In the Beginning
The first attempt at a “portable” insulin pump was made back in the 1960s by Dr. Arnold Kadish, a private doctor in Beverly Hills, CA. His backpack-sized contraption (pictured below) was in some ways years ahead of its time, ambitiously seeking to act as an artificial pancreas—which is still considered to be the holy grail of this field—through a closed-loop insulin delivery system consisting of an adapted lab Autoanalyser to measure blood glucose, a venous blood circuit and a servo-mechanism pump. While this represented an important proof-of-concept, the system’s size, complexity and its dependance on intravenous access made it impractical.
Things really began to take off in the 1970s, with major progress being made both in developing a practical, portable insulin pump and in validating its cinical use. Prof. John Pickup (King’s College, London) is regarded by many as the father of pump insulin pump therapy for his pioneering work as a research fellow at Guys Hospital, London, where he developing a simple, portable pump (159g—pictured below) for continuous subcutaneous insulin infusion (CSII), providing both basal therapy and a pre-set bolus dose.
Previous pumps had delivered insulin intravenously, which is not suitable for long-term therapy due to the risks of septicaemia and thrombosis. Pickup began clinical use of his device in 1976 and two years later the BMJ published his seminal paper describing CSII for achieving long-term diabetic control.
Around the same time, other groups were also active in this area, giving rise to a little trans-Atlantic rivalry. Perhaps most famously, US-based Dean Kamen (also the inventor of the Segway and the HomeChoice peritoneal dialysis system) developed his AutoSyringe portable drug infusion pump in the mid-1970s, which was initially used for chemotherapy and neonatology and later adapted for insulin therapy.
Insulin Pumps in T1D
Over the years, insulin pumps have continued to improve in terms of size/portability, ease of use, functionality and reliability. Today, pumps for CSII can fit in the palm-of-the-hand and are considered to be the gold standard therapy for type 1 diabetes (T1D) patients. Insulin pumps are a major medical device product segment generating $2.5 billion in annual global sales and growing at 15% per year—making this the second-fastest growth segment in diabetes products.
The benefits of pump therapy for T1D (ie, insulin dependent) patients are well established (eg, Cochrane Review and the DCCT trial). Due to the more physiologically compatible profile of insulin delivery compared with multiple daily injections (MDI), pump therapy leads to better glycemic control (A1C) and fewer hypoglycemic events (eg, NICE review) while offering greater accuracy and patient convenience.
In light of this, most countries offer pump therapy to eligible T1D patients, with utilization rates ranging from around 40% in the US (estimated to grow to 50% by 2018) to an average of 15% in Europe. Ironically, given its role in pioneering pump therapy, the UK is a notable laggard, currently at around only 7%. However, NHS primary care trusts have a statutory obligation to provide funding for insulin pumps and UK clinical guidelines provide clear eligibility criteria for T1D patients having (1) frequent hypos, causing “persistent anxiety” or (2) A1C levels above 8.5%. As awareness of this expands, helped in part by greater patient demand and advocacy by groups such as INPUTdiabetes, UK adoption rates are expected to converge with European norms.
Patch Pumps in T1D
For the past couple of decades, the MiniMed pump (Medtronic) has held a dominant market-share in insulin pumps based on a strong body of clinical evidence on the benefits of pump therapy and through leadership in integrating pumps with continuous glucose monitoring (CGM). However, more recently, traditional tubed pumps like the MiniMed Paradigm, Spirit (Roche) and Animas (J&J) have been severely challenged by smaller, more discreet body-worn “patch pumps”. The market pioneer in this category has been Insulet, which launched in 2005 its first generation patch pump, the OmniPod. A couple of years later, loss-making Insulet completed its IPO on NASDAQ, after reporting 2006 sales of $3.6m with a cost of goods sold of $15.6m (practically shipping dollars with every pump sold). The IPO raised nearly $120m in funds at a market cap of around $385m; on top of nearly $120m in venture funding that had already been invested.
Since its launch eight years ago, OmniPod—until now the only patch pump available for T1D—has captured a 10% share of the overall insulin pump market, with annual sales growth of over 30% in recent years. But this growth has come at a price, as historically Insulet has suffered from a high cost of goods in producing its 3-day disposable pump—which is why in the full year 2012 the company was still loss making (operating loss of around $36m) despite substantial annual sales of over $210m. Nonetheless, investors don’t seem to mind much, giving this loss-making company a current market cap of over $1.7 billion, which values the business at a hefty 8x historical sales. The company and its investors appear to be hopeful that, following the launch earlier this year of its smaller and cheaper (to produce) Gen2 OmniPod, light is finally visible at the end of the long tunnel to profitability.
One of the questions around patch pumps has been what, if any, clinical benefits these devices might provide, beyond mere convenience. Work by Dr Howard Zisser (Sansum Diabetes Research Institute, Santa Barbara, CA) suggests that patch pumps have the potential to offer improved glycemic control over conventional tubed pumps due to the fact that tubed pumps may have to be disconnected for activities such as swimming, bathing, participating in sports or intimate moments, whereas patch pumps are more suitable for such purposes—thereby avoiding the need to disconnect, which has been shown to result in a rise of 1 mg/dl in blood glucose for each minute that insulin delivery is interrupted.
Competition in the patch pump space will soon heat up. Several new entrants—such as the Cellnovo system, the JewelPump from Debiotech and, possibly, the SOLO from Medingo/Roche—are expected to be launched over the next year or so.
Offering the world’s first mobile-connected diabetes pump system, Cellnovo (pictured below) has the potential to be a game-changer—which is why my fund NBGI Ventures has backed the company (where I’m also a board member). Cellnovo integrates a highly accurate, small patch pump; a proprietary color touch-screen controller having an integrated blood glucose test-strip reader and providing a platform for a range of diabetes managment apps; and mobile data connectivity and web-based remote monitoring.
An example of just one useful feature is the automated bolus calculator, which provides bolus dosing recommendations based on values obtained from its integrated blood glucose meter and its food journal app for counting and tracking carbs intake. This type of “automated bolus advisor” provides not only convenience, but has also been shown to improve glycemic control, as demonstrated by the ABACUS study.
Mobile connectivity will automate data collection around important parameters such as insulin dosing, blood glucose values, physical activity and food/carb intake. This will liberate patients from paper-based record-keeping while providing accurate and complete information to physicians and timely alerts to parents and carers.
With its minimalist sleek lines, discreet size, graphical touchscreen interface, and automated wireless connectivity—the Cellnovo system looks more like an aspirational high-end consumer electronic device than a clunky medical product. In a patient-centric world, intuitive usability and appealing aesthetics are important considerations for a device that will be worn and used 24/7.
A recent research report by the investment bank Canaccord Genuity noted that, with its CE marked system and an initial commercial launch expected later in 2013, “Cellnovo is the closest competitor to Insulet”. Of course, as ever, the market—and patients in particular—will be the ultimate arbiter. Meanwhile, we can all take satisfaction in seeing how much these devices have evolved since their early, awkward beginnings fifty years ago, bringing meaningful improvements to the lives of hundreds-of-thousands of patients. The future will surely deliver even greater gains, with promising work already underway in implantable pumps, improved CGM technologies integrated with closed-loop systems (more on these later), prefilled insulin cartridges/pumps, and enhanced integration across a range of wireless devices.