The Leading Source of Diabetes Business News It’s Complicated January/February 2011 • No. 105 The diabetes business used to be fairly straightforward. It’s a lot more complicated now, but that’s not a bad thing. Take insulin. After it was commercialized in the early 1920s, the goal was clear: sell more insulin. But look at today’s three major insulin makers: Eli Lilly, sanofi-aventis, and Novo Nordisk. For all three, to be sure, insulin is still preeminent. The diabetes divisions of Novo Nordisk and Lilly draw most of their revenue from human insulin and rapid-acting analogs, while sanofi-aventis’ blockbuster basal analog Lantus, as well as its mealtime insulins, continue to drive the bottom line. But all three companies have also developed (or are developing) GLP-1 analogs, Lilly has invested in oral drugs for type 2 diabetes (most recently through a major partnership with Boehringer Ingelheim), and the companies are also developing new therapeutic approaches for different stages of disease progression. The evolution of the insulin makers reflects broader industry trends. As our understanding of diabetes has expanded – and we dig deeper into the molecular complexities of the disease – it’s clear that single- focus large companies can no longer prosper. Ours is an era of individualized treatment that mixes and matches different drugs and technologies that try to meet the unique needs of every person with diabetes. Toward that end, companies are forming partnerships to find complementary therapies and development efforts that will create better, more streamlined options for patients. In this issue, for example, we report on Merck’s purchase of the glucose-dependent insulin company SmartCells; Roche’s acquisition of Marcadia and its dual GLP-1/GIP agonist; Abbott’s and Reata’s phase 2 results for their novel CKD treatment; XOMA’s and Servier’s collaboration for the anti- inflammatory drug candidate XOMA 052; Access Pharmaceuticals’ own oral insulin partnership with an undisclosed “major global pharmaceutical company”; sanofi-aventis’ collaboration with Harvard for translational research; GSK’s partnership to distribute Bioton’s human insulin in Russia; and AstraZeneca’s alliance with Evotec for beta cell regeneration. While these types of partnerships are hardly novel, the sheer number bodes well for more creative and ultimately effective therapies, including those for complications, for novel insulin formulations, and for earlier treatment of type 1 diabetes. Also in this issue, we speak to Dr. Sanjay Kaul, a noted cardiologist who’s on the FDA advisory panels for three weight-loss drug candidates – Qnexa, Lorqess, and Contrave. Dr. Kaul has given some of the strongest statements from anyone on the panel on the risk-benefit challenges for obesity medications. In our interview, he explains his wariness of REMS and post-approval efficacy studies, argues that clinical trial populations should reflect the comorbidities of the obese population at large, and voiced his view that a post-approval trial would be appropriate to assess Qnexa’s CV risk . We also summarize recent literature on obesity, which continues to generate significant academic interest even as the future for treatment therapies remains mixed. As we look ahead to another year, we hope that companies continue to collaborate, innovate, and persevere in their battle against these daunting public health challenges. Yours truly, Kelly L. Close Major Headlines Orexigen – Receives FDA complete response letter Requiring CV Outcomes Trial – page 8 Arena – Provides regulatory update; FDA requests more non-clinical studies – page 11 Amylin – FDA approves Bydureon tQT protocol; Byetta sales drop 17% – page 13 Vivus – May run retrospective study on topiramate teratogenicity – page 15 MannKind – Receives second complete response letter – page 17 Novartis – Gains new EU indication for Lucentis in diabetic macular edema – page 18 XOMA – Enters collaboration agreement with Servier for XOMA 052 – page 20 Valeritas – Receives 510(k) clearance for the V-Go; to launch in 2011 – page 32 Merck – Announces purchase of glucose-dependent insulin company SmartCells – page 34 Reata/Abbott – Release positive interim phase 2b results for CKD therapy – page 37 BMS/AZ – Receive FDA approval for Kombiglyze XR – page 40 Sanofi-aventis/Harvard – Collaborating for translational biomedical research – page 48 Diabetes Close Up #105 ~ January/February 2011 ~ It’s Complicated ~ www.closeconcerns.com 2 In This Issue 1. Quotable Quotes in Diabetes ..................................................................................................................... 6 2. diaTribe FingerSticks ................................................................................................................................ 7 3. DCU Company Watch ................................................................................................................................ 8 § Orexigen – Receives FDA complete response letter requiring CV outcomes trial for Contrave § Roche –Diabetes Care sales flat on year, down in 4Q10; taspoglutide and other drugs dropped § Pfizer – No mention of 11 diabetes compounds in pipeline in 4Q10 report § Eli Lilly – Humalog up 3.1% and Humulin up 5.5% in 4Q and 5% for year; teplizumab dropped § Novartis – Galvus franchise climbs; Lucentis approved for DME in the EU; pipeline shifts § AstraZeneca – Recognizes $32 million in Alliance Revenue for Onglyza § Arena – Provides regulatory update; FDA requests additional non-clinical studies § BMS – Onglyza ends 4Q10 with $73 million in sales; dapagliflozin MAA validated by EMA § Abbott– Diabetes Care up 1.5% for 4Q and 3% for full year; ~2-5% growth forecast for 2011 § Amylin – FDA approves Bydureon tQT protocol; Byetta sales drop 17%; Symlin sales grow 26% § J&J – Diabetes Care sales up 1.2% for 2010; US SMBG market share said to increase in Q4 § Amgen – Still no update on three diabetes compounds in development § Vivus – Reports on FDA meeting; may run retrospective study on topiramate teratogenicity § Diamyd Medical – Fully enrolls phase 3 US DiaPrevent; increased cash from OMJPI deal § FDA – Gives update on 510(k) changes, postpones decision on proposed class 2b § MannKind – Receives second complete response letter § Forest Laboratories – TTP399 glucokinase activator program to enter phase 2 trials in 1H11 § TransPharma – Renames transdermal drug delivery system ViaDor (formerly ViaDerm) § Novartis – Gains new EU indication for Lucentis in vision loss from diabetic macular edema § Lexicon – Announces positive clinical results for oral SGLT1/SGLT2 inhibitor LX4211 § ISIS – Adds obesity drug to metabolic pipeline; clarifies plans to launch chemistry 2.5 § XOMA – Enters collaboration with Servier for XOMA 052, announces phase 2a results § Zafgen – Announces topline results from phase 1b study for obesity drug candidate ZGN-433 § United Laboratories International Holding Limited (TUL) – China clears new insulins § GSK – Partners with Bioton to distribute human insulin in Russia § Novo Nordisk – Shares topline phase 3 data on Degludec/DegludecPlus; plans 2013 launches § Amylin/Eli Lilly – File sNDA for use of Byetta as an add-on to basal insulin § Takeda – Completes US patent litigation settlements for Actos and ACTOplus met § Abbott/FDA – Recall up to 359 million glucose test strips due to risk of falsely low results § Novo Nordisk – Partners for oral insulin licensing, Bangladeshi insulin manufacturing § Sanofi-aventis – Acquires worldwide rights to Ascendis' drug delivery platform for diabetes § Amylin – Starts filing metreleptin BLA in lipodystrophy-related diabetes, hypertriglyceridemia § Vivus – Applies for EU regulatory approval of Qnexa, replies to FDA complete response letter § Evotec/MedImmune/AstraZeneca – Partner for biologic beta cell regeneration program § Medtronic – Announces FDA approval and US launch of CareLink Pro 3.0 § WellDoc – Announces integration of DiabetesManager with electronic health records § Living Cell Technologies – Receives approval to market DIABECELL in Russia § Biodel – Plans to select a new Linjeta formulation to pursue by F1H11; pump data announced § Satiety – Launches TOGA procedure in the UK through the Nuffield Health Leeds Hospital § Orexigen – Discusses positive advisory committee vote for Contrave § Valeritas – Receives 510(k) clearance for the V-Go; to launch in 2011 § Access Pharmaceuticals – Partners with "major" company to test its oral insulin candidate § Allergan – FDA panel votes in favor of expanding LAP-BAND indication § Merck – Announces agreement to acquire SmartCells, develop glucose-dependent insulin § GSK – Drops development of SRT501 to focus on more potent SIRT1 activators § Sanofi-aventis – Announces plans to launch reusable insulin pen in India in 2Q11 § Novo Nordisk – Releases PK/PD data on coadministration of Victoza and Levemir § D. Medical – Revenue recognition hiccups; looking toward emerging market launch in 2011 § Medtronic – Worldwide Diabetes growth of 8.7% driven by solid international sales § Reata/Abbott – Release positive interim phase 2b results for bardoxolone methyl in CKD § Amylin/JDRF – Announce plans to investigate metreleptin as a treatment of type 1 diabetes Diabetes Close Up #105 ~ January/February 2011 ~ It’s Complicated ~ www.closeconcerns.com 3 § Bioton – Announces plans to partner with Actavis to market its insulin products § CVS Caremark – Plans rollout of pharmacist driven diabetes management initiative § Insulet – Revenue grows 36% and gross margins