FDA approves Bydureon BCise, new autoinjector for AZ’s exenatide once-weekly – October 23, 2017

Executive Highlights

  • AZ announced this morning that the FDA has approved a new autoinjector for GLP-1 agonist Bydureon (exenatide once-weekly) under brand name Bydureon BCise (a play on “device” and “precise”). This regulatory decision comes on time with the expected 2H17. The autoinjector has also been accepted for active review by the EMA (again, on track with the 2H17 timeline).
  • US launch of Bydureon BCise is slated for 1Q18, and AZ management anticipates parity pricing to the current dual chamber Bydureon Pen. We’re enormously excited for this product to be in patient hands, especially if this cost strategy is carried through to promote broader accessibility. Bydureon BCise offers patient-friendly dose administration, eliminating the need for a lengthy mixing/tapping process to create an aqueous exenatide solution prior to injection. It also comes with a hidden needle, and a viewing window that allows patients to see inside for confirmation that they’ve received the medication.
  • We were fortunate to speak with AZ’s Executive Director for Diabetes Ms. Sarah Walters and with VP of US Medical Affairs Dr. Jim McDermott. Both leaders acknowledged that while exenatide has well-known efficacy among diabetes providers, ease of administration is also a vital component from the patient perspective – this was missing when the only available options for Bydureon were single-dose reconstitution kits and the dual chamber pen, and Bydureon BCise fills this very important gap. The autoinjector has been highly-anticipated, and we imagine it could meaningfully boost volume/sales for AZ’s Bydureon business in 2018.
  • On a separate but related note, Dr. McDermott highlighted recent label updates for Bydureon and for AZ’s SGLT-2 inhibitor Farxiga (dapagliflozin) to include data from DURATION-8. AZ is now the first company to have positive results on GLP-1 agonist + SGLT-2 inhibitor co-administration on both treatment labels.

This morning, AZ announced the FDA-approval of Bydureon BCise, a patient-friendly autoinjector for once-weekly GLP-1 agonist exenatide. The decision comes on time with the expected 2H17, and US launch is slated for 1Q18 (we’re pleased to see a quick turnaround). This product is a highly-anticipated addition to the Bydureon franchise. Previously, the only available methods of administration were single-dose reconstitution kits and a multi-use dual chamber pen, which still required a lengthy mixing and tapping process to create an aqueous solution prior to injection. As AZ’s Executive Director for Diabetes Ms. Sarah Walters put it, patients/providers need three things from a diabetes therapy: (i) to get in control, (ii) to stay in control, and (iii) an easy-to-use device. With this newly-approved autoinjector, Bydureon now fulfills that last criterion, making it simple and straightforward to take an exenatide dose every week. AZ’s VP of US Medical Affairs Dr. Jim McDermott highlighted other key advantages to Bydureon BCise as well: The autoinjector comes with a hidden needle (making patients more comfortable), and people can watch a plunger inside the device for confirmation that they have received the medication. Bydureon BC uses the same microsphere technology underlying the reconstitution kits and dual chamber pen, but will save people time in the real world, and ultimately lessens the burden of injection with a more patient-friendly design. Dr. McDermott characterized the patient-friendliness as three easy steps – mix, unlock, inject. The new autoinjector has been developed with patient/provider feedback in mind, which we think is a very smart strategy, one that will aid commercial success. As far as specific points of feedback collected, Ms. Walters and Dr. McDermott listed a hidden/non-exposed needle (“very important from the patient perspective”), an easier-to-use device (“this is exactly what providers have been asking for”), and a product that facilitates patients starting and staying on therapy (overcoming initiation barriers for GLP-1 agonist treatment, and promoting better adherence).

Ms. Walters informed us that come January 1, when a “surround sound” commercial strategy for Bydureon BCise goes into effect (a comprehensive approach to marketing/education through online channels as well HCP offices), the dual chamber pen will still be available, but AZ will no longer promote it. Clinicians will have to write prescriptions for Bydureon BCise, specifically, to get their patients the new autoinjector. She added that the company has “quite an extensive plan for patient support,” surrounding Bydureon BCise, which will likely include online videos to spread awareness and understanding on how to use the new device. It’s unclear at this time whether or not AZ will develop an app alongside. We note that Lilly does offer a patient-facing app to accompany its once-weekly GLP-1 agonist Trulicity (dulaglutide), and our sense is that this has contributed to the drug’s commercial traction (Trulicity revenue more than doubled YOY in 2Q17, reaching $480 million, while Bydureon revenue declined 6% YOY to $146 million). The IDEO-designed Trulicity pen has also received decidedly positive patient feedback, to our knowledge. Ms. Walters and Dr. McDermott explained that it’s hard to compare the new Bydureon autoinjector to the Trulicity pen without head-to-head data, but we imagine administering GLP-1 agonist therapy with Bydureon BCise will be much closer in nature to the IDEO-designed pen vs. the previous dual chamber pen or reconstitution trays.

  • According to Ms. Walters, the company anticipates pricing Bydureon BCise on par with the dual chamber pen. This would be incredibly good news for patients, and we imagine it would spur greater uptake of the autoinjector as well, boosting volume/sales for AZ’s GLP-1 agonist business. Bydureon sales fell 6% YOY in 2Q17 to $146 million, and accounted for 9% of pooled revenue from the GLP-1 agonist class (Novo Nordisk’s Victoza led this $1.6 billion market by value with 56% of pooled sales, while Lilly’s Trulicity was in second place with 30%). It remains to be seen how Bydureon BCise will be positioned on major formularies, and how payers will reimburse the product relative to the dual chamber pen – these factors will have significant influence on real-world use, though we’re hoping for strong payer coverage, given the compelling efficacy data and the potential for better adherence with this more patient-friendly device.
  • Dr. McDermott suggested that AZ may pursue a real-world evidence study on adherence with Bydureon BCise: “Adherence is a very important area, especially for GLP-1 receptor agonists, and we are looking into that space, especially with a once-weekly agent.” We’d be very keen to see this real-world analysis, and it would certainly fall in line with AZ’s goals in developing this patient-friendly product. The safety/efficacy of exenatide is well-known – Ms. Walters underscored that diabetes care providers have “incredible confidence” in that – but she put equal emphasis on ease of administration as a critical piece. As we’ve heard time and time again from thought leaders in the field, the best medicine on the planet won’t help diabetes if patients don’t take it. Following last week’s Advisory Committee meeting on Novo Nordisk’s semaglutide, Dr. Todd Hobbs, Chief Medical Officer for Novo Nordisk in North America, explained that a once-weekly regimen not only improves adherence, but also makes the initiation process smoother for injectable drugs like GLP-1 agonists. We’d expect adherence and initiation to be higher with a patient-friendly device like Bydureon BCise, and it could prove important in negotiations with payers to have real-world data backing this benefit.
  • Data from two head-to-head trials will be featured on the new product label: One comparing Bydureon BCise vs. Byetta (AZ’s twice-daily exenatide), and another comparing Bydureon BCise vs. Januvia (Merck’s DPP-4 inhibitor sitagliptin). The company announcement reports that overall, the exenatide autoinjector was associated with mean A1c reductions up to 1.4% and with mean weight loss up to 3 lbs after 28 weeks, whether taken as monotherapy or as an add-on to metformin, an SU, a TZD, or any combination of SU/TZD. While no concrete plans have been disclosed for future clinical trials of Bydureon BCise, Dr. McDermott speculated that it would be interesting to collect CGM readings and to investigate autoinjector exenatide administration in combination with AZ’s SGLT-2 inhibitor Farxiga (dapagliflozin). We’re strong proponents of more CGM use in clinical trials to elucidate the key benefits of advanced treatment options (particularly when it comes to glycemic outcomes beyond A1c), and we applaud AZ’s commitment to this (CGM data from the company’s DEPICT 1 study of Farxiga in type 1 diabetes showed the real prize of longer time-in-range).
  • The Bydureon autoinjector has also been accepted for active review by the EMA, on track with the expected 2H17. Assuming a standard 10-month regulatory review process, we expect an EMA decision in late 3Q18 or early 4Q18.
  • In our conversation with Ms. Walters and Dr. McDermott, we learned that the name “Bydureon BCise” is a play on “device” and “precise” – we love this!
  • Dr. McDermott also called attention to recent label updates for Bydureon and Farxiga, both of which now include results from DURATION-8 –  AZ is the first company to have positive data on GLP-1/SGLT-2 co-administration on its drug labels. Individually, these two therapy classes represent some of the most advanced diabetes medicines on the market, so you can bet we’re intrigued by the prospect of combination approaches with a GLP-1 agonist and an SGLT-2 inhibitor. One-year data from DURATION-8 was shared on a poster at ADA 2017, following the initial full results presentation (28 weeks) at EASD 2016 in Munich. A1c-lowering, weight loss, and reductions in systolic blood pressure were all significantly greater with Bydureon/Farxiga together vs. either agent alone. None of the effects were entirely additive, as is to be expected. We’ll be curious to see how AZ promotes Bydureon and Farxiga in light of the recent label updates, and we look forward to further commentary on this and the new autoinjector during the company’s 3Q17 earnings call (November 9). It’s great to note the company’s firm commitment to both its GLP-1 agonist business and its SGLT-2 inhibitor business, as we continue to believe these therapies should be in the hands of more people with diabetes, due to their profound glycemic efficacy and beyond-A1c benefits to body weight, blood pressure, postprandial control, time-in-range, and quality of life.


-- by Payal Marathe and Kelly Close