An insulin pill, long desired by
diabetes doctors and patients but abandoned as not physically viable,
could be available by the end of this decade as a tiny Israeli company
races a Danish pharmaceutical giant to be first with what could be a
multibillion-dollar product. http://www.dmgkd.com/story.php?title=truth-about-cellulite-2
In the pharma industry's equivalent
of a David and Goliath story, the companies at the forefront are Novo
Nordisk, the world's largest seller of insulin products with a market
value of about $74 billion, and Oramed Pharmaceuticals Inc, with a
market value of only $50 million and headquartered in Jerusalem, where
the biblical David held court.
The concept of oral insulin as a way
to relieve people with type 1 diabetes of several daily injections has
been around since the 1930s. It was left for dead because as a protein
composed of amino acids, insulin is destroyed by enzymes in the
digestive system before it can do any good.
http://keystonesearch.org/story.php?title=fat-loss-factor-review
While skepticism over a viable
insulin pill remains high, Novo and Oramed believe they have come up
with solutions that will allow enough insulin to survive the onslaught
of digestive juices.
If all goes well, Novo believes its oral insulin could be available by the end of this decade or early next decade.
Oramed's program is ahead of Novo's.
It has begun enrolling patients in Phase II, or midstage, clinical
trials, while Novo has yet to begin Phase II testing.
The brains behind Oramed's oral
insulin is the chief executive's mother, Miriam Kidron, who laid the
groundwork with years of diabetes research at Hadassah-Hebrew University
Medical Center. "She's the chief scientist. I just went for the ride to
do the business side," said Oramed CEO Nadav Kidron.
"My mother said it could be
commercial but Hadassah won't be able to fund it," Kidron recalled. "I
took the IP from Hadassah and started Oramed. Since then, we've been
moving it forward."
Regardless of who wins the race,
Kidron said, "there must be an oral insulin. This is going to be a huge
market." He sees the market potential to be at least $7 billion a year.
Novo said this week the global market for diabetes tablets could be worth more than $18 billion a year.
That is because the focus for oral
insulin has shifted to the ballooning health crisis of type 2 diabetes, a
progressive disease often caused by obesity. An estimated 90 to 95
percent of the more than 370 million people living with diabetes
worldwide suffer from type 2, according to the International Diabetes
Federation. It projects that could climb to 552 million by 2030.
GBI Research forecast the global market for type 2 diabetes treatments reaching nearly $40 billion by 2019.
"Even though there are other
anti-diabetic agents and more coming in, ultimately all (type 2)
patients with diabetes, if they live long enough, will need insulin,"
said Novo's Kurtzhals.
There is still a long way to go for
Nova or Oramed to receive regulatory approval. The companies must prove
the worth of their oral preparations with large clinical trials and
demonstrate no heart problems or other major side effects.
Other than injections, no other
insulin preparations have been shown to be satisfactorily safe and
effective, doctors said. Past failures of alternative delivery systems
include Pfizer Inc's abandonment in 2007 of its inhaled insulin product.
"I'm not going to hold my breath on
this one," said Dr. Robert Ratner, chief science and medical officer for
the American Diabetes Association (ADA).
"It would be an important
contribution to the therapeutic armamentarium. But there are still great
limitations in our ability to get the insulin absorbed and control how
much insulin gets absorbed," Ratner said.
Other treatments being tried include
nasal spray and a skin patch, which lack some of the potential
advantages of an oral insulin.
A MORE NATURAL APPROACH
Insulin injections were introduced
commercially as a life-saving treatment for diabetes in 1923 by Eli
Lilly and Co. Novo has also sold insulin products for some 90 years.
While insulin is naturally produced
in the pancreas and then goes to the liver, injected insulin circulates
throughout the body before it gets there. The main attractiveness of an
insulin pill, if it works, is that any absorbed insulin would go
directly to the liver from the digestive tract.
"It is a much more natural
physiological approach," said Dr. Joel Zonszein, director of the
Clinical Diabetes Center at Montefiore Medical Center in New York.
Some doctors believe high levels of insulin circulating through the rest of the body may increase health risks.
Since the digestive system can break
down insulin in a matter of seconds, both Novo and Oramed's approaches
for their insulin pills involve protective coatings and molecular tweaks
or added ingredients to help enough insulin be absorbed to provide
effective glycemic control. That involves giving large enough doses of
insulin so that some 90 percent can be destroyed without sacrificing
efficacy.
Novo believes it has designed a more
stable molecule than natural insulin that can slow the time of
degradation to minutes. "And if you can do that, maybe it's sufficient
time for absorption to take place," Kurtzhals said.
"Risk is still high for this type of
project. But the chance of success has gone up quite dramatically in
our own minds compared to what it was originally," he said.
Oramed has introduced a protease inhibitor and another tweak designed to protect and enhance absorption of its oral insulin.
Kidron sees oral insulin as an
opportunity to save billions of dollars in healthcare costs by helping
to delay the myriad complications associated with type 2 diabetes.
"If we give insulin earlier on,
we're going to give the pancreas a rest," Kidron explained. "We could
reduce the complications, such as blindness and amputations."
He likens earlier treatment with an
insulin pill to Pfizer's Lipitor, which became the most profitable drug
in history by preventing serious heart problems.
Dr. Jason Gaglia, a top researcher
at Harvard Medical School's Joslin Diabetes Center, said an oral insulin
could be used to better control overnight blood sugar.
"If you could give it in an oral
pill that is just hitting the liver, it would be wonderful," he said.
"If people take this pill at dinner time, they're not going to have this
excess glucose production overnight and it will be really good for
getting those morning blood sugars down."
INSULIN STIGMA
Persuading patients to take insulin
earlier in their disease could take some work, however. Some doctors now
see a stigma surrounding the need for insulin - rather than needles,
which have become much smaller and less painful - as a possible
impediment to its acceptance by those with type 2 diabetes.
Patients may see insulin as an
indication they are sicker than they perceive themselves to be, or
associate it with a relative who got insulin late in the disease only to
see their health deteriorate, doctors said.
"We need to do some education to
convince people that insulin is a therapy like any other and it's very
effective," said Dr. Elizabeth Seaquist, a member of the Endocrine
Society who is in line to become a future ADA president.
The riskiness of the project and the
number of years it will take to come to fruition is likely a reason
Oramed's market value remains relatively small. The shares are trading
for just over $6 and the CEO is the largest shareholder.
The company, which is also
developing oral versions of other injectable drugs, plans to take its
insulin through Phase II testing and then find a partner with deep
pockets to conduct large, expensive Phase III trials and market the
drug.
Kidron see no shortage of potential
partners among Japanese drugmakers, U.S. companies with diabetes sales
forces, or even Novo Nordisk - a scenario in which Goliath could simply
buy David's slingshot.
"Novo is in a different league from anyone else out there," Kidron says with admiration. "I look up to them."
