Memorandum

Medtronic and Aetna launch two-year pilot program testing insulin pumps in type 2 diabetes; competitive landscape overview – March 5, 2014

Executive Highlights

  • Medtronic and Aetna will conduct a two-year pilot program testing insulin pumps in up to 300 patients with uncontrolled type 2 diabetes (A1c >8%).
  • This continues an increasing trend of payer-company pilots that we expect to accelerate in diabetes technology in the coming years.
  • Companies developing insulin delivery devices targeted at type 2 diabetes include Valeritas, CeQur, J&J, Insulet, Debiotech, and potentially BD.

Medtronic announced a new pilot program on Monday with Aetna to use insulin pumps in up to 300 fully insured members with uncontrolled type 2 diabetes (A1c >8%). Participants will receive a MiniMed Revel insulin pump and considerable support: targeted education, case management, and enrollment in Medtronic's Getting2Goal program (to help simplify insulin pump therapy) and StartRight (an onboarding program to help with the transition to insulin pump therapy). The program is expected to run for two years, and the companies will evaluate success based on glucose control, overall health outcomes, and medical costs (e.g., reduced ER visits and hospital stays). Information gathered from the program is also expected to help HCPs more easily identify and support type 2s who can benefit most from pump therapy – the question of optimal type 2 pump candidates has been long debated. (Many believe  it is the same criteria as type 1, though we think this sentiment will change as more differentiated devices come to market.) Unfortunately, the Medtronic/Aetna pilot program will not include CGM, something we hope to see in future pilots in type 2 diabetes; that said, given the higher starting A1c, showing differentiation should not be a problem. We wish that patients in this trial were using CGM to assess “time in zone” as well as A1c; this is missing the forest for the trees in our view, but we suspect Aetna didn’t want to fund the CGM expense.

We were encouraged to see this announcement, since about 50% of type 2s are not at goal, and many dislike insulin injections. (Roper Starch reported in 2006 that 89% of type 2s who use insulin do not inject it outside the home) Pumps for type 2 diabetes occupy a small niche of the market (<3% penetration by our estimates); patients on Valeritas’ V-Go have appeared to have done very well, and Cequr and others are clearly interested in this segment. From our view, there are more than enough patients, given the skyrocketing type 2 numbers, and more patients will ultimately be going on insulin even if the oral drugs are delaying that move.  Certainly, the MiniMed Revel is a more full-featured, comprehensive pump than the V-Go, which will appeal to a later-stage type 2 patient that needs higher basal rates and greater customization. We wonder if Medtronic has plans to develop a simplified type 2 pump, or if it will focus on leveraging its existing type 1-focused pumps for later-stage type 2s. In our view, the simple/complex type 2 pump discussion really boils down to individualizing therapy and providing patients and HCPs with more options. See a complete review below of the in-development delivery devices that we are aware of.

What follows is a discussion of the barriers to more pump use in type 2 diabetes, a review of why we expect to see many more payer/industry partnerships, and an assessment  of the competitive landscape for insulin delivery in type 2 diabetes. Our appendix has recent conference talks from Drs. Phillip Raskin and Bruce Bode on insulin pumps in type 2 diabetes.

  • Aetna will use claims data to identify patients who are fit to enroll in the pilot program. Aetna members enrolled in the pilot will have to be eligible according to Aetna policy, have an A1c > 8%, and express a desire for improved glucose control (presumably, the majority of patients would fit the latter). Aetna will notify doctors about the program, and if a doctor and member decide to use a Medtronic insulin pump, the patient will be enrolled in the pilot and the associated educational programs.
  • As a reminder, Medtronic is still manufacturing the Paradigm Revel System, as the MiniMed 530G is not indicated for pediatrics. Additionally, the MiniMed 530G is not available to those in special situations where a patient does not have CGM coverage (e.g., Medicare). The MiniMed 530G is sold as a “system,” meaning those who want it must get the Enlite CGM and Bayer Contour Next Link meter. Those not interested in CGM or loyal Dexcom users would instead get the Paradigm Revel pump.
  • Three key barriers have deterred broader use of pumps in type 2 diabetes:
    • Clinical Inertia – Doctors have not been accustomed to using pumps in this fashion. In his Clinical DTM talk below, Dr. Bode cited this factor as the major roadblock.
    • Reimbursement and clinical data – Clinicians we’ve spoken to say that payers usually reject requests automatically to use pumps in type 2 diabetes. Appeals require letters of medical necessity, which few clinicians have time for. Notably, the VA does cover pumps in type 2 diabetes, but it is an exception rather than the rule.
    • Patient perceptions – Wearing a device on the body is a big leap for any patient. Even in type 1, where reimbursement is generally very good for pumps, only ~30% of US type 1s wear a pump. This has increased over time as pumps have become more user friendly. Some of this resistance surely stems from a psychological wall of wearing a device. In addition, type 2 diabetes is much more forgiving than type 1, meaning missed doses of insulin do not exact the same physical and emotional toll. With less motivation, it’s even more critical that type 2 products are very low-hassle.
  • The Medtronic collaboration reflects broader trends in the diabetes marketplace (e.g., on the technology side, Telcare, WellDoc, and Glooko have all focused on payer/employer partnerships with their respective devices). We believe this trend will continue in light of the following:
    • Innovations in diabetes technology move faster than scientific literature can prove their value. Pilots allow companies to clinically validate their products in more real-world settings.
    • Conducting RCTs in technology has historically been a challenge, as the parameters of the trial are much different than in drugs (e.g., required support and education, inability to blind, etc.).
    • There is often a win-win to pilot projects, as companies with devices can prove their products are effective, while payers can gather credible data, sample the device, and invest a minimal amount of capital in gathering all the information. For service-oriented solutions that don’t focus on a device (e.g., Omada Health, DPS Health), the challenges with payer partnerships are somewhat greater – payers can mimic the service solutions by developing their own proprietary systems, thereby circumventing the need to work directly with the innovator.
    • Healthcare purchasing is becoming more value- and outcome-based, which increasingly mandates that products improve clinical outcomes.

Overview of Pumps in Type 2 Diabetes

  • A presentation at ATTD 2014 covered the research design/methods of OpT2mise, a much awaited Medtronic-supported RCT comparing insulin pump therapy to MDI in patients with type 2 diabetes (ClinicalTrials.gov Identifier: NCT01182493). The 400-patient, 37-center, six-month study has completed enrollment and Medtronic is working on publishing the data in the next several months. (For context, this represents over three years to complete the study, as it began in December 2010.)
    • Although the two large RCTs on pumps in type 2 have not shown a benefit in terms of A1c, Dr. Bruce Bode expressed faith in this trial at Clinical DTM 2012. He noted that OpT2mise has improved upon earlier trials by testing the benefit of pumps in MDI failures (A1cs of 8-12%). This is of course a much more real-world and logical population to show the benefits of pump therapy, especially given the expense these patients pose on the healthcare system.
  • At Clinical DTM 2012, Dr. Bruce Bode estimated that ~50,000-100,000 patients with type 2 diabetes are on insulin pumps in the US. Assuming that ~4-5 million type 2s in the US are on daily rapid-acting insulin, that equates to <3% penetration.
  • Data has suggested patients with type 2 diabetes can do well with just one basal rate per day. In an open-label, multi-center pilot study (Frias et al., J Diabetes Sci Technol 2011), 21 insulin-pump-naïve patients (MDI at baseline) initiated insulin pump therapy. After 16 weeks, mean A1c reduction was 1.1% from a baseline of 8.4%. Equally important, at study end, 80% of patients (n=17) were treated with one daily basal rate, while 10% (n=2) were treated with two daily basal rates, and the remaining 10% (n=2) were treated with greater than two daily basal rates. Though patient populations obviously differ greatly between studies, this lends support for simpler type 2 delivery devices with a single daily basal rate. That said, there are enough patients not at goal that more customized  pumps would have an ample market (e.g., if ~20% of 4-5 million patients need more than one daily basal rate, that’s still ~900,000 patients).  
  • An online survey of 502 type 1 and type 2 insulin users found that over 50% of responders skip injections occasionally and 20% omit doses regularly (Peyrot et al., Diabetes Care 2010). In a separate survey, 57% of responders with type 2 diabetes currently not taking insulin expressed anxiety over starting insulin therapy for several reasons, including concerns about correct dosing, embarrassment over taking insulin, and fear of injection pain (for more details, please see our AACE 2012 report). We think these data speak to the dire need for insulin delivery alternatives that are more convenient and more discreet.

Overview of Insulin Delivery Devices for Type 2 Diabetes

  • There are a variety of type 2-specific insulin delivery devices either on the market or in development. This list is not exhaustive.

Pump

Details

Last Major Update

Last Coverage

Valeritas V-Go

-24-hour wear
-Fully disposable
-20, 30, 40-unit basal rate
-2-unit boluses (36 units max)
-Reservoir max: 76 units

Plans to go public in 2H14; 13,777 prescriptions for V-Go in 4Q13, representing growth of 19% month-over-month and 877% year-over-year.

JPM 2014

CeQur PaQ

-Three-day wear
-Combination disposable/reusable
-16, 20, 24, 32, 40, 50, 60-unit basal options
-2-unit boluses
-Reservoir max: 330 units

Positive CGM and ease of use data presented at ATTD. CE Marked in November 2012.

ATTD 2014

J&J/Calibra Finesse

-Three-day wear
-Fully disposable
-Bolus-only (1 or 2 units)
-Reservoir max: 200 units
 

Commencing additional clinical studies to prepare for launch. (We could not find any on ClinicalTrials.gov)

 

J&J 2Q13

Insulet OmniPod for use with Lilly’s U500 insulin

-Three day wear
-Disposable pod, reusable PDM controller
-Customizable basal/bolus
-Reservoir max: 200 units

FDA 510(k) submission expected in late 2014

Insulet 4Q13

Debiotech JewelPump2

-Three-day wear
-Disposable patch pump, reusable smartphone controller
-Customizable basal/bolus
-Reservoir max: 800 units

Debuted JewelPump2 at ATTD 2014. Original Jewel is in preparation for CE marking.

Debut at ATTD 2014

BD

Interest in smaller patch pumps targeting MDIs.

“Investing in technology internally”

JPM 2014

 

Close Concerns Questions

Q: What is the biggest barrier to greater use of insulin pumps in type 2 diabetes? If the NIH donated $1 million to this very problem tomorrow, what single initiative would most move the needle?

Q: Will Medtronic pursue a simplified pump for type 2 diabetes in the US and Europe?

Q: What evidence will payers require to provide more robust reimbursement for pumps in type 2 diabetes?

Q: Who is the ideal type 2 patient for the various insulin delivery devices mentioned above?

Q: What role can professional societies play in shifting clinical perceptions about pumps in type 2 diabetes?

Here is some previous Close Concerns coverage on pumps in type 2 patients.  

Appendix 1: ADA 2013

Use In Type 2 Diabetes

Dr. Phillip Raskin (The University of Texas Southwestern Medical Center, Dallas) began this packed session (competing with the ADA President’s session) with a review of insulin pumps in type 2 diabetes (though we note he spent a decent portion of the talk on type 1s). He said that “there isn’t much good clinical trial data about use of pumps in type 2 diabetes.” Indeed, he only covered three prospective, randomized controlled trials comparing MDI to pumps in type 2 diabetes (Saudek et al., JAMA 1996; Raskin et al., Diabetes Care 2003; and Herman et al., Diabetes Care 2005). A1c declines were comparable between MDI and pumps, though patients preferred pump therapy (“patients love this insulin pump therapy more than injections”). He last reviewed Medicare’s extensive criteria for reimbursing pumps in type 2 diabetes – interestingly, these were based on his group’s 2005 study (“I don’t like it myself”). Overall, Dr. Raskin concluded that a pump is probably a reasonable treatment option in type 2 patients who are NOT on Medicare; it has better patient acceptability than MDI; and “this is the truth: it is way more expensive than injections” (~$2,000 a year more to use a pump than MDI). We were struck by the dearth of good data on pumps in type 2, much of it old – we look forward to the reporting of Medtronic’s ongoing, very large OpT2Mise trial of pumps in type 2 diabetes (ClinicalTrials.gov Identifier: NCT01182493).

  • Dr. Raskin covered three randomized controlled trials comparing pumps to MDI in type 2 diabetes (“When you evaluate data, nothing beats the randomized controlled trial”).
    • The first was Saudek et al.’s (JAMA 1996) comparison of the MiniMed implantable pump to MDI in 121 type 2 patients. Baseline A1c of 8.8% declined by 1.5% for those on the pump, comparable to the 1.4% decline (baseline: 8.9%) in those on MDI. The pump group used less insulin and saw less weight gain over the course of the 12-month study.
    • Dr. Raskin also covered his own 2003 study published in Diabetes Care. He studied 127 type 2s, randomizing them to the implantable MiniMed 507C pump or MDI (aspart plus NPH). Declines in A1c were similar: -0.6 in the pump group (baseline: 8.2%) and -0.5% in the MDI group (baseline 8.0%). There was no difference in the frequency of hypoglycemia, though quality of life was higher in the pump group
    • Last was Herman et al.’s influential 2005 Diabetes Care study in 107 patients with type 2 diabetes. Patients were 60 years or older in this two center, randomized, 12-month study comparing pumps (lispro in MiniMed 508 pump) to MDI (preprandial lispro vs. glargine). There was no difference in A1c between the groups. Disappointingly, he noted, “As a result of our study, Medicare will not pay for insulin pumps or pump supplies for individuals with type 2 diabetes. Thank you very much, I don’t like it myself.”
  • Dr. Raskin also covered a few uncontrolled trials comparing pump therapy to MDI in type 2 diabetes (“not the trial we want to use”). Lenhard and Maser (ADA 2001) saw no decline in A1c (baseline 7.6%) in 12 MDI patients switched to a pump. On the other hand, Frias et al. (JDST 2011) observed a 1.2% decline in A1c (baseline: 8.3%) in 21 MDI patients (100 units of insulin per day) switched to a once-daily basal rate in a pump and boluses at each meal over 16 weeks. Leinung et al. (Endocrine Practice 2013) studied 57 type 2s via retrospective chart review, finding a 1% decline in A1c over 16 weeks (baseline 8.7%). Insulin dose also declined.
  • A slide displayed Medicare’s long-list of criteria for pump therapy in type 2 diabetes. The first and arguably most important one is fasting C-peptide <110% of the lab’s lower limit of normal. The full criteria can be found at http://www.cms.gov/medicare-coverage.
  • Dr. Raskin reviewed criteria for selecting type 2 patients for insulin pumps, noting that it’s “pretty much the same as type 1 diabetes.” Factors include suboptimal glycemic control, motivation to pursue intensive therapy, willingness and ability to perform frequent SMBG, sufficient education and ability, adequate psychological stability, appropriate financial resources, and skilled medical staff available.
  • Said Dr. Raskin, “A pump is not magical. It takes work. People need to be motivated to do this. They need to have a brain, to be frank.” Contraindications include hypoglycemia unawareness, counterregulatory unresponsiveness (neither common in type 2 diabetes), age (older, complications), and medical reasons (short life expectancy, malignancy, etc.).

Appendix 2: Clinical DTM 2012

Does Insulin Pump Therapy Have A Role In Type 2 Diabetes?

Dr. Bruce Bode (Atlanta Diabetes Associates, Atlanta, GA) gave a comprehensive presentation on pumps in type 2, including the therapy’s rationale, a literature review, the near-term product pipeline, estimated current market size (50,000-100,000 patients), and what we can expect on the clinical trial front. Although the two large RCTs on pumps in type 2 have not shown a benefit, Dr. Bode has faith that Medtronic’s OpT2mise trial will change that – the study has improved upon earlier trials by testing the benefit of pumps in MDI failures (A1cs of 8-12%). Dr. Bode made it clear that pumps have numerous benefits in type 2s, and the introduction of simpler devices (e.g., Valeritas’ V-Go) should dramatically expand the market. On a separate but related note, we also learned from Dr. Bode that Tandem will be launched at ADA this year and the company has future plans to build a 500-unit (!) reservoir – we wonder if this would be accompanied by a simpler design for type 2s. Dr. Bode also mentioned that U200 pens will be coming out this fall and U300 for Lantus will arrive next year.

  • The biggest problem in treating type 2s with insulin is the reluctance of providers to start insulin. Much of this stems from lack of training – many providers never received the proper training to start people on insulin. Even Dr. Bode’s fellows in endocrinology did not know how initiate insulin therapy. Dr. Bode noted that the launch of Lantus “helped a lot” and explained that insulin is cheaper than most orals.
  • There are numerous benefits of pump therapy for type 2s: improved glycemic control, reduced glucose toxicity, beta cell preservation, enhanced quality of life, improved patient satisfaction, and greater ease of management. Additionally, given that 89% of type 2s do not inject insulin outside the home (Roper Starch 2006), Dr. Bode believes that patients need more options to discreetly take their insulin.
  • Dr. Bode estimates that there are between 50,000 and 100,000 type 2 pumpers in the US. Medtronic data from 2008 estimated the type 2 pump market at 37,000 patients (<1% penetration) – according to Dr. Bode, people think it’s easily doubled by now. He also believes that the upcoming dedicated type 2 pumps will increase this number “dramatically.”
  • Pumps for type 2 diabetes must be cost-effective, simple, and most importantly, discreet. Regarding the latter, Dr. Bode reiterated that patients simply don’t inject insulin outside the home. Unfortunately, current pumps (Medtronic, Animas, Insulet, Roche) have been used in type 2 diabetes, but none have been specifically designed for type 2s.   
  • Pump therapy indications are stringent, mostly restricting pumps to insulin deficient type 2s. Patients need an A1c >6.5 or 7%, glycemic excursions, hypoglycemia or hypoglycemia unawareness, and the need for a flexible insulin regiment. Medicare and Aetna have other criteria as well – fasting C-peptide <110% lower limit of normal or <200% lower limit of normal if CrCl <50 ml/min with concurrent FPG <225 mg/dl or beta cell autoantibody positive (+ICA or +GAD antibodies).
  • Two large RCTs comparing pumps to MDI in type 2s have shown no difference in A1c; however, both studies enrolled a suboptimal population and Medtronic’s ongoing OpT2mise trial will be a “definitive trial of pumps in type 2.” Dr. Bode believes the two major RCTs of pumps in type 2 (Raskin et al., Diabetes Care 2003 and Herman et al., Diabetes Care 2005) made an important mistake – they did not compare patients failing MDI to pump therapy. Fortunately, Medtronic’s OpT2mise study, examining pump therapy in type 2s with A1cs between 8-12%, will do just that. The 30-center, prospective RCT has a target enrollment of 400-600 patients (160 enrolled thus far) and an estimated primary completion date of December 2012 (clinicaltrials.gov identifier: NCT01182493). We look forward to seeing results as they emerge – certainly, we expect Medtronic will leverage learnings from its highly successful STAR series of trials.
  • Edelman et al., Diabetes Technology and Therapeutics 2010 demonstrated that the majority of type 2s can be controlled on only one basal rate. This 16-week, open-label, multicenter, pilot study initiated insulin pump therapy in 56 insulin pump-naive type 2s. Insulin doses were adjusted to achieve the best control with the simplest insulin regimen. By the end of the trial, 88% of patients were treated with two or fewer daily basal rates, and 80% were on just one daily basal rate at 16 weeks. Mean A1c dropped by 1.2% from a baseline of 8.4%. In patients with a baseline A1c >8.5%, the decline was an impressive 2.1%. Dr. Bode noted that this was also “highly cost effective,” although he conceded that weight did increase by an average of 1.9 kgs.
  • Valeritas’ V-Go was launched in the last month, while the Calibra Finesse is “a good year away.” Dr. Bode highlighted the V-Go’s simplicity (non-mechanical, spring loaded) and high patient satisfaction. Beyond showing a brief picture of the Finesse patch/pen he only mentioned the 1+ year timeline before moving to his conclusion. 
  • Dr. Bode presented two interesting case studies of problematic type 2 pumpers. Case #1 was a 57-year old female with non-alcoholic fatty liver disease and an A1c of 9.2%. After going on a pump, her A1c was still suboptimal at 7.9%. However, she was only averaging 0.9 boluses per day. After putting her on real-time CGM, her A1c declined to 6.3%, she’s had no severe hypoglycemia, and she “loves her CGM.” The key for her was being able to see her glucose excursions on the CGM screen. Case #2 was a 13-year old girl on a pump who continued to gain weight. She had an A1c of 10.4% at diagnosis, a weight of 165 lbs, a height of 63 inches, and a total daily dose of 65 units per day. Pump therapy, once initiated, brought her A1c down to 6.9%; however, her weight had increased to 195 lbs. After Dr. Bode put her on liraglutide (titrated to 1.8 mg/day), her A1c declined to 5.3%, her weight declined to 159 lbs, and she required no basal rate on her pump.

 

--by Adam Brown and Kelly Close