22nd European Congress on Obesity (ECO) 2015 Executive Highlights
Hello from picturesque Prague, where the 22nd European Congress on Obesity (ECO) has kicked off, complete with an opening ceremony featuring local Czech dancing and a saxophone quartet performance (so many international conferences take sharing of culture so seriously – we so appreciate this). The first packed day featured some notable commentary on obesity pharmacotherapy and bariatric surgery, along with a well-attended Novo Nordisk-sponsored symposium on emerging perspectives in weight management. Please see below for our top highlights of the day.
1. Drs. Dragan Micic (University of Belgrade, Belgrade, Serbia) and Roberto Vettor (University of Padua, Padua, Italy) expressed enthusiasm for specific combination therapies as the future of obesity pharmacotherapy. We think combination approaches are even more important than combination therapy – we would love to see manufacturers with serious resources buy organizations like Glooko on the digital health side or Omada and/or DPS Health on the chronic disease prevention side. Approaches would certainly be additive and perhaps even synergistic.
2. At a Novo Nordisk-sponsored symposium, Dr. Lotte Knudsen (Novo Nordisk, Copenhagen, Denmark) presented recently published data suggesting that the company’s obesity drug Saxenda (liraglutide 3.0 mg) induces weight loss by targeting central satiety and hunger signals. The satiety signal of course is very important and is obviously lending itself well to combination therapy on the diabetes side – we continue to hear a great deal of positivity on the GLP-1/SGLT-2 front.
3. Speakers highlighted GLP-1 agonists, SGLT-2 inhibitors, and metformin, among others, as promising drugs that can be used for weight loss.
4. ECO2015 Chair Dr. Martin Fried (Charles University, Prague, Czech Republic) stressed that with the new 2013 metabolic and bariatric surgery guidelines, the emphasis in the field on the bariatric surgery side has shifted away from weight loss in favor of the procedure’s metabolic effects.
5. In a separate press conference, Dr. Gary Zammit (Clinilabs, New York, NY) presented new data from the SCALE Sleep Apnea trial (n=359) demonstrating greater improvements in sleep apnea endpoints with Saxenda vs. placebo, likely due to greater weight loss.
Top Five Highlights
1. Drs. Dragan Micic (University of Belgrade, Belgrade, Serbia) and Roberto Vettor (University of Padua, Padua, Italy) expressed enthusiasm for specific combination therapies as the future of obesity pharmacotherapy. In a discussion of current obesity medications, Dr. Micic pointed to the therapeutic potential of “hybrid molecules,” specifically mentioning GIP, GLP-1, CCK, and glucagon as targets that affect beta-cell proliferation, insulin secretion, satiety, and energy expenditure. In particular, he cited results from a 2013 study demonstrating impressive metabolic benefits with GLP-1/GIP dual agonist in obese rodents – the same research team (led by Dr. Matthias Tschöp and Dr. Richard DiMarchi – the latter in particular who is very highly respected) recently published even more promising results with a GLP-1/GIP/glucagon receptor triagonist. In addition, Dr. Vettor highlighted the “scientific logic” of basal insulin/GLP-1 agonist combinations, which are finally beginning to reach patients with the recent launch of Novo Nordisk’s Xultophy (insulin degludec/liraglutide) in Switzerland. Dr. Micic also offered some thoughts on broader future trends in the worldwide obesity drug market. He predicted that in 2019, combination drugs will make up the majority of the market, followed by appetite suppression drugs, malabsorption drugs (which are forecasted to have a much smaller presence than they do today), and satiety drugs. Indeed, the obesity drug field has already been moving toward combination therapies: Arena and Eisai have reported positive safety results from a pilot study of lorcaserin/phentermine co-administration, and management has mentioned that a future fixed-dose combination is of interest. In addition, Orexigen continues to express interest in pursuing a fixed-dose combination of Contrave (naltrexone/bupropion) with a diabetes drug – we personally can’t wait to see this drug.
2. At a Novo Nordisk-sponsored symposium, Dr. Lotte Knudsen (Novo Nordisk, Copenhagen, Denmark) presented recently published data suggesting that the company’s obesity drug Saxenda (liraglutide 3.0 mg) induces weight loss by targeting central satiety and hunger signals. Explaining that Saxenda appears to have only a transient effect on gastric emptying (interesting), Dr. Knudsen presented a study exploring Saxenda’s effects on POMC/CART (satiety signals) and NPY/AgRP (hunger signals) neurons in the rat brain. Results demonstrated that rats that received peripheral injections of Saxenda indeed showed higher levels of POMC/CART mRNA and lower levels of AgRP/NPY mRNA compared to those on placebo. With advanced imaging technology, the researchers confirmed that Saxenda was targeting discrete regions in the rat brain, specifically in areas of the hypothalamus. Dr. Knudsen thus provided a proposed model of Saxenda’s actions, stating that the drug increases the frequency of action potentials in POMC/CART neurons, regulating appetite. While these are preclinical results, they provide important insights into other intriguing targets for future obesity therapies and could provide hints as to Novo Nordisk’s areas of focus in obesity research – check out our interview with Dr. Kevin Grove (head of the company’s new obesity research center in Seattle, WA) for more on this. In addition, this evidence of liraglutide’s access to the brain also provides support for the ongoing research on Novo Nordisk’s Victoza (liraglutide 1.8 mg) in Alzheimer’s disease – please see our coverage of this phase 2 study’s status for more details.
3. Speakers highlighted GLP-1 agonists, SGLT-2 inhibitors, and metformin, among others, as promising drugs that can be used for weight loss. Dr. Micic pointed to the demonstrated reductions in fat mass with SGLT-2 inhibitors and metformin’s effects on AMPK (a major metabolic regulatory enzyme) as evidence that these drugs can play important roles in weight management as well as glycemic control. Not surprisingly given the successful development of Saxenda, Drs. Micic and Vettor both also highlighted GLP-1 agonists as a particularly promising class; Dr. Vettor noted that exenatide once-weekly (AZ’s Bydureon) can also produce decent effects on body weight, though they do not appear to be as significant as those of liraglutide. Dr. Micic also noted that various other gut hormones (amylin, PYY, ghrelin, leptin) could potentially be targets for future pharmacological interventions. He mentioned pramlintide and metreleptin as examples of past efforts to address these targets, though he pointed out that Amylin and Takeda had to suspend clinical investigation of metreleptin after suggestions that neutralizing antibodies could block the effectiveness of the drug. Similarly, Dr. Micic mentioned melanocortin-4 receptor agonists as a promising class but noted that AZ had stopped development of its candidate due to the occurrence of a serious adverse event. Despite the past challenges, we agree that these targets may represent future important research areas as the search for additional obesity therapies expands.
- Dr. Micic emphasized the need to remove the distinction between treating obesity and type 2 diabetes, pointing out that we can “fight type 2 diabetes with anti-obesity drugs.” He stressed that for him, diabetes and obesity are “the same disease,” and he briefly presented data showing that orlistat, sibutramine, and rimonabant have all been able to show some improvement in glucose control. While these older drugs have largely fallen out of favor or been removed from the market or were never on the market in the US (rimonabant), we similarly see today’s branded obesity drugs beginning to move toward type 2 diabetes indications as Arena/Eisai, Vivus, and Orexigen/Takeda have all either reported favorable diabetes data or expressed interest in a diabetes indication for their obesity medications. Novo Nordisk, by contrast, has attempted to draw as clear a distinction as possible between Saxenda for obesity and Victoza for type 2 diabetes, though we imagine that this may be difficult to observe in clinical practice. In general, we agree that the lines between therapies for type 2 diabetes and obesity are becoming increasingly blurred moving forward and that the conditions will be conceptualized primarily as two manifestations of a broader underlying metabolic dysfunction.
4. ECO2015 Chair Dr. Martin Fried (Charles University, Prague, Czech Republic) stressed that with the new 2013 metabolic and bariatric surgery guidelines, the emphasis in the field has shifted away from weight loss effects in favor of the procedure’s metabolic effects. As Dr. Fried pointed out, this is reflected in the revised nomenclature in the European guidelines, which evolved from “surgery of severe obesity” to “metabolic and bariatric surgery.” Notably, he stated that both the European Association of the Study of Obesity (EASO) and Europe’s chapter of the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO-EC) now see type 2 diabetes as a reversible disease; the guidelines thus bring attention to surgery’s potential benefits in diabetes, provide definitions for remission, and discuss post-operative care of type 2 diabetes patients. Looking forward, Dr. Fried stressed that more research is needed to better understand how to assign which patients to which procedures and that physicians and surgeons must work together to provide the best patient care. Excitingly, he announced that EASO and IFSO-EC have taken this to heart and plan to host next year’s ECO together as a joint meeting. We are glad to see this collaboration at the organizational level as we agree that more effective team-based and multidisciplinary care will be critical as a broader array of obesity treatment options become available.
5. In a separate press conference, Dr. Gary Zammit (Clinilabs, New York, NY) presented new data from the SCALE Sleep Apnea trial (n=359) demonstrating greater improvements in sleep apnea endpoints with Saxenda vs. placebo, likely due to greater weight loss. In this double-blind trial, obese adults with obstructive sleep apnea (mean baseline Apnea-Hypopnea Index [AHI] of 49 events per hour; mean baseline BMI of 39 kg/m2) were randomized to either Saxenda or placebo as an adjunct to diet and exercise counseling for 32 weeks. At the end of 32 weeks, the Saxenda group experienced a substantially greater reduction in AHI than the placebo group (12 events per hour vs. six events per hour). Those on Saxenda also lost ~6% of their body weight vs. ~2% for those on placebo. Not surprisingly, the findings showed a significant association between AHI reduction and weight loss regardless of treatment; the safety profile also brought up no new signals or concerns. With these additional SCALE results, we are curious as to if Novo Nordisk would consider an OSA indication for Saxenda; Vivus recently announced in its 1Q15 update that it intends to seek such an indication for Qsymia (phentermine/topiramate). We hope it considers it if only to draw greater visibility to the problem.
-- by Melissa An, Emily Regier, and Kelly Close