| To: tuck who wrote (209) | 6/10/2004 1:24:55 PM | | From: tuck | | | | Thanks to deeno for this ML report which mentions for the first time in the analytical domain (that I have seen) the ARDM/Novo experience as a potential problem for Exubera.
Message 20210503
Cheers, Tuck |
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| To: rkrw who wrote (196) | 8/10/2004 3:28:44 PM | | From: tuck | | | | >>CAMBRIDGE, Mass.--(BUSINESS WIRE)--Aug. 10, 2004--Alkermes, Inc. (Nasdaq: ALKS - News) 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.
About Diabetes
Diabetes is a group of diseases characterized by high levels of blood glucose resulting from defects in insulin production, insulin action, or both. According to the American Diabetes Association ("ADA"), diabetes can be associated with serious complications and premature death, but people with diabetes can take steps to control the disease and lower the risk of complications (Source ADA). Additionally, the World Health Organization ("WHO") lists diabetes as one of the leading causes of mortality worldwide. Approximately 193 million people around the world have diabetes, and this number is expected to double to 330 million by the year 2025 (Source International Diabetes Federation). <<
There is no thread for Alkermes, according to the lame SI search engine. NKTR recently got creamed by EMEA "not licensable" letter a few days ago. Not sure what the specific concerns were, but one wonders if the antibody issue is haunting them, too. Will Lilly and Alkermes really escape? NKTR is up 10%, ALKS 20% . . . and ARDM is still in its hospital bed.
Cheers, Tuck |
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| To: tuck who wrote (211) | 8/24/2004 10:52:05 AM | | From: tuck | | | | [Intrasubject variability of inhaled insulin in type 1 diabetes: a comparison with subcutaneous insulin.]
>>Diabetes Technol Ther. 2004 Aug;6(4):466-72.
Intrasubject variability of inhaled insulin in type 1 diabetes: a comparison with subcutaneous insulin.
Kapitza C, Hompesch M, Scharling B, Heise T.
Profil Institute for Metabolic Research, Neuss, Germany.
We compared intrasubject variability of insulin and glucose profiles after a standardized meal between insulin inhaled via the AERx((R)) insulin Diabetes Management System (AERx iDMS, Aradigm Corp., Hayward, CA) and given as a subcutaneous injection. In this single-center, parallel, randomized, open-labeled trial, 17 male, non-smoking patients with type 1 diabetes (mean age, 27.7 years; body mass index, 23.4 kg/m(2)) received a fixed, individualized dose of human insulin, on four treatment days followed by an individualized breakfast, administered either by inhalation via AERx iDMS (n = 9) or by subcutaneous injection. Serum insulin and serum glucose levels were determined at regular intervals for 6 h postdose. Intrasubject variability was expressed as coefficient of variation. No statistically significant differences in intrasubject variability were observed between the treatments for the areas under the insulin curves for 0-6 h [27% vs. 19% (inhaled insulin vs. subcutaneous)] and areas under the glucose curves 0-6 h (30% vs. 23%). Intrasubject variability values for insulin half-life, terminal elimination rate constant, and mean residence time were significantly less in the inhaled insulin group compared with the subcutaneous insulin group (P = 0.01-0.02). Only one potentially trial product-related adverse event (an audible wheeze) was reported, and no clinically relevant changes in pulmonary function were detected. The intrasubject variability was comparable between patients receiving inhaled insulin and subcutaneous insulin, thereby confirming the reproducibility of administering insulin via AERx iDMS. Inhaled insulin was well tolerated and is a feasible alternative to subcutaneous insulin in patients with type 1 diabetes.<<
Nothing major here . . .
Cheers, Tuck |
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| To: tuck who wrote (212) | 8/26/2004 11:54:58 AM | | From: tuck | | | | Now KOSP is playing in the inhaled insulin space, too. Here's the relevant snip from a PR today:
>>The results of the phase IIa trial show that Kos' internally developed inhaled insulin formulation is comparable to the market leading injectable insulin in controlling blood glucose levels, while also reducing blood lipids such as LDL cholesterol and triglycerides. (Please note table of summary results below.) Kos' inhaled insulin formulation also demonstrated bioavailability of up to 23% in a previous phase I human study. The successful completion of these phase I and IIa studies support the safety and efficacy of Kos' patient-friendly, excipient-free formulation.
In the head-to-head comparative study of 24 type 2 diabetic patients, insulin-naive patients were randomized to receive either Kos' inhaled insulin formulation at meals or a single evening injection of insulin glargine, a basal insulin analog marketed by Aventis Pharmaceuticals Inc. under the brand name Lantus® (and currently the most prescribed insulin in the U.S.). Following a one-month treatment period, Kos' inhaled insulin formulation demonstrated a mean reduction in blood glucose of 28%, compared with a mean reduction of 23% with insulin glargine. Kos' formulation also showed a trend toward greater improvement with respect to hemoglobin (Hb) A1c, showing a mean absolute reduction of 1.23 mg/dL, compared with a mean absolute reduction of 1.05 mg/dL with insulin glargine. The safety profiles of both treatments were comparable, with four mild to moderate hypoglycemic episodes occurring in both groups. Additionally, Kos' inhaled insulin formulation produced a 10% reduction of LDL cholesterol at day 28, compared with an increase of 1.4% with insulin glargine. Similarly, triglycerides were reduced by 36% with Kos' inhaled formulation, compared with a 12% reduction with the injectable insulin. Such results are quite important in so far as many type 2 diabetics not only require good control of blood sugar, but also require modulation of abnormal lipids, which occur in more than 60% of all diabetics.
SUMMARY DATA FROM PHASE IIa STUDY IN TYPE 2 DIABETES
Day 7 Day 28
------------------------- --------------------------
Kos Injectable Kos Injectable
Inhaled Insulin Inhaled Insulin
Insulin glargine Insulin glargine
------- -------- ------- --------
(n=12) (n=12) (n=12) (n=12)
Mean Change in
Glucose (%) -26.8 -24.8 -27.8 -23.1
Absolute Change
in Hb A1c
(mg/dL) -0.23 -0.18 -1.23 -1.05
LDL Cholesterol
(%) -5.2 1.9 -9.9 1.4
Triglycerides
(%) -40.7 -28.6 -35.8(1) -11.5
(1) Significant at p less than or equal to 0.05 vs. injectable
insulin glargine (Lantus). Given the small sample size of the study,
statistical significance was not observed with the exception of
triglycerides at day 28, however, results did show trends toward
improvement in post-prandial measures of blood glucose and blood
lipids.
"Injections have long been a hurdle in the treatment of certain patients with diabetes," said Jay Skyler, MD, Director of Endocrinology, Diabetes, and Metabolism, University of Miami. "A user-friendly inhaled insulin product will open the door for patients who have been hesitant to start therapy or comply with their current treatment."
Kos' excipient-free formulation coupled with Kos' patented compact, hand-held Breath Actuated Inhaler ("BAI") device offers a precision lung delivery platform for insulin therapy. The Kos formulation, which does not require refrigeration, contains no carriers or preservatives and incorporates a crystalline, recombinant human insulin (rh-insulin) delivered by a standard, well-tested non-CFC, environmentally-friendly propellant. In clinical testing, patients and physicians were impressed with the ease of use of the patented BAI delivery system in administering insulin therapy, potentially improving patient compliance. Both the excipient-free formulation and the BAI device were entirely developed internally by Kos. The Company is seeking a corporate partner to complete the clinical development of its innovative inhaled insulin product.
"We are extremely excited about the achievement of these important R&D milestones in both the solid dose and inhalation areas," said Adrian Adams, President and CEO, Kos Pharmaceuticals, Inc. "Kos' inhaled insulin formulation is expected to confer highly potent and patient-friendly insulin therapy that is well tolerated, possibly allaying side effects that have been observed with other preparations of inhaled insulin therapy. This formulation was designed to eliminate specific chemical additives, some of which have been associated with certain pulmonary side effects and have been cited as an issue with earlier generations of inhaled insulin. Further, this excipient-free, user-friendly technology is a product of our continued and measured investments in our inhalation platform, consisting of proprietary formulation and device technologies."<<
Cheers, Tuck |
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| To: tuck who wrote (213) | 8/26/2004 12:45:35 PM | | From: rkrw | | | | | KOSP program has been around a long time. Any idea why kosp is able to get such dramatic drops in ldl and triglycerides with inhalation? I wonder how it compares with exubera and aerx? |
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| To: rkrw who wrote (214) | 8/26/2004 1:12:42 PM | | From: tuck | | | | No, though that struck me, too. I don't know why KOSP is targeting those parameters. If they've been measured for competing systems, I haven't been able to find any data or even mention of it. What struck me as more crucial was the "excipient-free" formulation. Wondering if AERx and Exubera use excipients that might cause those pulmonary problems. Don't think that relates directly to AERx' night time glucose level issues, though.
Cheers, Tuck |
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| To: tuck who wrote (215) | 8/26/2004 1:34:43 PM | | From: rkrw | | | | | Exubera does use excipients. I think that was one of the advantages aerx over exubera. Been so long since I paid any attention... |
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| To: rkrw who wrote (216) | 9/6/2004 5:29:50 PM | | From: tuck | | | | >>MUNICH, Germany, Sept. 6 /PRNewswire-FirstCall/ -- MannKind Corporation (Nasdaq: MNKD - News) presented scientific information today at the Annual Meeting of the European Association for the Study of Diabetes being held in Munich, Germany that described desirable features of insulin delivery and glucose control with its Technosphere®/Insulin system that are not available from currently marketed insulin or oral diabetes drug therapies. Currently in late stage Phase II clinical trials in the United States and Europe, the MannKind product is being developed to treat both type 1 and type 2 diabetes mellitus.
Dr. Wendell Cheatham, Corporate Vice President for Medical & Regulatory Affairs of MannKind Corporation and an Endocrinologist/Diabetologist, described the ability of Technosphere®/Insulin to produce a rapid increase in blood insulin level that approximates the normal early release of insulin that is observed in healthy individuals in response to a meal. Dr Cheatham noted that this early insulin signaling spike is lost in patients who suffer from both type 1 and type 2 diabetes and commented, "There is currently no marketed form of therapy for diabetes that has been able to replace or restore the signaling function of the healthy pancreas. This rapid signal is not directly involved in glucose disposal, but is needed to stop release of glucose from the liver when nutrients are being ingested in a meal. Glucose is released by the liver to fuel the body between meals, but this additive glucose is undesirable during and shortly after absorption of nutrients from a meal. Turning off the release of glucose from the liver during this meal-time period is extremely important in controlling blood sugar levels."
Dr. Cheatham presented data on the speed of absorption and pharmacological characteristics of MannKind's inhaled insulin that were similar to results seen when regular insulin was injected directly into the blood stream. In addition, the Technosphere®/Insulin system was shown to have an effect that spans the period of meal digestion and absorption. Dr. Cheatham also described a model of human glucose dynamics that MannKind developed in order to better understand why the effect of its inhaled insulin is different from that produced by insulin given via subcutaneous injection and why it is more similar to the effect of insulin given by intravenous injection. MannKind plans to present information from completed Phase II studies of its inhaled Technosphere®/Insulin to the US FDA before the end of 2004.
About MannKind Corporation
MannKind focuses on the discovery, development and commercialization of therapeutic products for diseases including diabetes, cancer, inflammatory and autoimmune diseases. The Company's lead product, the Technosphere® Insulin System, which is currently in late Phase II clinical trials for the treatment of diabetes, consists of a proprietary dry powder Technosphere® formulation of insulin that is inhaled into the deep lung using MannKind's MedTone(TM) inhaler. Early indications show MannKind's proprietary Technosphere® Insulin System's performance characteristics, convenience and ease of use have the potential to change the way diabetes is treated. For more information on MannKind Corporation and its technology, visit www.mannkindcorp.com. <<
snip
Cheers, Tuck |
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| To: rkrw who wrote (218) | 9/17/2004 11:01:36 AM | | From: tuck | | | | [Inhaled morphine delivered using the AERx system in patients with moderate-to-severe asthma]
>>Int J Clin Pharmacol Ther. 2004 Aug;42(8):456-62.
Safety and pharmacokinetics of inhaled morphine delivered using the AERx system in patients with moderate-to-severe asthma.
Otulana B, Okikawa J, Linn L, Morishige R, Thipphawong J.
Aradigm Corporation, Hayward, CA 94545, USA. totulana@aradigm.com
OBJECTIVE: The safety and pharmacokinetics of inhaled morphine in asthmatic subjects were investigated using the AERx System, a novel aerosol system. METHODS: Twenty subjects with asthma received inhaled placebo and inhaled morphine sulfate, 2.2 mg, 4.4 mg and 8.8 mg, on separate days in a single-blind crossover study. Six of the subjects received an additional open-label dose of 17.6 mg on a separate day. Plasma morphine concentrations and safety evaluations including pulmonary function testing were performed. RESULTS: Mean tmax values were similar following all dose groups at approximately 1-2 minutes. Mean AUC(0-->1) values showed dose proportionality for the first 3 dose groups (6.3, 12.3 and 24.3 ng x h x ml(-1)), the mean AUC(0-->1) for the 17.6 mg dose group was 1.6x that of the 8.8 mg dose group. No statistically significant differences in forced expiratory volume in 1 sec (FEV1) were found for the 2.2 mg, 4.4 mg, or 8.8 mg dose groups; at 17.6 mg, a statistically significant but not clinically meaningful reduction in mean FEV1 (-8.18%) from baseline occurred at 10 minutes compared to placebo, spontaneously returning to baseline by 60 min. Four subjects experienced significant but reversible decreases in FEV1 of > or = 20% compared to baseline and across all dose levels including after placebo, but with no associated increase in dyspnea, wheezing or other adverse events. CONCLUSIONS: Inhaled morphine using the AERx System was absorbed rapidly and demonstrated dose-dependent plasma concentrations. It was well-tolerated and did not cause clinically significant bronchoconstriction in most subjects with moderate-to-severe asthma.<<
Cheers, Tuck |
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