NewNowNext September 30, 2011

Our First Peek at Bydureon: “Connect, Shake, Inject”

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During our recent trip to Portugal for the 47th Annual Meeting of EASD, we had the chance to see the once-weekly GLP-1 drug Bydureon for the first time since its European approval in June as a treatment for type 2 diabetes (for readers in the EU, please click here to see a picture of Bydureon; the product is not yet approved in the US). As we’ve written previously, unlike the other currently available GLP-1’s Byetta and Victoza, Bydureon requires reconstitution (mixing the drug with a liquid) before its use. Even so, demonstrators at the conference made the process of giving yourself a Bydureon shot look fairly simple. Stressing the cool, memorable phrase “Connect, Shake, Inject,” administering Bydureon includes the following steps:

• Step 1:Connect a vial that contains the drug powder to a syringe that contains the diluent (the liquid that dissolves the drug powder) using a special connector piece.
• Step 2: Inject the diluent in the syringe into the vial with drug powder.
• Step 3: Shake the mixture.
• Step 4: Draw up the mixture into the syringe.
• Step 5: Place the needle onto the syringe.
• Step 6: Inject the drug.

For those that have used an emergency glucagon kit, it’s basically the same idea. Because the components that make up the Bydureon drug are quite large, a larger needle (23 gauge, 7.8 mm long) is used with Bydureon than for glucagon. Victoza, Byetta, and insulin needles can be as small as 32 gauge and 4 mm long. We have heard from Amylin, Eli Lilly, and Alkermes (the companies that are partnering on Bydureon) that a pen for Bydureon is currently under development and that it may be available by late 2012. While we believe that the pen will greatly simplify the process, the needle size used with the pen will likely remain the same. As indicated above, Bydureon is not yet available in the US, but it has been recently resubmitted to the Food and Drug Agency (FDA), placing the drug’s next possible approval date on January 28, 2012. We would be very surprised if the FDA doesn’t grant its approval in early 2012. --BK

JDRF Sponsors $100,000 Prize to Encourage the Development of Glucose-Responsive Insulins

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JDRF is offering a $100,000 prize for innovative ideas on how to develop a glucose-responseive insulin

Earlier this month, JDRF announced that it would award a $100,000 prize for innovative ideas for developing a glucose-responsive insulin. JDRF is simply looking for ideas at this point, and later phases of the competition will further develop the idea for testing in animals and humans. As a reminder, glucose-responsive or glucose-dependent insulin is insulin that works progressively, based on the level of blood glucose. The higher the blood sugar, the more the insulin works – and below a certain level of blood glucose it won’t work at all, minimizing the risk of both hypo- and hyperglycemia. A “solver” looking to win the $100,000 prize will ideally propose an idea for a glucose-responsive insulin that: a) maintains glucose levels between 70 and 110 mg/dl most of the time, with after-meal values rising to no more than 160mg/dl for no longer than an hour; b) prevents overdosing of insulin; and c) reduces the burden of managing diabetes by minimizing human intervention. JDRF is envisioning that a glucose-responsive insulin would ideally only need to be taken once per day (at maximum), would entail no delivery devices like insulin pumps, and would require little to no monitoring of blood glucose. Wow – phenomenal from a patient perspective - development of such an insulin would be an amazing achievement as it would not only bring outstanding glucose control, but it would help alleviate what can be significant stress and hassle that comes with living with diabetes. A glucose responsive insulin could also make insulin therapy a lot safer –according to a 2007 study, insulin was the second most commonly implicated medication in ER visits in people over 65 years old (the first was Warfarin, a blood thinner).

JDRF is working with the crowdsourcing* company InnoCentive to offer the prize to anyone who signs up for the challenge (you can do so free here). Solvers must transfer their exclusive intellectual property rights to JDRF, so we don't necessarily expect this challenge to attract significant attention from pharmaceutical companies and researchers who might be more interested in pursuing the commercial route themselves, although the $100,000 is just a starting point for JDRF grants – there is more money available for further development.

JDRF has already sponsored industry to develop a glucose-responsive insulin. But with this prize, its goal is to attract new people and approaches to the table. Fresh ideas have certainly helped with artificial pancreas research, an area that has made significant progress in the past five years. Indeed, many of the best researchers and most novel algorithms have come from other fields like chemical engineering, applied mechanics, computational neuroscience, and nuclear physics.

As you might expect, there is also interest in developing glucose-responsive insulin among pharmaceutical companies. In late 2010, Merck purchased Smart Cells Inc., a small Massachusetts-based company (funded in part by JDRF) that is developing a glucose-responsive insulin product aptly named SmartInsulin (for more information, see NewNowNext in diaTribe #29). As we understand it, this compound is still in animal testing. We also believe that Novo Nordisk is working on a glucose-responsive insulin, and undoubtedly other ambitious pharmaceutical companies are as well. --AB/KC

*Crowdsourcing asks an undefined, large group of people (a crowd) to solve a problem or complete a task. In the case of Innocentive, organizations can post challenges or problems and “Solvers” can log on to the site (InnoCentive currently has 250,000 registered solvers from 200 countries) and submit solutions. In the past, Eli Lilly, Roche, NASA, and Procter & Gamble have all posted on the site. Since 2001, over 1,300 challenges have been posted with over $28 million in awards offered – according to the company, the average success rate is 50%. Awards range from $5,000 to $1 million based on the complexity of the problem.

Insulet’s Second-Generation OmniPod Receives European Approval

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Insulet recently announced that its second-generation OmniPod had received approval in Europe. Compared to the first-generation OmniPod, the new pod is approximately 40% smaller and 25% lighter – wow! Insulet will launch this second-gen pod in select European countries later this year, and Insulet remains hopeful for a US approval by the end of 2011. At EASD, we had the opportunity to see the new OmniPod for the first time. Overall, we were extremely impressed with how much smaller and thinner it was, while still holding just as much insulin - 200 units. Although we haven’t yet tested the new product, based on its size and weight alone, we believe it could expand Insulet’s market share and maybe even bring new pumpers into the fold. Anything that makes technology less intrusive – or, in this case, less bulky – has that potential. Insulet and Dexcom are also continuing to work on an integrated pump/CGM product that will use the second-generation OmniPod and Dexcom’s fourth-generation sensor. The companies are aiming to submit the product to the FDA in the first half of 2012, placing a possible approval date in late 2012. While we are disappointed this was delayed (see our NewNowNext in diaTribe issue #29), we are happy that the integrated product will have both the most updated sensor as well as newest pod. --AB/KC

Cellnovo’s Patch Pump Gains European Approval and Will Use Recently FDA-Approved LifeScan Verio Test Strips

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At EASD, Cellnovo announced that it had received approval in Europe for its new insulin patch pump. It will be launched soon in the UK, and its submission to the FDA is expected by the end of the year — meaning that approval in the US could come as early as 2012. However, the FDA has delayed the approval of a variety of other pumps, such as Medtronic’s Veo (available in 50 countries around the world since 2009) and Tandem’s t:slim, so it’s unclear how soon this patch pump will become available in the US.

For those unfamiliar with Cellnovo, the company’s product is different from other pumps on the market. The pump is worn on the body (like Insulet’s OmniPod), uses a very short infusion set (similar to a standard insulin pump infusion set, but only about four inches long – unlike Insulet, which does not use infusion sets), and communicates wirelessly to a handheld touch-screen controller. Users will get two reusable pumps so that one can be worn while the other is recharging. The pump also has a built-in accelerometer, which allows it to loosely monitor a user’s activity levels.

Cellnovo’s pump is controlled by an iPhone-like handset, a definite departure from some of the more utilitarian insulin pumps that are currently on the market. Similar to Insulet’s OmniPod, the handset integrates a blood glucose meter and displays and stores blood glucose and insulin delivery data. We also learned during EASD that the integrated blood glucose meter will use LifeScan’s new Verio test strips, which are reportedly some of the most accurate strips on the market. Verio was approved by the FDA in mid-September.

Besides the touch-screen controller, what is new about Cellnovo’s pump is the handset’s mobile capabilities. Every time it enters “sleep” mode (usually after three minutes of non-activity), the handset automatically transmits information (blood glucose, activity, pump, food) to an online portal, “Cellnovo Secure,” where the patient and healthcare providers can view it. The automatic data transfer occurs via a mobile phone network; there is no patient involvement and no cables. We know first hand how much of a hassle data downloading can be, and we appreciate that this pump tries to address that issue. As we understand it, the cost of mobile data will be bundled into the initial pump price.

Manufacturing insulin pumps is definitely challenging, so we’ll be interested to hear more about this one as it begins selling in Europe this year. For now, we’ll stay tuned for more on its progression through the FDA. --AB

Tradjenta receives approval Europe

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In late August, the European Commission approved Boehringer Ingelheim/Eli Lilly’s DPP-4 inhibitor, Tradjenta, for type 2 diabetes. Tradjenta (also known as Trajenta in the EU) is a member of the same class of drugs as Januvia, Galvus (EU only) and Onglyza. As a reminder, the drug was approved in June in the US (for more information, see NewNowNext in diaTribe #33). Tradjenta is unique in that it comes in only one dose and does not require dose adjustment for those with impaired kidney function. Given that approximately 50% of people with type 2 diabetes have some form of chronic kidney disease, Tradjenta could make doctors and patients lives a little bit easier by eliminating dose confusion. --DZ/AB

Vivus to Resubmit Weight-Loss Drug Qnexa to the FDA

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In exciting news, Vivus announced that it intends to resubmit its weight-loss drug Qnexa to the FDA for review by the end of October. As a reminder, in October 2010, the FDA chose not to approve the medication because of concerns over potential long-term safety issues, including increased cardiovascular risk (due to a slightly increased heart rate with Qnexa) and teratogenicity (risk for birth defects). For more details on the FDA’s decision, please see our NewNowNext in diaTribe #26. Following recent discussions with the FDA, Vivus and the agency have agreed on a plan that will allow the company to resubmit the drug for approval in men and women without child-bearing potential who are either obese or overweight with one or more comorbidities (i.e. diabetes, high cholesterol, high blood pressure) – an estimated 80 million adults in the US. The FDA will host a meeting in early 2012 to discuss the benefits and risks of Qnexa in this population, and is expected to make a decision on whether or not to approve the drug by April 2012. Meanwhile, an assessment of the birth-defect risk of topiramate (one of the two components of Qnexa) is ongoing; if the results show no increased risk, Vivus plans to resubmit Qnexa to the FDA in late 2012 for approval in a much larger population of people, which will include women of child-bearing potential. We view this news as encouraging. While diet and exercise should remain core to weight management, medications like Qnexa could become important tools for those struggling to manage their weight through lifestyle efforts alone. --VW

Orexigen’s Contrave Back in Development!

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If you’ve been following our coverage of Orexigen’s obesity drug, Contrave, you’re likely aware that it has been through a regulatory rollercoaster over the past few months. After a committee of independent experts advised the FDA to approve the drug, the agency chose not to approve Contrave and laid out extremely burdensome requirements for approval, including an “outcomes trial” that would involve tracking cardiovascular events in 60,000-100,000 patients (see NewNowNext in diaTribe #34). The company halted development of Contrave and was uncertain whether it would have the financial capabilities to fulfill FDA’s demands. However, this past month, the FDA reversed its previous stance and offered Orexigen a clear, more feasible, and much less burdensome path to approval for Contrave. Specifically, the agency eased its criteria for the outcomes study and is allowing Orexigen to resubmit Contrave to the FDA based on interim results of the outcomes trial. Therefore, if results are positive from the study, Orexigen could resubmit Contrave by early 2014, which would position it for another FDA decision (and potential approval) before the end of the 2014. We expect to hear a more concrete timeline from Orexigen after it finalizes the details of the outcomes study with the FDA in the coming months. Overall, we are very encouraged by the FDA’s willingness to re-consider its previous decisions and hope this signals a greater shift within the organization toward encouraging the development of obesity drugs. --ST

Novo Nordisk receives approval for new FlexTouch Pen in Europe

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Although insulin pens don’t often grab headlines as much as other diabetes devices, we were glad to hear news about Novo Nordisk’s FlexTouch pen earlier this summer. The pen received European approval in July and has been submitted for approval in the US. What’s newsworthy is the pen’s novel delivery mechanism: the FlexTouch uses an “easy-touch” button to deliver insulin, which according to Novo Nordisk, requires very little force to inject the insulin. We hope this will represent an improvement over current pens that rely on the variable force of a user’s thumb to push the button and deliver the insulin. The pen will also provide an audible click when the injection has completed, informing users when their full insulin dose has been given. We know that injecting insulin is not easy, even with the best pens, and we love that Novo Nordisk is trying to soften the sting. We look forward to hearing more about the new pen, especially once it gains approval in the US. --DZ/AB