It seems that the business websites are often the first to report the financial impact when pharmaceutical trials succeed or fail. Indeed, Ann Bartlett, once again has alerted me to the latest failure in the attempt to cure type 1 diabetes. The Diamyd trial fails to meet its primary efficacy endpoint. Unfortunately, the Diamyd trial has now joined the Protégé and Defend Monoclonal antibody trials in documenting the inability to improve c-peptide concentrations.
To review, in a recent blog, I posted diabetes research updates (failure of DEFEND II) and the latest information about the Diamyd trial (GAD-65 vaccine). As I discussed previously, The EU Diamyd Phase III clinical study was a multicenter (Finland, France, Germany, Italy, the Netherlands, Slovenia, Spain, Sweden, and the United Kingdom), double-blind, randomized, placebo-controlled trial, enrolling 320 patients (10 to 20 years old within 3 months of diagnosis of type 1 diabetes). The goal of the global phase III trial was to determine if Diamyd could stop or slow pancreatic Beta cell destruction; thus preserving insulin production and the ability to control blood sugars. Phase II trials were successful: demonstrating the ability to slow the loss of beta cell function as compared to placebo.
In the phase III trial, 33 percent of patients received four injections with Diamyd, 33 percent received two injections with Diamyd, followed by two injections with placebo, and 33 percent received four injections with placebo. The injections were given on day one, one month, three months, and nine months. The results were then compiled and analysis of the data from the 60 European clinics was conducted and the study became "unblinded."
As I alluded to above, "Diamyd Medical AB reported that the results from its European Phase III study with antigen-based therapy Diamyd did not meet the primary efficacy endpoint of preserving beta cell function at 15 months as measured by meal stimulated C-peptide, in newly diagnosed type 1 diabetes patients."
More specifically, "the Phase III study did not show a statistically significant preservation of beta cell function after 15 months of follow-up as compared to placebo, although a small positive effect was demonstrated." The Diamyd follow-up will continue for an additional 15 months to further delineate the safety and efficacy of the GAD-65 vaccine.
The Diamyd global phase III program in the United States (DiaPrevent) is fully enrolled as of December 2010. According to Diamyd Medical, the results of the study are expected to be completed during the summer of 2012.
The alpha-1-antitrypsin trial in new onset type 1 diabetes is still ongoing. To review: the goal of the AAT study is to determine if alpha-1-antitrypsin could help to stop or delay destruction of beta cells in people diagnosed with type 1 diabetes within 90 days. People with new onset type1 ages 6 to 45 are currently being enrolled and the study drug is provided at monthly visits (vs. placebo) for 12 months. At the end of 2 years, study participants who continue to produce insulin will be asked to come for visits every 6 months for an additional 2 years.
I had the pleasure of meeting with Dr. Eli Lewis, the primary investigator (PI) at Children's National Medical Center. The initial data was very promising, especially in view of the fact that the safety profile of Alpha-1 antitrypsin has already been established in the treatment of Alpha Antitrypsin Deficiency (gastrointestinal disease).
As a clinician caring for children and adolescents with diabetes, I am often asked (usually at the time of diagnosis) whether or not to enroll in a medical trial looking to prolong beta cell life. If the child or adolescent is able to understand the concepts behind the trial, it is important to try to explain in as much detail as possible what the trial entails. Even with children and adolescents, informed consent is the ideal and every effort should be made to obtain it. In addition, it is important to emphasize that even if the trial demonstrates positive results or meets the primary efficacy endpoint, it may not mean that the child or adolescent can continue with the trial drug. Essentially, enrolling in a clinical trial may benefit trial participants in the short-term and those people in the future that will be diagnosed with type 1 diabetes. Thus, in my opinion, enrolling in a clinical trial should be considered an act of altruism. Keep in mind that although these particular research trials have failed to reach primary efficacy endpoints, many improvements in the clinical care of diabetes are ongoing in an effort to continually improve quality of life.
I will continue to keep you posted.
Published On: May 18, 2011