FDA officially announces July 21 Advisory Committee meeting to vote on a non-adjunctive (insulin-dosing) label claim for Dexcom’s G5 CGM– June 1, 2016

Today, the FDA officially announced the July 21 Advisory Committee meeting to discuss and vote on a non-adjunctive (BGM replacement), insulin-dosing label claim for Dexcom’s G5 CGM. The meeting will take place from 8am – 6pm at the Hilton Washington DC North/Gaithersburg (Salons A, B, C, and D). No registration is needed, and those interested in submitting comments or speaking in the open public hearing (1-2pm) should email patricio.garcia@fda.hhs.gov. We’re not sure if the meeting will be webcast, though the room capacity sounds fairly large. It is particularly important from our view given the importance of patients’ perspectives that patients can participate

Like drug advisory committee meetings, the FDA will make background material available on its website no later than two business days before the meeting – we’ll have a preview when that becomes available. It sounds like the Advisory Committee (Clinical Chemistry and Clinical Toxicology Devices Panel) will actually vote on whether to approve the expanded label claim, and we assume both Dexcom and the FDA will present their cases. According to the FDA website, the committee currently has eight members, though only one with significant diabetes expertise (pediatric endocrinologist Dr. Arlan Rosenbloom). The committee’s knowledge of diabetes will be a concern at the meeting, like it is for all diabetes drug advisory committees. But in this case, the risk-benefit balance is especially important – it is easy to focus on the downside (what if the CGM is wrong?), rather than the upside (e.g., opening up Medicare coverage!). It goes without saying from our view that there is significant irony in the fact that the real-world dangers of insulin dosing off inaccurate BGMs are not a focus. We’ll be interested to see how Dexcom and the FDA approach this and what data emerges. We include questions below.

The FDA will host a second Advisory Committee meeting on July 22 to discuss and vote on a 510(k) application for Alere’s Afinion HbA1c Dx point-of-care test to be used for diagnosing diabetes. If cleared, Afinion would be the first point-of-care A1c test cleared for diabetes diagnosis. ADA guidelines specify that only lab tests should be used to diagnose diabetes. This clearance could make it easier and faster to diagnose diabetes and prediabetes right in the clinic, or perhaps other locations like pharmacies. This is critical from our view given the importance of prevention and the ease of use with this test.

• Dexcom first disclosed this meeting on its 1Q16 call in April, and it follows almost 18 months of FDA discussions. A PMA supplement was filed last fall seeking the label update, and we should get a good look at the risk-benefit balance once the FDA posts the meeting materials in July. Mr. Sayer was confident and balanced in his commentary last month, noting the FDA’s concerns about patient safety: “This is such a paradigm shift. They want to make sure we have the public panel and everybody can digest the data.” He emphasized that this panel meeting “could set the tone for all future CGM products,” and certainly, it reinforces Dexcom’s longtime trailblazing leadership at FDA.
  
  • The PMA supplement includes thousands of computer simulations of CGM treatment scenarios (e.g., what if the CGM said X but the meter said Y?), multiple human factors studies, revised labeling language, and a new G5 app for a non-adjunctive label claim.
  • CEO Kevin Sayer said last month that a “very significant post-market study” to support the label will probably be required – this is unfortunate to hear, given how many patients are already dosing off their CGMs and how many patients already view benefit-risk tradeoffs.
• The FDA page hints at the labeling language Dexcom might secure: “...a proposed change in intended use of Dexcom, Inc.’s, Dexcom G5® Mobile Continuous Glucose Monitoring System (CGM) device so that, in addition to tracking and trending interstitial fluid glucose concentrations, patients can use the device as a replacement for their blood glucose meters and make treatment decisions based on the interstitial fluid glucose concentration reported by the CGM.”
  
  • As a reminder, Dexcom received a CE Mark for non-adjunctive CGM labeling in August 2015 (first announced at EASD 2015): “The G5 Mobile System is designed to replace fingerstick blood glucose testing for diabetes treatment decisions.” We wonder how the FDA label might compare to this very expansive wording. Could any real-world data from Europe support Dexcom’s case at the July 21 meeting?
• We remain disappointed that the FDA is requesting this advisory committee, which does not seem like an optimal use of resources, although we understand that there are things we may not understand. While a dosing claim is indeed a big change, it is also true that:
  
  • Current BGMs don’t have an insulin-dosing claim – Insulin-related hypoglycemia and errors cause over 97,000 ED visits each year in the US. How many of these stem from fingerstick meters?
  • Many patients are routinely dosing off their CGMs in the real-world –The label is a formality for this group, and more broadly, we don’t believe patients routinely read long and often highly clinical product labels.
  • CGM is safer than fingersticks on multiple fronts: alarms, trend arrows, and minimizing how often dirty hands affect readings – Adam has had countless false-high fingerstick values of 200+ mg/dl, only because he hadn’t washed his hands (many patients don’t). The only thing that reminds him to wash his hands and re-test is that his CGM reads much lower (80 mg/dl) – a massive discrepancy. Adam has found that in 90%+ of the cases where the meter and CGM differ markedly, it’s the meter that is reading falsely high, and the CGM actually prevents a dangerous overdose of insulin. In that respect, CGM is safer than a fingerstick meter!
  • Dexcom’s MARD at 9.0% is probably more accurate than the low-quality meters many patients receive – particularly those on Medicare who have been switched to lower-quality products after competitive bidding. What a drag! Out of country factories are often hard to check …
  • A dosing claim is a gating factor for Medicare coverage, and these are the patients most in need of CGM – Any potential harms from a dosing claim are arguably outweighed by the benefits of bringing CGM to a hypoglycemia-prone population with long-standing diabetes.
  • A dosing claim could significantly expand the number of patients willing to go on CGM and the number of providers willing to prescribe it – The benefits of expanding CGM access to more patients with this claim arguably outweigh the risk of negative outcomes that could stem from non-adjunctive labeling.
• The news is a potential short-term negative for Medtronic and Abbott, who both have to think about a dosing claim with the MiniMed 670G/Enlite 3 and FreeStyle Libre, respectively. How is FDA viewing those products? We assume Dexcom is further ahead with the FDA than either company on this issue. A dosing claim is particularly critical for Abbott, who has a rough history with the FDA on this topic and ideally wants the same label FreeStyle Libre has in Europe. Can FreeStyle Libre be modified to take calibrations? How does the FreeStyle Libre value proposition change if Abbott has to drop the “No fingersticks” marketing? Will the FDA approve a factory calibrated sensor that doesn’t have an insulin dosing claim? If Abbott gets FreeStyle Libre approved with an adjunctive claim, will it matter from a real-world patient use or uptake perspective? Will Medtronic’s MiniMed 670G/Enlite 3 need a dosing claim? Will either device have an advisory committee meeting?
• Assuming Dexcom ultimately gets the FDA label, we wonder how the FDA will evaluate future products: will it get more comfortable that a dosing claim for CGM is safe, or will it hold all future products to the standard of G4/G5’s accuracy? At JPM, Dexcom positioned the insulin-dosing claim as a competitive barrier to entry for the first time: “We will undoubtedly be the first company to have this label. And we want to set the bar high. You’ve got to have a sensor that performs as well as ours does.”

Close Concerns Questions

Q: How will Dexcom make the case for non-adjunctive CGM labeling? What data can it bring to show that CGM is as safe – or safer – than BGM?

Q: What is FDA’s biggest concern with a replacement claim for CGM? How will Dexcom allay these concerns?

Q: What kind of post-market study will Dexcom have to do?

Q: Will Dexcom’s G5 set the accuracy bar for all other companies to obtain an insulin-dosing label claim?

Q: Will the label expansion apply to G4 with Software 505, or is this only G5? How have these discussion informed Dexcom’s G6 pivotal trial?

Q: Will the replacement claim be an important competitive advantage over Medtronic and Abbott? Could it impact uptake of CGM or providers’ willingness to prescribe?

Q: Will the FDA approve a replacement claim for a factory-calibrated sensor like FreeStyle Libre? [Dexcom has suggested in recent financial updates that the FDA wants to see fingerstick calibrations as a safety check.]

Q: Will FreeStyle Libre (consumer version) have an advisory committee?

Q: Will the MiniMed 670G/Enlite 3 need a non-adjunctive claim? Will the FDA hold an advisory committee meeting to approve the device?

-- by Adam Brown and Kelly Close