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Homepage: www.amylin.com Es handelt sich um folgende zwei Medikamente mit einem Marktpotenzial von jeweils 1 Milliarde $ (geschätzt): SYMLIN® (pramlintide acetate) SYMLIN® is a unique injectable product candidate intended for the treatment of patients with type 1 diabetes and insulin-using patients with type 2 diabetes. Other than insulin and insulin analogues, SYMLIN® is the first potential treatment addressing glucose control for patients with type 1 diabetes that has completed Phase 3 clinical trials since the discovery of insulin over 80 years ago. In clinical studies, SYMLIN® has demonstrated improvements in blood glucose control in people treated with insulin alone, or insulin plus one or more oral medications, without causing a weight increase. Scientific Overview SYMLIN® is a synthetic version of the human hormone, amylin. It is the first member of a new class of therapeutic medications known as amylinomimetic agents, or amylin receptor agonists. Amylinomimetic agents mimic the actions of the hormone amylin and have demonstrated activity in blood glucose regulation. Amylin is made in and secreted from the same cells in the pancreas that make and secrete insulin. These pancreatic cells are called beta cells. In normal physiology, amylin complements the actions of insulin, and these two hormones work together with another pancreatic hormone, glucagon, to maintain normal glucose concentrations. Along with insulin, amylin concentrations normally increase and glucagon levels decrease after meals. In people with type 1 diabetes, insulin and amylin concentrations are extremely low or undetectable and do not increase after meals, and conversely, glucagon levels tend to rise after meals. In people with type 2 diabetes whose disease has progressed to the point where they need insulin therapy, the normal post-meal increase in insulin and amylin concentrations also fails to occur, and glucagon levels also are inappropriately elevated in the post-meal period. These hormonal abnormalities contribute significantly to the disturbance of glucose metabolism in the context of a meal. Replacement of insulin alone, the current therapy, cannot replace amylin’s actions nor can insulin normalize post-meal glucagon concentrations. Clinical Trials More than 5,000 patients have been treated with SYMLIN. Amylin has completed six Phase 3 clinical trials with various doses of SYMLIN® as well as numerous Phase 2 and Phase 1 trials. Additionally, the company has completed long-term open-label safety trials and open-label extensions of the Phase 3 clinical trials to assess long-term effects of SYMLIN®. Phase 3 trials have shown a statistically significant reduction in A1C levels for both type 1 and insulin-using type 2 patients. Data from short-term clinical trials involving both type 1 and insulin-using type 2 diabetes patients showed that SYMLIN®, as an adjunct to insulin, can: prevent the abnormal rise in glucagon after meals; slow the rate of gastric emptying; and reduce the range of after-meal variations in blood glucose levels. Across all of long-term Phase 3 SYMLIN® clinical trials, patients with type 1 and type 2 diabetes receiving the recommended dosage of SYMLIN®, in addition to their existing diabetes therapy, achieved an average additional reduction in A1C of 0.3% and 0.4%, respectively, at the end of 26 weeks (compared to patients using insulin with placebo). In these studies, patients with type 2 diabetes who were treated with SYMLIN® lost an average of 3.3 pounds during the trial period, while patients with type 2 diabetes in the control group gained an average of 0.7 pounds. Trial participants with type 1 diabetes who received the recommended dose of SYMLIN lost an average of 2.4 pounds at the end of 26 weeks, while those patients receiving insulin and placebo gained an average of 1.5 pounds. In the two most recent SYMLIN® Phase 3 clinical trials, each of which lasted 52 weeks, patients with type 1 and type 2 diabetes receiving the recommended dosage of SYMLIN® in addition to their existing diabetes therapy achieved an average additional reduction in A1C levels of 0.4% and 0.6% respectively (compared to patients using insulin with placebo). In these trials, patients with type 2 diabetes treated with SYMLIN lost an average of 3.1 pounds during the trial period, while patients with type 2 diabetes in the control group gained an average of 1.5 pounds. Trial participants with type 1 diabetes who were overweight upon trial entry and who received the recommended dose of SYMLIN lost an average of 3.5 pounds during the trial period, while patients receiving insulin and placebo gained an average of 3.5 pounds. In long-term SYMLIN clinical trials of 26 or 52 weeks, the addition of SYMLIN® did not adversely affect patients’ lipids or blood pressure. The most commonly occurring side effects in the SYMLIN® trials have been nausea, anorexia and vomiting, which were generally mild to moderate in intensity, were dose related, occurred early in treatment and generally dissipated over time. In April 2002, after consultation with the FDA, Amylin initiated a seven-month dose titration study of SYMLIN focused on safety involving approximately 300 subjects with type 1 diabetes. The data from this study indicated that initiation of SYMLIN® therapy using a dose-titration protocol reduced the impact of nausea and that SYMLIN® was associated with a positive effect on post-meal glucose. The data also showed a reduction in A1C at 16 weeks consistent with the non-inferiority objective for the study. As shown in previous pivotal studies, the SYMLIN® treated subjects used less insulin and had a reduction in weight, and the control group used more insulin and gained weight. SYMLIN dose titration also reduced the incidence of severe hypoglycemia during the initiation phase of this study compared to earlier pivotal trials. The rate of severe hypoglycemia observed is consistent with that seen in the landmark Diabetes Control and Complication Trials. Approximately 75% of the SYMLIN® treated subjects progressed to the highest trial dose of 60 micrograms, in accordance with the protocol, and experienced a similar rate of severe hypoglycemia to the control group during the titration period. Doses of SYMLIN higher than 30 micrograms were not well tolerated by approximately 25% of subjects. This group experienced higher rates of nausea with initiation of therapy and subsequently experienced higher rates of hypoglycemia. Most of the 30 microgram dose subjects chose to continue in the study and experienced reductions in both post-meal glucose and A1C. Conclusions cannot be drawn with respect to severe hypoglycemia until data is available from the full seven months of treatment. Regulatory Status In December 2000, Amylin submitted a New Drug Application, or NDA, for SYMLIN® to the FDA. In October 2001, the company received a letter from the FDA stating that SYMLIN® was approvable for marketing in the United States, as an adjunctive therapy with insulin, for the treatment of type 1 and insulin-using type 2 diabetes patients, subject to satisfactory results from additional clinical trials. In April 2002, Amylin commenced the seven-month dose titration study, and in March 2003 all patients completed the study. The company also completed four smaller trials to clarify suggested prescribing information. Based on the approvable letter from the FDA, Amylin believes that efficacy for SYMLIN® has been established. As a result, the dose titration study employed a “non-inferiority” design to permit evaluation of the results without having to demonstrate statistically significant differences in efficacy between the SYMLIN® and placebo treatment groups. While focusing principally on safety, however, Amylin expects the FDA will want the safety of SYMLIN® to be established without giving up improvements in glucose control or other important parameters of diabetes management. Amylin submitted an NDA amendment for SYMLIN in June of 2003 and received a second approvable letter in December 2003. Discussions are underway with the FDA to identify specific requirements for approval. Amylin submitted a Marketing Authorization Application, or MAA, for SYMLIN® to the European regulatory authorities in May 2001. In October 2002, following consultation with the European Committee for Proprietary Medicinal Products, Amylin determined that additional information would be required for approval of SYMLIN in Europe. The European centralized regulatory procedure provides no mechanism for adding new information to an application in progress; therefore, Amylin withdrew the MAA for SYMLIN®. The company is engaging in further discussions with European regulatory authorities and other regulatory experts to clarify regulatory alternatives and requirements for SYMLIN®. In August 2001, Amylin submitted an application for SYMLIN® to regulatory authorities in Switzerland (Swissmedic). Amylin submitted interim summary data from the SYMLIN® dose titration trial and study reports from four smaller studies at the request of the Swiss authorities in March 2003. The interim summary was performed with concurrence from the FDA, and the FDA received a copy of the Swiss submission. In January 2004, Amylin withdrew the regulatory application after receiving correspondence from the Swissmedic indicating that SYMLIN® could not be approved for marketing in Switzerland based on data received to date. The Swiss regulatory procedure does not allow for another supplemental submission of data at this stage. The revision in Amylin’s Swiss regulatory strategy for SYMLIN® does not affect regulatory strategies being pursued in the U.S. Target Market The primary patient population focus for SYMLIN® is people with diabetes who use insulin. This target population currently has limited therapeutic options. Patients with type 1 diabetes have complete beta cell deficiency and must use insulin to sustain life or undergo islet transplant therapy, which, in some cases, can temporarily render them insulin-independent. Patients with type 2 diabetes who have progressed to insulin therapy have typically exhausted other therapeutic options for improved blood glucose control due to advanced beta cell dysfunction. Amylin estimates that this group is made up of approximately 4.5 million people in the United States based on published and proprietary estimates. Within this population group, the company estimates that approximately one million people have type 1 diabetes, and the remaining 3.5 million have type 2 diabetes. SYMLIN® is an injectable product and Amylin plans to market it in syringe/vial form and a pen/cartridge system similar to those currently marketed with newer insulin preparations. |
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| aus der Diskussion: | Amylin - Zwei mögliche Blockbuster-Zulassungen im Frühjahr!!! |
| Autor (Datum des Eintrages): | blb (16.01.05 10:14:03) |
| Beitrag: | 4 von 37 (ID:15541110) |
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