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Amylin Pharmaceuticals, Inc. Message Board

  • imdocus imdocus Mar 9, 2002 12:50 AM Flag

    Competition GLP-1

    http://dailynews.yahoo.com/htx/hsn/20020308/hl/genetically_engineered_hormone_ma
    y_help_fight_diabetes_1.html


    Saturday March 09 12:03 AM EST

    Genetically Engineered Hormone May Help Fight Diabetes
    By Ed Edelson
    HealthScoutNews Reporter
    FRIDAY, March 8 (HealthScoutNews) -- Genetically engineered versions of a natural hormone hold promise as a treatment for severe cases of Type II diabetes, the kind that begins in midlife when the body's production of insulin falters.

    The hormone, glucagon-like peptide 1 (GLP-1), offered excellent control of blood sugar levels in a Danish trial, according to a new report in The Lancet. It also helped participants lose weight.

    Perhaps most important, GLP-1 appears to stimulate growth of beta cells, which produce insulin. It one day might help diabetics reduce their reliance on medication, says Dr. Jens Juul Holst, study author and a professor of medical physiology at the Panum Institute in Copenhagen.

    "There was a very significant effect in every one of the diabetes patients we looked at," Holst says.

    The trial included 20 patients with Type II diabetes. Half took a continuous infusion of GLP-1 for six weeks, while the other half received a placebo. Tests showed "a profound improvement of metabolic regulation during treatment" with GLP-1, Holst says, in part because the hormone increased the effectiveness of the body's limited production of insulin. The hormone converts sugar to energy in the body.

    GLP-1 can't be taken orally. In the Danish study, participants received the hormone by continuous infusion, using a miniature pump similar to that used for insulin therapy. The benefits of GLP-1 make that inconvenience worthwhile, Holst says.

    Restoragen Inc., a biotechnology company based in Lincoln, Neb., supplied the hormone for the Danish study. A multi-center U.S. trial that will include 100 participants at 25 to 40 sites has begun recruiting people, says Dr. Mario Ehlers, the company's senior vice president for business development.

    "We are focusing on the group of patients who have failed to control their condition using two first-line [drugs]," Ehlers says. Those patients must either go on to more advanced medications or start insulin injections.

    For those patients, GLP-1 "has the same inconvenience as insulin but is safer," Ehlers contends.

    "GLP-1 only stimulates insulin production when blood glucose levels are elevated, so there is a self-regulating mechanism," he says. By contrast, an insulin injection always reduces blood glucose levels, so there's a risk of too great a reduction, he says.

    Results of the U.S. trial will help Restoragen decide whether to move on to more advanced studies aimed at winning U.S. Food and Drug Administration approval of the hormone therapy. The company is seeking a partner because it doesn't have the money to test and market the product on its own, he says.

    Restoragen is in a race with two larger companies, including Eli Lilly & Co., which have their own versions of GLP-1. Those versions can be taken by injection, once or several times a day, rather than by continuous infusion, Ehlers says.

    The potential market is the 30 percent to 40 percent of people with Type II diabetes who either must take multiple oral drugs or have insulin injections, Ehlers says.

    If GLP-1 lives up to its early promise, it could be used to help treat people with Type I diabetes, in which there is no natural production of insulin, he says.

    "Because of its effect on beta cells, it could potentially restore some function in Type I diabetes," Ehlers explains.

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    • I am intense beleiver in exendin, but on what basis do you make the following statements

      <This stunning achievement (my opinion) has garnered intense interest from big pharma.>

      Just curious, if you know something that we dont, please share

    • saved many of yours and experts of your earlier, 1999, posts and still find them very educational as they were on target. Can you give us your opinion on how the next 3-5 years will play out?
      Thanks in advance

    • Indeed, both Lilly and Novo have had GLP-1 analog development programs going for years, trying to extend the in vivo half-life of GLP-1. You can see the success of their work thus far--nothing commercially approved.

      Grasp the magnitude of success that Amylin has exhibited thus far in this area. Literally coming from nowhere, the company has advanced exendin-4 into advanced stages of Phase 3 clinical testing in a relatively short period of time. This stunning achievement (my opinion) has garnered intense interest from big pharma.

    • Ah, the light that went on over my head has now lit over yours it appears. Lower HbA1c, regenerated beta cells, weight loss, LAR, the only thing the Exendin won't do if all these possibilities become reality is to help you pick the winning horse in the next race :-). But then again you might want to buy the racetrack.......

    • imdocus,

      restoragen research demonstrates that glp-1 has a huge effect - whopping significance levels with just 10 subjects in the experimental group. it also shows that glp-1 and presumably glp analogs, have clear stand-alone potential. what concerns me is that amln seems to be doing its phase 3 trials on exendin in combination with metformin and/or sulfanylureas. is this true, or are they also looking at exendin as stand-alone? if they get stuck with a combo-only label this could put them at a disadvantage against a drug that comes later with a stand-alone label, no?

      peter wolff

      • 2 Replies to peterwolff
      • Not close between exendin and GLP 1. Exendin appears to be much better. It is much better because it has a half-life in the human body of hours as compared to seconds for GLP 1. This makes GLP 1 therapy unfeasable other than in the form of continuous infusion. Attempts to make GLP 1 last longer have harmed its potency, making the dose size grow to very large levels. How large? Golf-ball size for GLP 1 versus a fleck of dandruff size for exendin. It is this very high potency combined with the long half-life that makes LAR exendin possible. The LAR version of GLP-1 would be about the size of 900 golf balls.
        Exendin is not now being tested on patients not on any oral medications because the target population for injectible drugs are those that are already on oral medications. If/when a non-injectible form of exendin is developed (it looks promising), then that version would make sense to test on diabetics who are not on oral medications.

      • I wouldn't worry about GLP-1 as competition for either Symlin (which is over 5X more powerful) or Exendin-4 (which is many times more powerful), simply because the half-life of GLP-1 is measured in minutes. Any GLP-1 injected into the body is very quickly metabolized. Some serious chemistry is needed before GLP-1 can be effective, EXCEPT via continuous infusion (and that means using a pump, like MDT-MNMD's $7000 insulin pump).

        In my view, the flurry of GLP-1 activity by Big Pharma can be interpreted as serious recognition of, and tribute to, AMLN's #1 and #2 drug candidates. AMLN's success will rock the world's Diabetes Boat. Watch it happen!

        Regards,

        war

    • >>>>Planning a trip to Eurrope ?.................<<<<

      As a matter of fact, I am!

    • What do you think the main advantages and disadvantages are for Exendin versus GLP-1? TIA

      • 1 Reply to Rincon_PR
      • Here's one advantage.

        From the GLP-1 article posted by imdocus: �GLP-1 can't be taken orally. In the Danish study, participants received the hormone by continuous infusion, using a miniature pump similar to that used for insulin therapy. The benefits of GLP-1 make that inconvenience worthwhile. . . . Restoragen is in a race with two larger companies, including Eli Lilly & Co., which have their own versions of GLP-1. Those versions can be taken by injection, once or several times a day, rather than by continuous infusion.�

        With Exendin (AC2993), the LAR version will require only one injection per month. And although AMLN is currently working only on the injectible form, they say this: �Using diabetic animal models, our research scientists have demonstrated that AC2993 is biologically active when administered via oral, sublingual, pulmonary, tracheal and nasal routes.�

    • Do you know who is the real competitor? Novo Nordisk A/S. and Scio Inc, see:
      http://www.sciosinc.com/scios/partners
      However the competitor may become the partner as someone said on the board.

      I have been really enjoied since the horse came on Feb. 12, 2002. HaHaHa!

      Have a nice weekend all!

    • Amylin says that Exendin is better than GLP-1 in that it has "a prolonged duration of action". I am not sure whether GLP-1 has the same gastric emptying benefit either. Here is AMLN's explanation:

      AC2993 (synthetic exendin-4)

      AC2993 (synthetic exendin-4) is a 39-amino acid peptide that exhibits several anti-diabetic actions of the mammalian hormone glucagon-like peptide (GLP-1). Unlike GLP-1, AC2993 has demonstrated to have a prolonged duration of action. In animal models, AC2993 has been shown to stimulate secretion of insulin in the presence of elevated blood glucose concentrations, but not during periods of low blood glucose concentrations (hypoglycemia). AC2993 has also been shown in animals to modulate gastric emptying to slow the entry of ingested nutrients into the bloodstream. It has also been demonstrated that chronic subcutaneous administration of AC2993 lessened food consumption in obese animals, leading to reduced body weight. Most importantly, in animal models of type 2 diabetes, AC2993 administration resulted in a lowering of blood glucose to near-normal concentrations. Using diabetic animal models, our research scientists have demonstrated that AC2993 is biologically active when administered via oral, sublingual, pulmonary, tracheal and nasal routes.

 

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