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Many people with diabetes fear eye diseases leading to blindness. In diabetic macular edema (DME), the leading cause of blindness among working-age Americans (over 560,000 cases of DME in the US), damaged blood vessels leak fluid into the part of the eye responsible for sharp, straight-ahead vision (the macula), causing blurry vision and ultimately blindness in some cases. Until now, the only approved treatment for DME in the US was laser surgery, which could halt the progression of vision loss but could not reverse the damage (for more information on DME and laser surgery, see new now next in diaTribe #37).
Encouragingly, the FDA approved Lucentis (ranibizumab; manufactured by Roche’s Genentech) for the treatment of DME on August 10, making it the first FDA-approved drug for the condition. The Agency took the advice of a July 26 FDA advisory committee that voted unanimously in favor of its approval. Lucentis is a once-monthly injection directly into the eye and was previously approved for the treatment of DME in Europe and Canada in late 2011 (see new now next in diaTribe #37). In clinical studies, Lucentis improved eyesight for people with DME just one week after the first injection. Over a two-year period, treatment with Lucentis allowed individuals (on average) to read an additional two lines on an eye chart, a meaningful improvement. The drug was generally safe and well-tolerated in these trials; the major downside seems to be its cost – $1,170 per shot, before insurance. Avastin, a similar drug approved for cancer treatment, is already used off-label to treat DME. Although it is significantly cheaper than Lucentis, its safety and effectiveness have not been thoroughly investigated specifically for the treatment of DME. We hope that insurance companies will begin covering Lucentis, which would give more people access to this new treatment. Encouragingly, Genentech has a patient assistance program at www.genentech-access.com/Lucentis for individuals whose insurance does not cover the drug. –AW/JD
Lately, the use of basal insulins (such as Lantus and Levemir) in combination with GLP-1 agonists (such as Byetta, Victoza, and Bydureon) has been garnering increased attention. The combination therapy makes sense for several reasons: 1) the two therapies act in complementary ways to lower blood glucose, meaning that the combination could be more effective than either therapy alone; 2) the weight loss provided by GLP-1 agonists can help reduce (or overcome) the weight gain associated with long-acting insulin therapy; and 3) GLP-1 can be easier to take than short-acting insulin due to its glycemic-dependent nature (meaning it causes less hypoglycemia) and can delay the need for short-acting insulin. In 2011, Byetta and Victoza were approved for use in combination with basal insulin in the US and in Europe; several other GLP-1/basal insulin combinations are also being explored (see our new now next in diaTribe #42).
One such product in development, Novo Nordisk’s IDegLira, combines the company’s ultra-long-acting insulin degludec that has been submitted for approval to regulatory agencies worldwide and Victoza (liraglutide) in a fixed ratio (meaning, if users want to reduce the amount of insulin they wish to inject, the amount of Victoza they receive will also be reduced). On August 14, Novo Nordisk announced results of the phase 3 DUAL I study, which found IDegLira improved participants’ glycemic control significantly more than either degludec or Victoza alone. Over 26 weeks, participants who took IDegLira achieved an average A1c reduction of 1.9%, compared to 1.4% for degludec and 1.3% for Victoza. IDegLira also led to an average weight loss of a little over a pound, an improvement over the average three-pound gain with degludec alone, though those who used Victoza alone lost over six pounds. The next step for IDegLira is the follow-up phase 3 DUAL II study, which is slated to complete toward the end of this year. This schedule keeps IDegLira on track for FDA approval as early as the end of 2013. –AW
As noted in new now next in diaTribe #37, Novo Nordisk announced in October 2011 that it had submitted its two new “next-generation” insulin products for approval in the US. The first product, called degludec, is an ultra-long acting basal insulin. The second product, called degludecPlus, is a fixed-dose combination of basal and mealtime insulin (70% degludec and 30% NovoLog). In late July, the FDA decided to delay an approval decision on degludec and degludecPlus until after a November 8 advisory committee, where a panel of experts will meet and recommend whether FDA should approve the new insulins (FDA does not have to follow the committee’s recommendation, though it typically does). We have heard that the FDA is going to require advisory committees for every new diabetes drug unless there are specific reasons not to, although this news came as a bit of a surprise because it was announced so late in the review process. A possible reason for the delay could be that the FDA is being more cautious due to degludec’s relatively new features, including its potential for more flexible dosing and its extended, 25-hour half-life in the body. We are not aware of any significant safety risks that would hold up the approval process. While the original hope was for both drugs to be approved in the second half of 2012, this likely pushes back the approval timeline to very late this year or, more likely, sometime in 2013. Assuming there are no further delays in the degludec approval process, we do not think this news will materially affect the timeline for IDegLira (a combination of degludec and Victoza) – as a reminder, that is on track for FDA approval by the end of 2013 at the earliest. –AW/AB
Over the course of their lifetimes, roughly half of all people with diabetes develop diabetic neuropathy, which affects the nerves and can cause feelings of numbness and pain, particularly in the extremities. Tight blood glucose control may slow down and possibly reverse underlying nerve damage for some individuals, but not for all. Currently there are two primary medications available to treat the pain and numbness of diabetic neuropathy: Eli Lilly’s treatment for pain (also used for depression), Cymbalta (duloxetine), Pfizer’s treatment for epilepsy, Lyrica (pregabalin), and J&J’s chronic pain medication Nucynta ER (tapentadol), which was approved just this past week to treat neuropathy (we will have more on this late-breaking story in the next issue). In early August, the number of treatment options expanded when NeuroMetrix received FDA clearance for its Sensus Pain Management device for the treatment of chronic intractable pain, including painful diabetic neuropathy (PDN). The new device treats PDN by noninvasively transmitting painless, low frequency electric impulses through the body, a process known as transcutaneous electrical nerve stimulation (TENS). The device is worn on the calf, works at the press of a single button, and is equipped with a rechargeable battery that should last about two weeks based on the recommended once-daily, hour-long treatment sessions. NeuroMetrix intends to launch Sensus at the end of 2012. The company has not released information on how Sensus will be priced, but we hope that insurance companies and Medicare and Medicaid will reimburse the device. Considering how painful neuropathy can be, we’re very keen for more alternatives to treat this complication, and we look forward to Sensus becoming available as a potential alternative for patients. –AW
For several years, we’ve been closely following Insulet’s progress with the FDA to get its smaller second-generation OmniPod approved (see new now next in diaTribe #33). Based on the company’s most recent communication with FDA, we believe approval of the new pump could come in the last few months of 2012. This is approximately a one-year delay from Insulet’s initial expectations (we had seen the product when it was in early development so we have been excited about it for quite awhile!). Part of the reason for the delay is that the current FDA requirements for insulin pumps are quite complex: Insulet had to submit a 7,800-page document – in triplicate! As we understand it, Insulet is currently addressing a single remaining regulatory concern about the pump’s software by adding several confirmation screens (e.g., after setting the clock on the PDM handheld, a user will have to Yes/No confirm that the time was entered correctly). Once the device is approved, current OmniPod users will be upgraded to the new pods and new handheld devices when they reorder supplies. On a very bright note, the upgrade should not add any costs for the patients or their insurance companies. In Europe, the new OmniPod has already launched in the Netherlands, Germany, Austria, and the UK (see new now next in diaTribe #36 for our coverage of the approval) and we anticipate more than 500 patients have the second-gen OmniPod there already.
As a reminder, the new pod is 34% smaller, 25% lighter, and 16% slimmer than the current pod, though it still has the same 200-unit insulin capacity – an impressive manufacturing and engineering achievement. The new pods also have fewer parts than the current OmniPod, which is expected to both reduce costs and improve pod quality – a win-win for both patients and the company. The second-generation OmniPod will also feature a new PDM handheld that includes an expanded communication range (yes!) and use of both correction and meal boluses to calculate insulin on board (the current handheld only takes into account correction boluses for insulin on board – this will be terrific to have this available, as patients have requested it for some time). The PDM will continue to integrate the Abbott FreeStyle meter, though a second handheld is expected to become available sometime in 2013 that will feature an integrated LifeScan meter compatible with Verio strips, giving Insulet pump users the choice of two brands of strips, unlike any other pump offered today. Notably, Dexcom and Insulet will soon begin working on development of a handheld that integrates Dexcom’s new Gen 4 CGM sensor into Insulet’s OmniPod handheld (i.e., the CGM readings will appear on the OmniPod handheld screen, eliminating the need to carry the separate CGM receiver). No timeline has been announced on this device, though we expect it could be available in late 2013 or early 2014. –AB/KC
Wireless, cell phone-enabled, and data-to-the-cloud glucose meters are a new trend in diabetes, evidenced by the recent launch of Sanofi’s iBGStar (see test drive in diaTribe #43) and Telcare’s new meter (see test drive in diaTribe #41). At the American Association of Diabetes Educators Annual Meeting in early August, we got a sneak peek at another exciting product in development: LifeScan’s OneTouch VerioSync. It’s the next system based on the new OneTouch Verio technology platform, which also includes the currently available OneTouch Verio IQ (see test drive in diaTribe #41). The major difference is that the new meter will feature wireless Bluetooth compatibility with the iPhone, allowing blood glucose readings taken on the VerioSync to be sent wirelessly to an iPhone app.
We’ve seen two screen shots of the app and think it looks really sharp – a summary display showed an excellent color-coded graph with percentage of readings in range, blood glucose average, average number of tests per day, icons for logging carbs, activity, and medications, as well as tabs for viewing results. The app also has a section showing blood glucose patterns, one of our favorite aspects of the OneTouch Verio IQ. Like Telcare’s meter and Sanofi’s iBGStar, we most like that the new VerioSync will make transfer and download of data hassle-free. We know patients don’t like manually inputting their numbers into a device and that writing down numbers can actually be hard to do in practice (crazy as that sounds). The device is currently pending FDA approval, and we look forward to giving it a try once it’s launched. –AB
In the quest to develop an artificial pancreas, the development of faster-acting insulin is a crucial component – current rapid-acting insulins do not work nearly as quickly as the insulin secreted by a pancreas in someone without diabetes. Encouragingly, Biodel recently announced that the National Institutes of Health (NIH) awarded it a Small Business Innovation Research grant totaling nearly $600,000 to do further research on developing a highly concentrated ultra-rapid-acting insulin. This would not only work much faster than current insulin, but it would also allow for a smaller insulin reservoir, potentially enabling a smaller pump or making room for a separate pump reservoir for glucagon or another hormone (like Symlin or GLP-1). In addition to its potential use in the artificial pancreas, concentrated ultra-rapid-acting insulin would also greatly improve the treatment options for extremely insulin-resistant patients, who must currently take large doses of insulin. We view the NIH funding as an important endorsement of the company’s research and development efforts.
As a reminder, Biodel previously hit a major setback in its development of an ultra-rapid-acting insulin when the FDA declined to approve its original candidate Linjeta in 2010 due to efficacy and tolerability concerns (see new now next in diaTribe #27). Biodel went back to the drawing board to develop revised formulations of Linjeta that leveraged the ultra-rapid-acting technology, but also improved upon the previous limitations. The company now has a new ultra-rapid-acting insulin candidate, and a 130-patient phase 2 trial is slated to begin in the near future and run until the fall of 2013. Assuming all goes well, the company would then progress to a larger phase 3 trial and be able to submit the drug for FDA approval.
Biodel is also working to develop an improved formulation of glucagon that would not require manually mixing glucagon powder with liquid (known as “reconstitution” – an unfortunate reality of current glucagon kits sold by Eli Lilly and Novo Nordisk). The new glucagon could be used in a simple auto-injector device for severe hypoglycemia (similar to an EpiPen for allergic reactions) or put into a two-hormone pump as part of the artificial pancreas. The company hopes to submit the improved glucagon formulation for FDA approval in early 2014. Several other companies are also working on stabilized glucagon formulations, including Xeris (plans to file for FDA approval of an auto-injector device in late 2013), Latitude (seeking a partner), and others. –AW/AB
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