NewNowNext March 31, 2011

A major worry and then a win for blood glucose monitoring and CGM at controversial technology assessment meeting

Tweet

In late March in Olympia, Washington, a committee of 11 doctors (in policy parlance, a “technology assessment committee”) voted on Washington State’s coverage for blood glucose monitoring and for CGM for children 18 and under with diabetes. At risk was not only reimbursement for children in that state but the creation of a dangerous precedent for other states in their reimbursement of diabetic supplies. The thinking went – if Washington State cuts payments, so will the rest of the US. In considering reimbursement coverage, Washington State’s technology assessment committee asked how well blood glucose monitors worked, how safe they were, and how cost-effective they were. Those questions were also asked for CGM. There had been fears that reimbursement for blood glucose monitoring would be declined (this had been the original request), but the committee’s decision sustained strong coverage for the practice – a signature victory for the importance of blood glucose monitoring. Not only did the committee decide to rebuff attempts to reduce coverage (strips are unlimited – whatever these children need they will receive), they opted to cover CGM for kids who have had severe hypoglycemia. CGM coverage for kids didn't exist in Washington prior to this meeting. The coverage will not likely be limited since severe hypoglycemia is very common in children. diaTribe Advisory Board member Dr. Irl Hirsch of the University of Washington told the committee: "Don't mix up evidence-based medicine with ignorance-based medicine." And they didn't. Hurrah!  –KC 

Dexcom receives CE Mark approval for its fourth-generation CGM sensor

Tweet

Dexcom recently received CE Mark approval for its fourth-generation CGM sensor, clearing the new sensor for use in Europe. The company plans to first feature the sensor in an integrated CGM/pump system developed in partnership with Animas, pending approval of the integrated system currently under review in the European Union. As a reminder, Dexcom's fourth-generation sensor is reported to be more accurate than the SEVEN PLUS (including 25% better accuracy in the hypoglycemic range), 50% smaller by volume, have significantly stronger sensor wires,  a faster startup time (one hour instead of two), and allows for reliable readings sooner after insertion. Dexcom plans to submit the sensor to the FDA in the US by late summer, so our best-case scenario estimates are that the solo sensor could be available in the US by late 2011/early 2012. We expect Animas and Dexcom will submit the integrated system in the US sometime soon after filing the sensor itself. The fourth-generation sensor will also be part of the Dexcom/Insulet integrated system, which is expected to be filed with regulatory agencies in the first half of 2012. –ST

Insulet and GlaxoSmithKline to bring the OmniPod to Canada

Tweet

GlaxoSmithKline is partnering with Insulet to make the OmniPod available in Canada for the first time. Under the new partnership, Insulet will continue to manufacture the OmniPod while GlaxoSmithKline will handle all other business aspects involved in getting the product to Canadian customers. The wireless pump is already approved by the regulatory authorities in Canada, and GlaxoSmithKline has begun to sell it. We have sung the praises of the OmniPod previously (see our Test Drive in diaTribe #4), and we are glad to see this technology made available in more countries. Looking to the future, GlaxoSmithKline also plans to make the second-generation OmniPod available in Canada once it has received regulatory approval, which Insulet hopes will be achieved in the next year. The new pod will be a third smaller and 25% lighter. –ST

Immunotherapy for New-Onset Type 1 Diabetes Falters in Clinical Trials

Tweet

In a major disappointment, two treatments for new-onset type 1 diabetes that were previously hailed as breakthroughs have floundered in clinical trials. The two treatments, teplizumab and otelixizumab, are known as anti-CD3 antibodies. These antibodies are designed to block immune cells from destroying insulin-producing beta cells, thereby slowing the progression of type 1 diabetes (see our Learning Curve in diaTribe #15). The Juvenile Diabetes Research Foundation (JDRF) and the National Institutes of Health (NIH) contributed significantly to the early development of these anti-CD3 antibodies. Subsequently, the JDRF partnered with two biotech companies, MacroGenics and Tolerx, which began commercial development of teplizumab and otelixizumab, respectively.

The initial results for both of these anti-CD3 therapies were very promising. In phase 2 trials, individuals treated with either therapy had significantly less destruction of beta cells and more  insulin secretion many months after type 1 diabetes was diagnosed. However, larger subsequent clinical trials have failed to replicate these early results. The first piece of disappointing news came last October, when MacroGenics and its partner, Eli Lilly, announced that they had suspended developing teplizumab after it failed to show efficacy in a year-long phase 3 trial. Earlier this month, Tolerx and its partner, GlaxoSmithKline (GSK), reported similarly disappointing results from a large trial of otelixizumab called DEFEND-1. In light of these results, the companies halted DEFEND-2, their second large trial of otelixizumab. However, Tolerx and GSK have indicated that they will continue to study otelixizumab to see if other doses can be more effective. Although anti-CD3 therapy has suffered an enormous setback, the road ahead for this and other immune-modulating therapies in new-onset type 1 diabetes has not been closed off. –MY

Bydureon found to be not as effective as Victoza in DURATION-6 trial

Tweet

In early March, Amylin/Eli Lilly/Alkermes released results from the much-anticipated DURATION-6 trial, in which their once weekly GLP-1 agonist Bydureon was compared with Victoza, Novo Nordisk’s once daily GLP-1 agonist. As a reminder, GLP-1 agonists help to lower blood glucose levels, are not associated with hypoglycemia, promote weight loss, and are in general well tolerated (see our Learning Curve in diaTribe #8). Bydureon is not yet approved by the FDA, but is scheduled to be submitted for review later this year, with a potential approval in the first half of 2012 (see our Learning Curve in diaTribe #26 for more on Bydureon’s regulatory status). In the DURATION-6 study, Bydureon did not lower blood glucose (measured using A1c) as much as Victoza. After 26 weeks of treatment, participants receiving Bydureon experienced an average 1.3% A1c reduction, while participants treated with Victoza had an average 1.5% reduction in A1c. From a practical perspective, a 0.2% difference in A1c is quite small. In DURATION-6, Bydureon was associated with lower rates of side effects than Victoza: of those on Bydureon, 9% reported nausea, 4% vomiting, and 6% diarrhea, compared to 20% nausea, 11% vomiting, and 13% diarrhea in those on Victoza. Bydureon’s once weekly injection (compared to once daily with Victoza) and lower nausea rates will likely make it an attractive option once approved, despite being found in this study to be slightly less effective than Victoza at controlling blood sugar levels. We believe that currently about one million people with type 2 diabetes globally take GLP-1 agonists and that that number will climb substantially in 2011 and beyond.  –VW

Promising Results Reported for Once Monthly GLP-1 Agonist; Bydureon Inches Closer to Possible Approval

Tweet

For type 2 patients, the use of GLP-1 agonists (such as Victoza and Byetta) can often lead to significant improvements in blood glucose control and weight loss with little risk for hypoglycemia. Animal studies have even suggested that these therapies possess a protective effect on beta cells (potentially slowing or halting beta cell death) and on the cardiovascular system (possibly reducing the risk for heart attacks, stroke, heart disease, etc.). Despite these benefits, the need to administer GLP-1 agonists by injection (twice daily injections with Byetta and once daily injections with Victoza) is sometimes a notable barrier to beginning the therapy and adhering to it. Fortunately, several companies have begun developing longer-acting GLP-1 agonists in an effort to reduce the number of injections.

Two such companies are Amylin and Eli Lilly, the makers of Byetta, which are again teaming up to develop once-weekly and once-monthly GLP-1 formulations. Bydureon, the once-weekly formulation, has already successfully finished phase 3 human studies, demonstrating an ability to provide greater blood glucose control (determined by A1c) and similar weight loss as Byetta but with reduced rates for nausea and vomiting (common side effects associated with GLP-1 agonists). The companies recently announced that a small trial (called a thorough QT study) that will examine Bydureon’s effect on the heart was initiated in February and will be completed by the end of this year. If all goes according to plan, Bydureon may be approved in the US by mid-2012 (for more information on Bydureon, please see the Learning Curve in diaTribe issue # 26).

Amylin and Eli Lilly have also recently reported positive results from a small phase 2 study that compared their once-monthly GLP-1 formulation (referred to as exenatide once-monthly) to Bydureon. Like Bydureon, exenatide once-monthly is composed of exenatide, the active ingredient found in Byetta, and microscopic spheres that slowly release the drug into the bloodstream. Unlike Bydureon, however, exenatide once-monthly does not require reconstitution (mixing the drug into solution) before administration, a feature that should improve ease of use. In the 20-week study, participants receiving exenatide once-monthly achieved similar improvements in blood glucose control (average A1c reductions between 1.3% and 1.5%) as those receiving Bydureon (average A1c reduction of 1.5%). Both drugs also appeared to be safe and tolerable with no minor or major hypoglycemic events reported and with headache and nausea (for exenatide once-monthly) and headache and diarrhea (Bydureon) listed as the most common adverse events associated the respective therapies. Although promising, these results will need to be confirmed in larger and longer phase 3 trials, meaning that exenatide once-monthly will not likely become available for at least three years.  Yet the prospect of a once-monthly drug for type 2 diabetes is certainly exciting, and we look forward to keeping you updated as we hear more news in months and years to come. --BK