Biotech Values

[DewDiligence]

>The spokeman, I mean spokes lizard for byetta?<

Correct!

[c/o 'bridgeofsighs' on the SRDX board]

http://www.reviewjournal.com/lvrj_home/2005/Nov-03-Thu-2005/living/4019920.html

>>
Lizard's venom a saving grace

Nov. 03, 2005
Las Vegas Review-Journal

Gila monster helping those with Type 2 diabetes feel better

Some diabetes patients are startled when Dr. Brian Berelowitz says their new medicine will require them to stick a lizard in the blender twice a day.

He's joking. The new drug, intended for Type 2 diabetics, derives from venom in the saliva of a Gila monster, a lizard that is native to the U.S. Southwest. But the compound has been synthesized in the lab, so put away the blender.

Going by the brand name Byetta, the drug -- whose scientific name is exenatide -- gained U.S. Food and Drug Administration approval in April, and came out in June.

It controls Type 2 diabetes by boosting the production of insulin, which helps the body process blood sugar. When blood sugar, which is largely glucose, is smoothly processed, body tissues pluck it from the bloodstream, either to power their cells or to store for later use. When sugar simply collects in the blood to excess levels -- a condition called hyperglycemia -- it can damage the kidneys, liver and eyes.

Byetta cannot help people with Type 1 diabetes, because the pancreas cells that produce insulin have been destroyed, not just impaired, as in Type 2.

The new drug is injected by a "pen" system. Berelowitz says many diabetics who claim to be afraid of needles rapidly overcome their fear when they learn Byetta will help them drop pounds, too.

"They feel better. They lose weight. They lose their sugar craving. Sugars don't go up after meals. They get less sleepy, have more energy. Sometimes we're able to decrease their other drugs, (which have) side effects." That is a litany of Byetta praises from Berelowitz, a Summerlin-based endocrinologist. He estimates he already has 100 patients taking it. He also lectures to groups of physicians on the new drug.

"It's the most intelligent diabetes drug," Berelowitz adds, by which he means the drug tackles diabetes on several fronts.

It improves a patient's sense of fullness after eating, so he or she is less apt to overeat or binge on sweets. It slows emptying of the stomach, which inhibits a rapid rise in blood sugar after a meal. "Post-meal blood sugar ... is a huge bugaboo," the endocrinologist notes.

Byetta also seems to improve a diabetic's regulation of glucagon, a hormone that works in opposition to insulin. And Byetta seems to restore the beta cells that produce insulin; in poorly controlled Type 2 diabetes, the pancreas cells reach an overworked state called beta-cell exhaustion, and sometimes die.

Byetta triggers insulin release, but also shuts off production when it senses blood sugar has dropped. It doesn't operate "blindly," as some diabetes drugs act. It is therefore less likely for a patient on Byetta to accidentally drop his or her blood sugar too low -- a condition called hypoglycemia, which is also dangerous.

"This is like a smart bomb for diabetes," Dr. David Kendall of the American Diabetes Center in Minnesota told the San Diego Union-Tribune in spring. On April 29, the newspaper was reporting on the role of a small San Diego biotechnology firm, Amylin Pharmaceuticals, in bringing Byetta to market. Kendall was chief investigator for Amylin's human trial of the drug.

Business analysts predict Byetta will be a financial blockbuster, both because of the prevalence of diabetes in this country and the drug's effectiveness, according to the Union-Tribune.

Byetta is an incretin-mimetic. That means it mimics a human hormone that sends signals to the pancreas to start producing insulin when food has arrived in the gut, needing digestion. But Byetta -- a synthesized version of Gila monster hormone -- is superior to synthetic versions of the actual human hormone. The human hormone breaks down so rapidly that a diabetic would have to administer it many times a day, for round-the-clock coverage. But the synthetic lizard hormone lasts long enough that Type 2 diabetics need only two doses a day.

It's not coincidence that the Gila monster hormone breaks down slowly. That features perfectly serves the shy reptile. It rarely eats, because it spends 95 percent of its time hiding in burrows, according to Alex Heindl, a herpetologist, which means he is a reptile scientist. His duties at the Marjorie Barrick Museum of Natural History at the University of Nevada, Las Vegas include caring for two live Gila monsters.

"Gila monsters are considered to have one of the most efficient digestive systems known," Heindl says. The desert animal's digestive system "allows it to very easily subsist for up to a year on three or four good meals."

A Gila monster feeds on snake eggs, rodents and other small prey. Its venom probably acts as a digestive enzyme, according to Heindl. The lizard doesn't inject its venom, but mixes it into its saliva as it chomps down on prey, which is killed by the force of the animal's strong jaws.

The lizard also uses its venom as a defense mechanism against "anything that tries to mess with it, such as coyotes, badgers, probably birds of prey (and) us," Heindl says. But Gila monsters are so shy that, herpetologists joke, "anybody who gets bitten by a Gila monster probably deserves it," the herpetologist adds.

The Food and Drug Administration has approved use of Byetta when taken with certain oral diabetes medicines, either metformin or sulfonylureas. Its approval does not cover taking Byetta alone to treat diabetes, nor taking Byetta with insulin injections.

Nausea is a common side effect when a patient starts on Byetta, so the initial dose is often lower. Then it is raised when nausea subsides, usually in six months. But weight loss continues in patients, even after 84 weeks on the drug, studies show. That is strong evidence that losing weight while on Byetta is not because of a loss of appetite from initial nausea, Berelowitz points out.
<<