include kidney failure and vision loss. 

By 2030, there will be 366 million people worldwide affected by diabetes, the World Health Organization estimates. More than 25 million Americans currently have diabetes, and by 2034, this number could increase to 44 million, the ADA reports. Americans’ increasing obesity, sugar-laden diets and lack of exercise don’t help.

Injectable insulin was first given to people in 1922. Over the years, there have been numerous attempts to find a needle alternative, including an inhalable version. But various problems — including possible lung cancer and low profitability — forced inhalable insulin off the market, while research continues. Diabetics are hopeful the Food and Drug Administration (FDA) will approve Generex’s Oral-lyn inhalable, which uses a mist spray.

There are two main obstacles to creating an insulin pill: One is that insulin is a protein and, in a pill form, it would be broken down by enzymes in the stomach, much the way protein in food is, so insulin would never reach the bloodstream. The second is that the insulin molecule is too big to pass through the stomach or intestine wall.

“Imagine the intestine wall is a tennis net, and when you take a Tylenol, it’s like a small ball that passes through the net and reaches the bloodstream,” Oramed CEO Nadav Kidron said. “But if the ball is bigger than the hole in the wall, it will never reach the circulation and will have no effect,” he said.

He should know. His mother, Miriam Kidron, studied the disease for 35 years at Hadassah University Medical Center in Jerusalem. At 70, Kidron is a unique woman: the great-niece of Rabbi Abraham Kook, Israel’s first Ashkenazi chief rabbi, she went into the army and then got a master’s degree in pharmacology and a doctorate in biochemistry at Hebrew University. She researched diabetes at Hadassah while raising four children in Jerusalem (she now has 13 grandchildren). 

In 2006, she went to her son and said, “We have a breakthrough.”

Their new capsule has both an enteric coating, which prevents it from being dissolved in the stomach, and an anti-protease that prevents the pill from being dissolved by enzymes.

The technology, which received Israeli patent approval in May, has the potential to be used for flu vaccines, among other injectable medications.

A lawyer and MBA who worked with Israeli startups and the nonprofit world, Nadav Kidron, 38, and Miriam Kidron founded Oramed in 2006; Hadassah is a partner. The drug is entering phase 2 of its FDA trials, and Oramed hopes to have the capsule on the market by 2015 in the United States, and earlier in countries such as China and Russia.

Oramed is one of several companies in the race for the cure. Danish pharmaceutical giant Novo Nordisk is spending $2 billion on a pill, but its research in the United States is only at phase 1 of FDA trials. A handful of smaller companies searching for an insulin pill include Philadelphia’s Diasome Pharmaceuticals and Diabetology Ltd. in the United Kingdom.

But competition doesn’t bother Miriam Kidron. “Personally, at the end of the day, I am not afraid,” she said, noting that there will probably be a few options. “There is no one medication good for 100 percent of the population.”

Analysts believe the market for a successful pill is from $5 billion to $10 billion.

But it’s not the money that excites her. “Money is not my motivation. My children are all married [except Nadav], and I have what I need. Maybe if it was 50 years ago,” she mused.

What really drives the Jerusalem grandmother is simple: “I will be happy when people will have oral insulin.”

Pancreatic Cancer Studies Hopeful, But Funding Lags

It’s the fourth deadliest cancer, which will claim an estimated 34,000 lives this year. There are no surefire methods for prevention or early detection. And it resists treatments found to be effective in other cancers.

Until someone noteworthy like U.S. Supreme Court Justice Ruth Bader Ginsburg or actor Patrick Swayze is diagnosed with it, pancreatic cancer tends to keep a low profile.

Funding for pancreatic cancer research lags far behind that for breast or prostate cancer, even after the National Cancer Institute increased its spending by 20 percent last year. Despite the obstacles, local physicians and researchers are looking for better treatments and showing hints of optimism about potential progress against this disease, which strikes Jews with greater frequency than the general population.

The location of the pancreas — a pear-shaped gland tucked between the stomach and spine that aids in digestion and produces several hormones, including insulin — makes it difficult for physicians to see or feel masses during routine exams. Risk factors include a history of chronic pancreatitis, cigarette smoking, obesity or long-standing diabetes. And although the majority of cases are not hereditary, certain hereditary conditions (including Ashkenazic genetic mutations, like BRCA2) are associated with pancreatic cancer.

Pancreatic cancer frequently has no early symptoms, so the disease is typically diagnosed in advanced stages.

Attacking the Cancer

Physicians at UCLA participating in a Phase II clinical trial are testing a vaccine designed to stimulate the body’s immune response to cells that have undergone genetic changes associated with pancreatic cancer. The trial targets patients who have already undergone surgery.

“The idea is to teach the body to kill only the cells with the mutations,” said Dr. Edward Garon, an assistant professor of medicine with the UCLA David Geffen School of Medicine’s division of hematology/oncology. “We don’t know if it will be successful, but the hope is that we can reduce the likelihood of recurrent cancer.”

Another UCLA trial is looking to gene therapy to make tumors more susceptible to the effects of chemotherapy and radiation by rendering them vulnerable to inflammation. The hope for this Phase III trial is to more effectively kill cancer cells so patients with an advanced form of the disease can subsequently undergo surgery.

Researchers are also looking for substances to help boost the effectiveness of standard pancreatic cancer therapy, a drug called gemcitabine (marketed as Gemzar by Eli Lilly and Co.).

“This has been a frustrating area,” said Dr. Steven Miles, a medical oncologist at the Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center. “Gemcitabine itself was approved [by the FDA in 1997] after showing that patients live four months longer than the previous therapy. Despite numerous randomized trials testing different agents paired up with gemcitabine, only one showed positive results, and it only extended life by 14 days. Some patients had great response, and others showed none.”

Miles noted that treatment is becoming more individualized. Different chemotherapy drugs target different proteins associated with cancer. Since tests can now determine which proteins are elevated in an individual patient’s cancer, physicians can better predict which drugs would be most effective in that patient’s case.

The individualized approach is also driving research. “We are trying to identify genetic signatures that might help develop new drugs and targets,” said Dr. J. Randolph Hecht, professor of clinical medicine and director of the UCLA Gastrointestinal Oncology Program. “The one-size-fits-all approach to pancreatic cancer clearly has failed.”

Another focus of research involves analyzing how normal pancreas cells transform into cancerous ones.

“The idea is to attack the cancer before it starts, rather than after it has spread,” said Joseph Kim, assistant professor of surgery at City of Hope.

Improving Screening

UCLA is also participating in the Cancer of the Pancreas Screening Study (CAPS 3), which screens individuals who have multiple relatives with pancreatic cancer or who have gene mutations associated with the disease.

The study hopes to find proteins that indicate pancreatic tumor development and to develop an effective method of locating tiny pre-cancerous pancreatic lesions so they can be treated before developing into cancer.

Barriers to Progress

“We’re seeing more clinical trials than ever before. Still, we haven’t had a major breakthrough,” said Michelle Duff, director of research and scientific affairs for PanCAN (Pancreatic Cancer Action Network), a national organization promoting research, patient education and support.

Duff said pancreatic cancer is underfunded, noting that the National Cancer Institute, a co-sponsor of the CAPS 3 study, devoted $87 million for research into pancreatic cancer last year, compared to $237 million for colorectal cancer, $572 million for breast cancer, and $285 million for prostate cancer (the second, third and fifth highest mortality cancers, respectively).

UCLA’s Hecht noted that only 5 percent of all cancer patients nationwide are enrolled in clinical trials, and he would like to see that number increase.

“Clinical trials increase survival and quality of life,” he said. “They are the only way to improve the outcome of this terrible disease.”

Hope for the Future

While the statistics are bleak, the researchers interviewed remain optimistic.

“I strongly believe that with a strong research program, followed by well-conducted clinical studies, we will be able to make substantial progress in the treatment of pancreatic cancer,” UCLA’s Garon said.

“We don’t know where the next treatment advance might come from,” Cedars-Sinai’s Miles said. “Being alive with AIDS in August of 1995 versus September of 1995 meant the difference between death and survival. Because that’s when a new drug completely transformed treatment. The same thing could happen for pancreatic cancer.”

For more information about pancreatic cancer treatment and research, call PanCAN’s Patient and Liaison Services at (877) 272-6226 or visit