The American Diabetes Association (ADA) 74th Scientific Sessions was held in San Francisco, CA from June 13-17, 2014.

Highlights of the conference included first Phase III data on LLY's new glargine, LY2963016 and SGLT-2/DPP-IV inhibitor fixed dose combinations (FDC) dapagliflozin/saxagliptin and empagliflozin/linagliptin. There was also important Phase III data helping to better gauge the profiles of several drugs. These included new and updated data on SNY's longer-acting glargine, Toujeo, and details on dulaglutide's trial versus Victoza, along with information about its injection pen. Finally, while there was no groundbreaking data on new mechanisms, there were important earlier stage results for LixiLan, the GLP-1 agonist/basal insulin combination, Transtech's oral GLP-1 program, a variety of faster- acting prandial insulins, and glucagon antagonist ISIS-GCGRRx.

The report covers a number of other drugs and topics, in addition. We also provide highlights from our post-ADA pulse surveys on SGLT-2 inhibitors and combos and GLP-1 agonists, as well as and comments from physicians at the conference.

Conference Highlights

Insulins

• First Phase III data from LY2963016 (LLY's new glargine [biosimilar]) showed similar profile to branded glargine (Lantus, SNY). Only small differences in immunogenicity, which an expert felt was not an impediment. Of course, patent litigation makes launch timing unclear.
• New and updated Phase III data for Toujeo (glargine U300, Ph III), SNY's more concentrated, longer lasting formulation of Lantus, showed similar efficacy as Lantus. Benefit on nocturnal hypoglycemia somewhat variable, though results trended in right direction. We provide detailed comparison with NVO's degludec, though in the US, Toujeo should have a first-to-market advantage.
• Weekly insulins are in development (data from Hanmi), but may only be suitable for certain segments of patients. XOMA is hoping that targeting allosteric binding site has advantages, but the preclinical data was quite preliminary.
• On faster acting prandial insulins, Biochaperone lispro (Adocia) may have a better PK profile than NN1218 (NVO) or BIOD-123 (BIOD). Largely negative feedback on prospects for inhaled insulin Afrezza, though after the conference, a license deal with Sanofi was announced.

SGLT Inhibitors

• First Phase III details from two SGLT-2/DPP-IV inhibitor fixed dose combinations (AZN's dapagliflozin/saxagliptin and Boehringer/LLY's empagliflozin/linagliptin) showed good reductions in A1c, though with less than additive effects from their components. As expected, weight loss was similar to the individual SGLT-2 inhibitor component.
• Remogliflozin (BHV, Kissei) presentations claimed a novel formulation could have a better profile than other SGLT-2 inhibitors by limiting overnight urinary glucose excretion, but the data were not clear.
• Physician attendees are largely still trying to understand how the class fits in treatment paradigm, though one convert noted they were more efficacious and infections were less problematic than expected.
  • KOLs had variety of views on weight loss versus GLP-1 agonists. A pulse survey also demonstrated a mix of views. A high proportion did feel weight loss is at least as good as GLP-1 agonists, but more so among primary care physicians (with the caveat that a number of respondents were likely early adopters).
  • Survey found SGLT-2/DPP-IV inhibitor combinations could become a popular component of SGLT-2 franchises.

GLP-1 Agonists

• Weekly dulaglutide (LLY) had a strong set of data, with AWARD-6 head-to-head trial against NVO's Victoza showing equivalence on most measures, except for slightly less weight loss. Details on convenient pen device were released.
  • A pulse survey projected a minority share, which was numerically lower than last year (15% share of class versus 25%), though within the variability of the surveys. ITCA-650 and exenatide suspension share projections close to those for dulaglutide.
• Early stage data on two oral, small molecule GLP-1 agonists, Transtech's TTP273 and TTP054, was presented. Some doses of TTP273 showed good mean glucose reductions, but variability in the data makes it difficult to assess how close the glycemic control may be to long- acting injectables. There are questions about how much weight loss they will show, but nausea is relatively low.
• First Phase IIb data from the LixiLan fixed dose combination (GLP-1 agonist/basal insulin) was somewhat disappointing, and more information is needed on subgroup analyses to understand what the company expects to see in Phase III. In contrast, updated one-year data from Xultophy's DUAL I showed continued, consistent benefit.
  • A pulse survey found that an FDC with a profile similar to Xultophy could be fairly popular.
• Details from Victoza's (NVO) trial in obese diabetics were incremental. Victoza had less weight loss than in prior trials of non-diabetic, obese patients, with a difference from placebo only slightly better than a study of oral Belviq (ARNA).

Glucagon Agonists

• Several companies are still working on the class, despite safety issues, with ISIS- GCGRRx (ISIS) showing quite strong glycemic control numbers. Dose-dependent increases in liver function tests are a concern, though the company has hypotheses it hopes to test on why these may not represent toxicity.

Other

• Investigators are waiting on Januvia's TECOS trial for a more definitive view on the risk of heart failure with DPP-IV inhibitors.
• There was news on other early stage compounds, including GPR40 agonist, DGAT1 inhibitor, liver selective glucokinase inhibitor, integrin antibody, mitochondrial uncoupler, and FGF21.

For the full report, please download the PDF version at the top of this page or contact your sales representative.

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