NewNowNext April 29, 2011
Bydureon Recommended for Approval in Europe
In mid-April, the European Medicine Agency's Committee for Medicinal Products for Human Use (a committee called the "CHMP") recommended that Amylin/Lilly/Alkermes' once-weekly GLP-1 agonist Bydureon be approved in Europe as an add-on therapy; it would be for adults with type 2 diabetes who haven't achieved adequate glycemic control on maximally tolerated doses of many common oral drugs. Yippee! We've been waiting for the approval of Bydureon for a long time and we are excited that people with type 2 diabetes will likely soon have this as an option in Europe. As background, in Europe, medicines such as Bydureon undergo CHMP review before the European Medicines Agency (the EMA for short – the equivalent of the FDA in Europe) decides whether or not to approve them. The EMA is expected to make its decision on Bydureon in late June; given the CHMP's positive recommendation, it seems likely that Bydureon will be approved in Europe this summer. We sure hope so since it would be the first once-weekly drug approved for people with type 2 diabetes. Meanwhile, in the US, the earliest Bydureon could be approved is mid-2012, given its recent regulatory setbacks (see our Learning Curve in diaTribe #26 for more). Regardless, the prospect of this once-weekly GLP-1 agonist reaching the market in the not-too-distant future is exciting, as it might be easier for people with type 2 diabetes to take it regularly and thus improve their glycemic control.–VW/KC
Medtronic Introduces Mac-Compatible Software in the US and Its New Enlite Sensor in the EU
In Europe, Medtronic's new Enlite sensor received CE mark approval for six-day wear and will be launched in over 35 countries outside of the US this spring.
April has been quite a busy month for Medtronic with the launch of new CareLink software that is finally Mac-compatible and the introduction of the greatly anticipated new Enlite continuous glucose monitoring sensor overseas.
The FDA approved the new CareLink Personal 5.4 software, which will allow US Mac users to access web-based tools that allow them to download meter or CGM data and analyze glucose data with a variety of reports, charts, and graphs. Over 35 blood glucose meters, some of which are not Mac-compatible through their own manufacturer's software, will be supported on the new free CareLink platform. The software is compatible with the latest operating software for both Mac (Mac OS 10.6 and 10.5 Intel-based computers) and Windows (Windows 7, Vista, and XP). diaTribe's own Adam Brown is now testing Medtronic's CareLink Pro 3.0 for the next edition of Test Drive.
In Europe, Medtronic's new Enlite sensor received CE mark approval for six-day wear and will be launched in over 35 countries outside of the US this spring. This sensor has been highly anticipated as it is designed to be both more comfortable and accurate than previous generations. The new sensor is 69% smaller by volume and half the length of the previous Medtronic sensor, now a 27-gauge needle at its thinnest point. The insertion process is also easier and less intimidating, with a vertical 90-degree insertion technique that keeps the needle hidden the entire time. In addition, the device is now more accurate due to several design improvements, including less temperature-driven volatility and fewer adverse interactions with drugs. We see these features as welcome improvements by all CGM users, but particularly for children (and their parents!). Unfortunately for those in the US, it seems that the FDA's conservative stance may set back approval by at least another year. See this issue's Test Drive for an update on the Enlite from Greek diabetes patient advocate and diaTribe reader Nikos Filippou. –JS
Onglyza Now Approved for People with Type 2 Diabetes Who Have Kidney Problems
Ongylza was recently approved by the FDA for use by people with type 2 diabetes who have a failed or impaired kidney.
People with diabetes are at significantly increased risk for kidney impairment or kidney failure. Kidney disease can complicate the treatment of type 2 diabetes because some medications should not be used for people with kidney problems. For example, metformin, the most commonly used first-line therapy for type 2 patients, should be avoided by those who have kidney disease because it can occasionally accumulate in the body, causing a condition known as lactic acidosis. For a diabetes medication to be used in people with kidney impairment, a drug manufacturer must first show that it is safe in this population, and then seek approval from the FDA for this indication. Onglyza, the second drug belonging to a new class of medication called DPP-4 inhibitors (the first was Januvia), recently obtained approval from the FDA for use in those who have a failed or impaired kidney. Supporting this expanded label, the drug manufacturer had conducted a 12-week study of Onglyza (2.5 mg dose) showing that it could safely lower blood glucose (0.9% A1c reduction on average from a baseline of 8.1%) in people with kidney impairment or failure. The rate of serious side effects and discontinuations was similar between Onglyza and a placebo (inactive pill) in this trial. Also, a recent clinical trial documented the potential benefits of initiating Onglyza compared to a sulfonylurea called glipizide in people who are already treated with metformin. In this study, people treated with Onglyza had significantly less weight gain and a remarkable 12-fold lower rate of hypoglycemia than people treated with glipizide. Reduced hypoglycemia and less weight gain are well-established benefits of DPP-4 inhibitors, including Onglyza. --MY
The International Diabetes Federation Recommends the Consideration of Bariatric Surgery for Less Obese Individuals with Type 2 Diabetes
In late March, the International Diabetes Federation (IDF) released a "position statement" recommending the consideration of bariatric surgery to treat type 2 diabetes for less obese individuals. Specifically, the IDF suggested that people with a BMI (a combined measure of height and weight) between 30-35 kg/m2 with uncontrolled diabetes (A1c >7.5%) be "eligible for surgery" and those with a BMI between 35-40 kg/m2 be "prioritized for surgery." For context, an individual with a height of 5'7" and a weight of roughly 190 pounds would have a BMI of 30 kg/m2 (you can calculate your BMI using a BMI calculator here). The IDF's position statement marks a departure from the widely accepted guidelines (established in 1991), which recommended that bariatric surgery be considered primarily as a last resort for people with a BMI of at least 40 kg/m2 (e.g., 5'7", 250 pounds), or 35-40 kg/m2 if excess weight is accompanied by other health-related conditions such as diabetes. The IDF's position statement highlights the potential use of bariatric surgery to treat less obese indivduals with type 2 diabetes; however, it's important to note that the IDF statement is one of many consensus statements on bariatric surgery, most of which still follow the 1991 guidelines.
For readers not familiar with surgery for weight loss, "bariatric surgery" is a term that refers to a group of surgical procedures intended to help people lose weight; the two primary procedures performed in the US are the "gastric band" and the "gastric bypass" (see our NewNowNext in diaTribe #18). These procedures also have profound effects on improving diabetes (more so with gastric bypass than with gastric banding). In one study, about one in three people with diabetes who underwent bariatric surgery were in remission (their glucose was under control and they did not require any diabetes medications, including insulin) 10 years post-operation. While the potential benefits of bariatric surgery are high, so are its risks. Complications associated with the procedures include: leaks from the gastrointestinal tract, wound infections, lung complications, and hemorrhage (bleeding from ruptured blood vessels), in 1-3% of people who undergo the procedures. Unfortunately, long-term surgical complications and the need for surgical revisions are not uncommon, and the short-term mortality is not trivial (about one out of every 1,000 people who undergo gastric banding and one out of every 200 people who undergo gastric bypass die within 30 days of the surgery). Thus, the fact remains that the risks and benefits of bariatric surgery must be carefully weighed; those interested in exploring bariatric surgery should engage in a series of conversations with their primary care physicians and bariatric specialists.
While there is no clear consensus on whether it is appropriate to lower the bar for bariatric surgery for diabetic patients, it is certainly a trend, given that its benefits on diabetes are becoming more clearly established. We will be keeping our eyes and ears out for any further advances in this field; in the mean time, researchers are working hard to understand the specific mechanisms by which bariatric surgery improves blood glucose control in hopes of developing drugs that can confer the same benefit. –ST
Biodel's Ultra-Rapid-Acting Insulin Unlikely to Reach Market before Early 2014
Earlier in April, Biodel management updated the timeline for the development of its ultra-rapid-acting insulin candidates. As a reminder, in October 2010 the company's original ultra-rapid-acting insulin candidate Linjeta failed to receive FDA approval (see NewNowNext in diaTribe #27). Consequently, Biodel has chosen not to pursue Linjeta any further; instead, the company is now investigating two other formulations (BIOD-105 and BIOD-107), which should be more tolerable than Linjeta while maintaining similar drug properties (e.g., rate of absorption, duration of effect) and comparable effects of the drug on the body. The two new candidates have only recently entered a phase 1 trial; in the new timeline, the two pivotal phase 3 trials could be initiated before the end of 2012. Accounting for patient recruitment, and assuming a five-month study period for the phase 3 trials, time for data analysis, and a six-month FDA review period, it appears the absolute earliest Biodel's ultra-rapid-acting insulin candidate could be approved would be early 2014.
Unfortunately, no ultra-rapid-acting insulin will likely become available in the near future. In January, the FDA decided not to approve MannKind's ultra-rapid-acting inhalable insulin Afrezza, requesting two additional clinical trials (see NewNowNext in diaTribe #29); as such, Afrezza is unlikely to reach the market until late 2012 at the earliest (assuming timely meetings with the FDA and favorable clinical trial results). Meanwhile, Haloyzyme's PH20, a therapy that aims to bring about faster insulin absorption when mixed with insulin, remains in phase 2 studies. On the bright side, Halozyme recently released promising results from its first pump study, in which it was demonstrated that PH20 sped up insulin absorption and shortened the duration of action of the insulin. All things said, the development of ultra-rapid-acting insulin certainly remains an important need and an essential component of the artificial pancreas. With that in mind, we hope to hear of more focus on this area by large and small companies alike. –VW
XOMA 052, A Novel Therapy for Type 2 Diabetes, Disappoints in Clinical Trial
We've written before about this enticing once-monthly injection that would have improved glycemic control for people with type 2 diabetes and we wanted to give readers an update – albeit a disappointing one. We found out recently that XOMA 052, a novel therapy targeting inflammation in development for type 1 and type 2 diabetes and other indications, failed to produce a significant reduction in blood glucose in a six-month clinical trial in type 2 patients on metformin. This news follows similar disappointing results released in January from three months of treatment in another trial of XOMA 052, calling into question the future of this therapy for type 2 diabetes. The therapy is designed to block the activation of the IL-1 receptor, an important on-switch for inflammation in the body. Interest in this type of therapy has been building since a study in 2007 showed that blocking IL-1 with another drug called anakinra could help lower blood sugar as well as reduce markers of inflammation in type 2 diabetes patients. XOMA 052 is designed to work similarly to anakinra but has a much longer half-life, allowing it to be dosed every four weeks compared to every day for anakinra. There are other similar drugs in development that target the IL-1 receptor, but it remains to be seen if these other therapies are more successful in lowering blood glucose than XOMA 052. On a more positive note, no safety issues were identified in the trial, and the therapy reduced inflammation, improved cholesterol, and improved markers of heart disease risk. The companies developing XOMA 052 have not ruled out continuing to develop the drug for diabetes despite the recent negative results, and have spoken enthusiastically about the possibility of using this therapy to prevent heart disease in people with diabetes or other risk factors. XOMA 52 has shown benefit in a small trial in patients with Behcet's uveitis, an auto-inflammatory eye disease, and the companies have announced plans to enter phase 3 development for this indication. --MY