NewNowNext June 1, 2011
FDA Approves Boehringer Ingelheim and Eli Lilly’s Tradjenta
Earlier this month, the FDA approved the once-daily oral drug Tradjenta (Boehringer Ingelheim and Eli Lilly’s linagliptin) for type 2 diabetes. Tradjenta belongs to the DPP-4 inhibitor drug class, which also includes Merck’s Januvia, Bristol-Myers Squibb/AstraZeneca’s Onglyza, Novartis’ Galvus, and Takeda’s Nesina (the last two of which are currently available only outside the United States). Notably, doctors may perceive Tradjenta as an easier recommendation for people with kidney disease, since it is not primarily cleared by the kidneys as are other members of the drug class. The implication? One dose for everyone, unlike other DPP-4 inhibitors that have more than one dose depending on renal (kidney) health, which means that doctors must periodically test renal function in order to know the proper dosage.
Some background: DPP-4 inhibitors allow the gut hormone GLP-1 to remain longer in the body, which improves glycemic control with a positive side effect profile: less hypoglycemia and less weight gain than many other classes of oral drugs. In the past few years, DPP-4 inhibitors have become increasingly popular, probably because they are once-a-day tablets and have infrequent side effects (e.g., headache, the common cold) and an ever more positive safety profile. While there have been infrequent reports of pancreatitis associated with DPP-4 inhibitors, we increasingly hear the growing safety database associated with the class as a major benefit. Some DPP-4 inhibitors are also available in combination pills with other diabetes drugs, such as metformin (Janumet for Januvia, Kombiglyze for Onglyza, and Eucreas for Galvus), and other combinations are in development – such compounds have even more impressive efficacy data than the non-combo pills, all of which tend to reduce A1c between 0.5% and 0.8%. It is impossible to compare these, however, as there are no head-to-head trials to date among the agents.
Tradjenta is the first diabetes drug to be sold and marketed by Boehringer Ingelheim. The company has another closely-watched diabetes drug in development, an SGLT-2 inhibitor, a new type of oral medications that cause blood glucose to be filtered by the kidneys and lost in the urine (see our Learning Curve in diaTribe #8). Boehringer Ingelheim is studying the use of Tradjenta in combination with its SGLT-2 inhibitor, which would be a new type of combination treatment. We suspect that Bristol-Myers Squibb/AstraZeneca will likely try the same thing with Onglyza and their SGLT-2 inhibitor (called dapagliflozin). DPP-4 inhibitor/SGLT-2 inhibitor combination therapy would likely lower glucose with relatively few side effects and the potential for more significant weight loss. --VW
Insulet Submits Second-Generation OmniPod for FDA Review
Insulet, which makes the OmniPod disposable insulin pump, has submitted a next-generation OmniPod for FDA review. The new pod is approximately 40% smaller than the current version and roughly 25% lighter. The pump system’s handheld device (which Insulet calls a Personal Diabetes Manager or PDM) will be new as well, with a built-in blood glucose meter that uses Abbott’s new FreeStyle strips. The FDA review process for insulin pumps lasts a minimum of 90 days, which means the soonest the FDA would clear the next-generation pod is early August. However, the current FDA requirements for insulin pumps are quite complex (Insulet had to submit a 7,800 page document – in triplicate), and the company has stated that it hopes to have the approval from the FDA by the end of the year. Insulet is still considering how to launch the second-generation device once it is cleared by the FDA. However, the company has discussed one plan that would involve a 6-12 month transition. Under this plan, every current OmniPod user would receive for free the new PDM; the customers who have been using OmniPod the longest would be the first to get the new system). Insulet has not discussed the price of the PDM for people who are new to the OmniPod, but we assume it will be comparable to the price of the original PDM. The new pods will have the same average price as the old pods.
The device has been under regulatory review in the European Union since February, and Insulet hopes to receive EU approval by late June. Meanwhile, Insulet continues to work with Dexcom on a new product that will integrate the second-generation OmniPod with Dexcom’s fourth-generation continuous glucose monitoring system (which Dexcom intends to submit to the FDA as a stand-alone product in late summer). The companies plan to submit their combined pump/CGM to the FDA in the first half of 2012, as we wrote in our update on Dexcom’s fourth-generation system in NewNowNext in diaTribe #31. --JPS
Asante Solutions Receives FDA Clearance and CE Mark Approval for Pearl Insulin Pump
Asante’s Pearl insulin pump has received FDA clearance and CE Mark approval.
In welcome news, Asante Solutions received FDA clearance for its new Pearl insulin pump in mid-May and European approval (the CE Mark) in April. The Pearl is the first fully programmable pump to be cleared by the FDA since the agency instituted new guidelines in 2010 that made the approval process for insulin pumps more stringent. The pump’s design includes several innovative features. First, the Pearl uses prefilled insulin cartridges, which eliminates filling the reservoir and simplifies overall usage. The insulin cartridges are the standard 300-unit “pen-type” cartridges, which are approved for up to seven days in the pump – this would be the only pump to use the cartridges. While the infusion cannula site should be changed every three days, not needing to change the reservoir and infusion set tubing could be a real benefit. Although the use of prefilled insulin cartridges in insulin pumps is not new (back in the day some of Disetronic’s devices included this feature although the pump wasn’t popular due to other detractions), it certainly could make the Pearl a real choice for novice pumpers and a little bit more convenient for experienced users. Despite the 300-unit prefilled cartridge, the Pearl is able to remain small and sleek (3.88" x 1.72" x 0.75") due to Asante's innovative drive mechansism. The Pearl also has a semi-disposable modular design consisting of a permanent controller (with the buttons and display) and a disposable pump body that clip together to form a long, slim unit. The pump body, which contains a battery and all the necessary moving parts, is replaced when the cartridge is empty. This modular design would reduce the high startup cost of buying a pump, and the pump body kits are “pay as you go,” which means a monthly co-pay for those with insurance – this is similar to the Insulet payment model. Additionally, the Pearl has several additional user-friendly features, including occlusion alarms that gradually get louder rather than start at a loud volume, a built-in flashlight (to help identify bubbles in the tubing), and familiar tubing choices that are automatically primed upon attachment. Asante has yet to announce the launch date for the Pearl; for now, the company is focusing on building up its operations and customer support facilities. –KRC
Abbott Receives CE Mark Approval for Its FreeStyle InsuLinx Blood Glucose Meter
Abbott received CE Mark approval for FreeStyle InsuLinx blood glucose meter.
Since receiving CE Mark approval for its FreeStyle InsuLinx in Europe, Abbott has launched the meter in Belgium, France, Germany, the Netherlands, and the United Kingdom. Designed for people with diabetes using mealtime insulin, the meter is Abbott’s first to include a bolus calculator that accounts for fingerstick readings and insulin on board (although the device does not sync up with insulin pumps). Among other data, the InsuLinx stores meter readings, bolus recommendations, pre-/post-meal markers, and carbohydrates. The meter’s USB connectivity allows direct upload to computers and analysis with the FreeStyle Auto-Assist data management software. The Auto-Assist software, which is built into the InsuLinx and is not compatible with previous generations of meters, lets users generate reports and send them to their healthcare providers, and, great news, it is compatible with Mac OS X as well as Microsoft Windows. As a nice touch, InsuLinx users are able to personalize their devices with weekly messages and by uploading a personal photograph. The InsuLinx also features a large, monochrome touch screen, and uses Abbott’s FreeStyle Lite test strips with ZipWik tabs, which make the application of blood easier. Though the InsuLinx is larger than traditional meters, the overall size seems reasonable because the device is thin and light.
In a major win for patients, Abbott has secured reimbursement for the meter in the countries where it was introduced, so it should be available for the same price as the company’s other meters (i.e., FreeStyle, Optium, Precision) for those with coverage. So far, Abbott has not said when it plans to introduce the InsuLinx in the remainder of Europe, nor has the company provided information on the regulatory status of the meter in other regions of the world. --JPS/LV
Medtronic and Bayer to Bring Integrated Products to the US
Medtronic and Bayer have announced that they will partner over the next several years to develop “innovative next-generation diabetes management systems for patients worldwide.” While this is not a new partnership (since 2007, Bayer and Medtronic have offered Bayer’s Contour Link meter that wirelessly connects to Medtronic pumps and CGM devices to users in over 20 countries outside the US), the companies’ intention to make these products available in the US for the first time is exciting news. While few details have been released, we know that Bayer has submitted a meter to the FDA, and we suspect this meter will be compatible with new Medtronic pumps and CGM if it is approved. Bayer and Medtronic plan to eventually deliver integrated products that are smaller, easier to use, and more accurate than current offerings, but few details on timing have been disclosed.
These new developments coincide with the conclusion of a three-year partnership between Medtronic and LifeScan through which the companies offered a LifeScan OneTouch UltraLink meter that wirelessly connected to Medtronic products in the US. Now that the LifeScan-Medtronic contract has been fulfilled, Medtronic will expand its relationship with Bayer while LifeScan will focus on collaborations with fellow J&J subsidiary Animas. While Bayer and Medtronic await approval of an integrated system in the US, LifeScan’s UltraLink will continue to be available to Medtronic users. --JS
Lexicon’s Unique Experimental Medication LX4211 Impresses in Early Trials
When your blood sugar gets too high, don’t you wish you could just filter the sugar out of your blood stream? In fact, along with waste products, the kidneys filter about 180 grams of glucose out of the blood each day, although almost none of that sugar makes it to the toilet. Since our bodies are designed to never waste calories, a special pump works hard in the kidneys to push this filtered sugar back into the blood stream. This pump, which is called the sodium glucose transporter-2 (SGLT-2), is now the target of a new class of investigational diabetes medication called SGLT-2 inhibitors. By turning off the kidneys' glucose pump, this class of investigational medication improves glycemic control by allowing people to urinate excess glucose (see our Learning Curve in diaTribe #8).
There are a number of SGLT-2 inhibitors in development, of which the furthest along is called dapagliflozin. It has been developed through a joint venture between the pharmaceutical companies Bristol-Myers Squibb and AstraZeneca, and it could become available for people with type 2 diabetes by the end of 2011. Another experimental medication that blocks SGLT-2 called LX4211 lags years behind dapagliflozin, but has some particularly interesting attributes. LX4211, which is being developed by Texas-based Lexicon Pharmaceuticals, is unique because it blocks not only SGLT-2, but also a second glucose pump called SGLT-1 that is found in the gut (and also in the kidneys to a lesser extent). Therefore, LX4211 not only causes the kidney to excrete glucose, but it also has the added benefit of blocking the absorption of glucose in the gut. One longstanding objection of SGLT-1 inhibition is that blocking sugar absorption in the gut could theoretically lead to lots of diarrhea and flatulence because the left-behind sugar could become a feast for gut bacteria. In a similar fashion, there are concerns of yeast infections and other urinary tract infections with SGLT-2 inhibitors. However, in the first small studies of LX4211, neither of these has been an issue. In fact, the left-over sugar in the gut has instead proved to be yet another bonus, because it seems to stimulate the gut to secrete “incretin” hormones like GLP-1 and PYY, which make us feel full, cause weight loss, and stimulate the secretion of insulin. (Several approved diabetes medications like the GLP-1 agonists Byetta and Victoza, and the DPP-4 inhibitors Januvia, Tradjenta, and Onglyza, work by leveraging one or both of these hormones.) In a recent four-week trial in individuals with type 2 diabetes, individuals treated with LX4211 had a 0.76% reduction in A1c and just over four pounds of weight loss beyond placebo (inactive pill). Lexicon expects to initiate a larger 12-week study of LX4211 in June; if recruitment goes smoothly, initial results could be released in the first half of 2012. --MY
Amylin and JDRF Collaborate to Explore Combining Insulin and Symlin in One Injection
Amylin and JDRF will be looking into the possibility of combining Symlin and insulin into one injection.
Earlier this month, Amylin and JDRF entered a partnership to investigate the feasibility of combining Symlin (pramlintide) with insulin in a fixed ratio into one injection and to see how effective it is as a treatment for type 1 diabetes compared to insulin therapy alone. As background, Symlin is an analog of the human hormone amylin, a compound normally produced by healthy pancreases (see Test Drive in diaTribe #2). Amylin and insulin work in tandem to regulate blood glucose levels. Specifically, amylin helps to control the rate at which glucose enters the blood stream immediately following meals, blunts the secretion of glucose by the pancreas, and enhances feelings of fullness. Since individuals with type 1 diabetes do not produce either insulin or amylin, the ideal management of blood sugar levels would involve replacement of both hormones.
However, Symlin’s dosing and side effects have often precluded its use – only a small percentage of people with type 1 diabetes currently use the therapy. As such, Amylin and JDRF are developing studies to assess how well insulin and Symlin work together in a single injection. Bringing these two hormones together would likely more closely represent the natural workings of the pancreas due to the fact that insulin and amylin are used simultaneously in the body to stabilize blood glucose levels; thus, individuals would likely be able to remain in the normal glucose range longer. Also, co-formulation would reduce the complexity of daily treatment by eliminating one injection from an individual’s routine. However, there is one potential drawback – insulin and Symlin cannot be titrated individually in the co-formulation. Thus, for the select few who are willing to forego the convenience of fewer injections, taking insulin and Symlin in separate injections may ultimately still allow for the best control. For practical tips on how to use Symlin, please see our Thinking Like A Pancreas column in diaTribe #20. --KRC/VW
Novo Nordisk's Experimental Basal Insulin Degludec Produces Less Hypoglycemia than Lantus in Recent Study
In a recent study, Novo Nordisk's next-generation basal insulin degludec was found to cause less hypoglycemia than Lantus.
In early May, Novo Nordisk announced the results of a study of its next-generation basal insulin, called degludec, demonstrating that it causes less hypoglycemia than sanofi-aventis' Lantus, the current leading basal insulin. The study was a meta-analysis, a pooling of data from multiple trials comparing degludec with Lantus. In type 2 patients using only basal insulin, degludec caused 17% less overall hypoglycemia and 36% less nocturnal hypoglycemia than Lantus. In all participants (people with type 1 or type 2 diabetes, using either basal insulin alone or in combination with mealtime insulin), people using degludec also experienced 9% less hypoglycemia overall, with 26% less nocturnal hypoglycemia. This lower rate may be attributed to degludec’s very long and even activity profile. As we’ve noted previously, degludec could be available as soon as 2013 in the US and in Europe. A number of different formulations of degludec are also in the works, including a fixed-dose combination of degludec and mealtime insulin (55% degludec and 45% NovoLog), and a combination of degludec and the GLP-1 analog Victoza. –MY
D. Medical Gains FDA Clearance for Universal Infusion Set
D. Medical's Spring Universal Infusion Set has been cleared by the FDA.
After almost 18 months of review at the FDA, D. Medical’s subsidiary Spring-Set Health Solutions has received clearance for its Spring Universal Infusion Set. More recently, the company also received a medical device license from Health Canada. In addition to its “universal fit,” which applies to any Luer-Lok pump, the Spring Universal Infusion Set has several attractive innovative features, including: a "Detach-Detect" mechanism that alerts users when their sets are detached from the body; a hidden, auto-retractable 28-gauge needle with a trocar tip designed to reduce pain and scarring and to minimize cannula bending potential; and a 360°-connector. By simplfying the insertion process to a one-touch button push, the Spring Universal Infusion Set allows more users to properly insert the sets on their first try. D. Medical intends to make the infusion sets available in the US and Canada in the next few months. --JS
Diamyd's GAD65 Vaccine for New-Onset Type 1 Diabetes Disappoints in Clinical Trial
In recent news, Diamyd Medical released disappointing results from its European phase 3 trial of its self-titled Diamyd GAD65 vaccine for the treatment of new-onset type 1 diabetes. As background, GAD65 is a protein found on beta cells that is thought to be targeted by the immune system in the development of type 1 diabetes. By exposing the immune system to GAD65, the company hopes Diamyd will restore the immune system's ability to recognize GAD65 in a non-destructive manner, thereby slowing or halting further beta cell attack.
Although Diamyd delayed the progression of type 1 diabetes out to 30 months of follow-up in a previous smaller study, data from the 320-participant European trial did not provide as promising an outlook. In the European trial, individuals treated with Diamyd did not show a statistically significant preservation of beta cell function after 15 months of follow-up compared to placebo (inactive injections), although a small positive effect was seen. While these latest results are somewhat discouraging, we hope that the 320-participant US DiaPrevent study and/or extended 30-month follow-up data from the European trial (both expected to be released in 2012) will demonstrate some degree of beta cell preservation for individuals with new-onset diabetes. In addition, the Diamyd vaccine is also currently being evaluated in a separate, smaller clinical trial as a potential treatment to prevent type 1 diabetes from developing in high-risk individuals. --VW/OB