| To: Tadsamillionaire who wrote (229) | 12/23/2004 1:08:37 PM | | From: tuck | | | | >>VALENCIA, Calif., Dec. 22 /PRNewswire-FirstCall/ -- MannKind Corporation (Nasdaq: MNKD - News) released summary information today on results from its US-based, late Phase 2 clinical study of Technosphere® Insulin, a pulmonary insulin formulation delivered via its proprietary inhaler to patients with diabetes mellitus. The MannKind pulmonary insulin system rapidly delivers regular human insulin to the bloodstream in a manner that approximates the first phase insulin release spike by the pancreas that occurs almost immediately after the start of a meal in normal, healthy individuals but is lost in patients who develop diabetes. This spike plays an important role in glucose control by signaling the liver to stop releasing glucose into the bloodstream while glucose is being ingested from a meal.
The double-blind, placebo-controlled study was conducted at 21 sites in the United States. Patients who participated in the study were experiencing inadequate control of diabetes determined on the basis of HbA1c results (a measure of glucose control over the preceding three to four months) obtained at the time of screening. All patients received basic diabetes education and performed regular monitoring of blood glucose levels at home prior to randomization. A total of 123 patients (41 women and 82 men) were randomized into either a group that inhaled Technosphere Insulin (doses containing 6 to 48 units of insulin) or Technosphere placebo, in both cases at mealtimes. One hundred seven patients completed the full 12 weeks of treatment with blinded study agents.
Patients that constituted the primary efficacy population (n=90) had a mean HbA1c level of 7.74% at baseline with a range of 6.6% to 10.5%. As part of the study analysis plan, these patients were evaluated in two groups: those with moderately severe elevations of HbA1c levels at baseline of 8.0% and above (values identified by the American Diabetes Association as requiring definitive therapeutic intervention to minimize complications) and those with mild- to moderate elevations of HbA1c levels at baseline ranging from 6.6% to 7.9%.
Patients with moderately severe elevations of HbA1c levels at baseline (n=35; mean HbA1c 8.72%; range 8.0% to 10.5%), who were treated with Technosphere Insulin, experienced a mean reduction of 1.37 percentage points by the end of 12 weeks of treatment. The difference in reduction of HbA1c levels between the Technosphere Insulin and the placebo treatment groups was highly statistically significant (p=0.0007) in favor of Technosphere Insulin.
Patients with mild to moderate elevations of HbA1c levels at baseline (n=55; mean HbA1c 7.18%; range 6.6% to 7.9%), who were treated with Technosphere Insulin, experienced a mean reduction of 0.43 percentage points by the end of 12 weeks of treatment. The difference in reduction of HbA1c levels between the Technosphere Insulin and the placebo treatment groups was statistically significant (p=0.0447) in favor of Technosphere Insulin.
Overall, in the primary efficacy population, there was a highly statistically significant difference between the two treatment groups (in favor of the Technosphere Insulin group) with respect to the proportion of patients who achieved a reduction in HbA1c levels by the goal of at least 0.6 percentage points (chi-square; p=0.0052). Approximately four times as many patients in the Technosphere Insulin-treated group achieved a final HbA1c level of 6.5% or less as compared to the placebo-treated group.
There were no serious adverse events that were related to the use of the study drug. No episodes of severe hypoglycemia occurred in any of the patients treated with Technosphere Insulin. Pulmonary function was assessed by DLco measurements, FVC and FEV1 rates, and there was no clinically significant difference between the 12-week test results and baseline values in the patient group receiving Technosphere Insulin. Importantly, there was also no evidence of treatment-induced insulin antibodies occurring in patients treated with Technosphere Insulin.
Dr. Wendell Cheatham, Corporate Vice President and Chief Medical Officer of MannKind, commented, "This study indicates that Technosphere Insulin can effectively lower blood glucose levels in patients with type 2 diabetes who previously were experiencing inadequate control of their disease. The typical risks of frequent or severe hypoglycemia associated with insulin therapy appear to be minimal with Technosphere Insulin, giving it a potentially significant safety advantage over other therapies."
Alfred Mann, Chairman and Chief Executive Officer of MannKind, stated further, "In our earlier clinical studies, we observed that the kinetic profile of Technosphere Insulin approximates the first phase insulin release spike of normal, healthy individuals. With these latest observations of no increases in antibodies, no clinically significant changes in pulmonary function and no episodes of severe hypoglycemia in patients treated with Technosphere Insulin, we continue to be optimistic regarding the future of Technosphere Insulin. We are now preparing to submit these results to the United States Food and Drug Administration. In the meantime, we have initiated our first Phase 3 clinical trial in Europe, enrolling patients this week. We are pleased that the Company continues to achieve its intended milestones on or ahead of schedule."<<
Hmmm. No antibdies is good, beats competing inhalables; but otherwise, results are just like everyone else's, maybe even a little inferior. And this trial compares to a technosphere placebo, not to a s.c. insulin cohort. I assume they'll have to use a more robust comparison in PIII, but no details of that trial are given. Hmmm. As to pulmonary function, they deviate from using statistical significance and tlak of clinical significance. Hmmm.
Cheers, Tuck |
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| To: tuck who wrote (230) | 1/7/2005 11:20:43 AM | | From: rkrw | | | | I think the differentiator is going to be the device. If the first asthma albuterol device was a ntkr inhaler (looks like a bong but I don't think could work as a dual purpose device :-) and the next one out was a standard MDI puffer, which would win? So I think in the long run nktr will need a small device to compete. And the ardm device may not be much better, long run. alks/lly could be a darkhorse--very small device supposedly. I also wouldn't ignore mnkd, their ceo is a diabetes legend (founded Minimed). So call it a long term, 5 year type of prediction.
Alkermes Announces Lilly Decision to Proceed with Late-Stage Clinical Development Program for Inhaled Insulin
Tuesday, August 10, 2004
-- Cambridge, MA, August 10, 2004 -- Alkermes, Inc. (Nasdaq: ALKS) announced today that Eli Lilly and Company (“Lilly”) has made a positive product decision and will proceed with significant investment for the further development of an inhaled formulation of insulin. The decision follows the successful execution of several critical steps: the completion and analysis of data from a Phase 2 study; the achievement of commercial manufacturing powder production scale-up; and the development and testing of the commercial pulmonary insulin inhaler system. Development activities will include both clinical trials and additional manufacturing activities for the inhaler system and the production facility.
A recently completed Phase 2 clinical trial for inhaled insulin using Alkermes’ AIR® technology showed that patients with type 1 diabetes achieved glycemic control levels similar to injected insulin. The trial was a multi-center, cross-over design study with 120 patients with type 1 diabetes receiving an inhaled formulation of insulin using AIR technology for a three-month period. Inhaled insulin had a rapid onset of action and was well tolerated with adverse events similar in both treatment arms.
“We’re delighted that the strength of the clinical data and our achievement of commercialization milestones provided the basis of the decision by Lilly to move forward with further development for inhaled insulin,” said Elliot Ehrich, M.D., Chief Medical Officer at Alkermes. “We look forward to initiating additional clinical studies that will bring us another step closer to developing an important new treatment for the growing number of people living with diabetes.”
The inhaled insulin delivery system is based on Alkermes’ AIR pulmonary drug delivery technology, which uses a small, easy-to-use, inhaler designed to provide drug delivery for a wide range of drug doses. Alkermes and Lilly have collaborated on the inhaled insulin program since 2001 to develop an innovative treatment option for people with diabetes.
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| To: rkrw who wrote (233) | 2/6/2005 2:20:24 AM | | From: tuck | | | | [Compliance with inhaled insulin treatment using the AERx]
>>Diabetes Technol Ther. 2004 Dec;6(6):800-7.
Compliance with inhaled insulin treatment using the AERx iDMS Insulin Diabetes Management System.
Cramer JA, Okikawa J, Bellaire S, Clauson P.
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06516-2770, USA. Joyce.Cramer@yale.edu
OBJECTIVE: The AERx Insulin Diabetes Management System [AERx iDMS, jointly developed by Novo Nordisk (Bagsvaerd, Denmark) and Aradigm Corp. (Hayward, CA)] provides insulin by pulmonary administration. This investigation was designed as a pilot trial to demonstrate the ability of patients to use the electronic device to deliver mealtime inhaled insulin doses and explore the impact on compliance. METHODS: AERx iDMS was evaluated in a substudy of a 12-week, multicenter open trial by adult patients with type 2 diabetes previously on any insulin regimen. The device was used for dosing fast-acting human insulin immediately before main meals, in combination with bedtime NPH insulin. The AERx iDMS device recorded the date and time of each insulin inhalation, insulin units used, and inhalation technique during aerosol delivery. Compliance was defined as the percentage of prescribed doses taken during the treatment period, dose timing, and the efficiency of dosing technique. RESULTS: Insulin dosing for 49 patients (age 59.1 +/- 7.7 years) using AERx iDMS was monitored for 78.9 +/- 10 days (range, 41-94 days) with 226 +/- 35 doses (range, 122-272 doses). Patients inhaled on average 2.9 +/- 0.3 doses of insulin daily, taking an average of 11.8 +/- 5.6 units per dose. Compliance with the prescribed regimen was 94.3 +/- 9.1% (range, 45-100%). Overall, 4.2 +/- 9.5% of prescribed doses were omitted. Hemoglobin A1c decreased 0.77 +/- 0.96% from baseline to the end of the study. Inhalation technique was excellent, with 97% of patients experiencing fewer than five inadequate doses. CONCLUSIONS: Excellent compliance with AERx iDMS dosing, timing, and inhalation technique showed that the device was well accepted by patients. The electronic monitoring feature could be used as an educational tool to help patients and clinicians manage insulin dosing.<<
I think we've seen similar data in the past, so big sarcastic whoop, I guess, especially considering the events of the past year. Wonder what Novo has found? One almost wonders if they bought the program to bury the embarrassment. They had said the expected to be finished with their analysis of the stopped trial months ago, but I've seen nada . . . |
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| To: tuck who wrote (234) | 2/11/2005 11:06:59 AM | | From: keokalani'nui | | | | This from Yahoo. I listened to the call and brh has it pretty much right. But the comments about the fda and approving for t2 but not t1 were more or less oblique and roundabout in that novo said in at least one conversation with the fda about insulin-affecting drugs--not specifically attributable, but inferred, to pulmonary--it wants to approve a drug not a regimen suggesting that if pulmonary insulin is not safe and effective for all insulin dependent diabetics then this could be a hurdle to approval. I don't know if I feel the same. How is approval for t2 a regimen and approval for t1 and t2 not a regimen?
More interesting were the comments about pharmacoeconomics. Novo says basal insulin will never be delivered to lungs so if you are insulin dependent and getting at least one shot, what government coverage is going to pay 5x for pulmonary pre-prandial where there is no clinical improvement? He said this is especially a concern in EU where novo is getting plenty of heat on its analogues, priced 30% higher than human, which are demonstrably superior. Suggested more potential in US on this issue; 'but ask why our competition has not yet filed.'
Bottom line, this thing looks dead. So to me it appears the only reason for buying it was to lock away all the data from competitors and hibernate the project until perhaps some "ah-ha" moment arrives unlooked for.
Novo comments on ardm insulin
by: brheavy 02/10/05 06:10 pm
Msg: 24814 of 24845
from the webcast today. Novo's comments were
1. that it doesn't appear appropriate for type I diabetics.
2. that the costs don't look good for Europe where they even have a trouble getting a 30% premium for superior insulin analogs.
3. that they are just as far from a product today as when they started!!!
4. that the conversations with the fda indicate they would not approve a filing that did not cover both type I and type II ... (so remember number 1 above) Yikes...
wsw.com
One last comment. Novo's findings suggest T1s are not an appropriate population because, even though it is absorbed as insulin, it works in T1s as an intermediate. Lars continued to say that leaves T2, 'where an intermediate-acting would be appropriate' (presumably for the early stage patient requiring exogenous insulin, but not one with total dependency) but the economics don't look so good.
This is why ardm has lost 20% last 2 days. |
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| To: keokalani'nui who wrote (236) | 2/15/2005 7:28:08 AM | | From: Tadsamillionaire | | | | From the Forbes article...a while back
My view is that the FDA is going to set a very high bar for approving inhaled insulin. The FDA sees delivering drugs through the pulmonary route as a different dosing form. In the FDA's view, the benefit is primarily convenience. In other words, the regulators seem to discount the fact that convenience promotes compliance, which leads to better health outcomes. Therefore, the agency will be extra-cautious in making sure inhaled insulin is safe. For example, the FDA requires two years of safety data, while other forms of injected insulin have been approved on one-year or even six-month data.
Exubera, a dry powder, is inhaled into the lungs before meals. Needles aren't used, and the drug is quickly absorbed into the bloodstream. Nektar scientists took the product through phase I clinical trials and then licensed the technology for further development and commercialization to Pfizer and Aventis. Pfizer and Aventis have a global agreement to co-develop, co-promote and co-manufacture inhaled insulin. Nektar is responsible for manufacturing the fine-insulin powders and supplying the inhalers.
Exubera is awaiting European approval. The companies are planning to file with the FDA for U.S. approval of Exubera by mid-2005. In its deal with Pfizer, Nektar will get 15 percent of all revenue from the product.
forbes.com |
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| From: Tadsamillionaire | 2/15/2005 7:38:19 AM | | | | | | Aradigm Corp (ARDM) Mkt On Open Sell Imbalance: Shrs 54400
09:28 Thursday, February 03, 2005
(END) Dow Jones Newswires
Novo Nordisk Sees 05 Op Pft +5% In DKK
02:12 Friday, January 28, 2005
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