Memorandum

Topline phase 3a SCALE-Obesity and Prediabetes results for Novo Nordisk’s liraglutide; 8% weight loss and 69% remission rate of prediabetes – May 23, 2013

Executive Highlights

  • Liraglutide 3.0 mg conferred a mean 8% weight loss from baseline, compared to placebo’s 2.6%.
  • Among people with prediabetes on liraglutide, 69% did not show signs of prediabetes at week 56 compared to 33% of people on placebo.

Novo Nordisk released topline results for its 56-week phase 3a SCALE-Obesity and Prediabetes study for liraglutide 3 mg in obesity earlier today. The trial enrolled 3,731 people who were obese or overweight with comorbidities such as prediabetes but not type 2 diabetes.

From a mean baseline weight of 106 kg (BMI of 36 kg/m2), participants on liraglutide achieved a mean 8% weight loss, compared to 2.6% for those on placebo – slightly better than the FDA's continuous benchmark for obesity drugs (a mean >5% placebo-adjusted weight loss). Categorically, 64% of people on liraglutide achieved at least 5% weight loss (vs. 27% for placebo) and 33% achieved weight loss of at least 10% (vs. 10% for placebo). As a reminder, the FDA's categorical requirement for obesity drugs is that the percentage of on-drug participants who achieve >5% weight loss must be at least 35% and twice the percentage of people on placebo achieving >5% weight loss.

It is difficult to compare across trials and we don’t like to do this unless there is head-to-head data. That said, and there may be a number of reasons for this, liraglutide's efficacy appears to be less than phentermine/topiramate ER's (Vivus' Qsymia; ~7-9% placebo-adjusted weight loss) and better than bupropion/naltrexone’s (Orexigen's Contrave; ~4-5% placebo-adjusted weight loss). In people without type 2 diabetes, liraglutide's efficacy might be superior to lorcaserin's (~3-4% placebo-adjusted weight loss), contrasting their more similar efficacy in people with type 2 diabetes (~3-4% placebo-adjusted). For details on liraglutide 3.0 mg’s mean weight loss in people with type 2 diabetes, please see our March 20, 2012 Closer Look at http://www.closeconcerns.com/knowledgebase/r/7c739985. KOLs, such as Dr. Luc Van Gaal (Antwerp University Hospital, Antwerp, Belgium) at Excellence in Diabetes 2013 have pressed that anti-obesity medications with mean weight loss of 10% are needed (for Dr. Van Gaal’s remarks, please see pg. 45 of our EiD 2013 report at http://www.closeconcerns.com/knowledgebase/r/3b6ae01c. Still, people respond to some drugs better than the mean. Thus, having more options on the market will increase the likelihood that a person has access to a drug they respond to and experience >10% weight loss.

Notably, liraglutide appears to improve and prevent prediabetes a finding we expect will increase uptake among payers. At week 56, 69% of the prediabetes subgroup (61% of all study participants had prediabetes) treated with liraglutide no longer showed signs of prediabetes, compared to 33% of the placebo-treated group. Among people without prediabetes at randomization, 7% of those on liraglutide and 21% of those on placebo developed prediabetes. We are curious what impact liraglutide use had on people transitioning from prediabetes to type 2 diabetes. People with prediabetes at baseline will receive liraglutide or placebo treatment for another two years, at which point analysis of this outcome might be more robust. In SEQUEL, Vivus' two-year trial of Qsymia (phentermine/topiramate ER), the drug reduced progression to type 2 diabetes by 54 to 76% compared to placebo.

Novo Nordisk expects to complete the remaining phase 3a trial, SCALE, in 3Q13 and to file the drug for obesity in the US and EU around the turn of the year.

  • Liraglutide 3 mg was generally well tolerated. The 56-week completion rate was 72% for liraglutide and 64% for placebo. Withdrawals due to adverse events were below 10% in both arms (specific withdrawal rates were not provided). The most common adverse events for liraglutide were GI-related (i.e., nausea) and diminished over time.

  • Compared to people on placebo, people on liraglutide 3 mg experienced statistically significant improvements in obesity-related risk factors, including blood pressure, cardiovascular risk biomarkers, lipids, and patient-reported quality of life At the European Congress on Obesity, Dr. Nicholas Finer (University College Hospital, London, UK) mentioned his belief that the next drugs to the European market will likely be gut peptide hormones (i.e., liraglutide). As evidence he cited the difficult regulatory environment centrally acting drugs (i.e., Belviq and Qsiva [the EU trade name for phentermine/topiramate ER]) have faced. For details on Dr. Finer’s remarks, please see pg. 18 of our ECO 2013 Day #2 report at http://www.closeconcerns.com/knowledgebase/r/f9de4ac7.

  • SCALE-Obesity and Prediabetes enrolled 3,731 people who were obese or overweight with comorbidities such as prediabetes, hypertension, and dyslipidemia but not type 2 diabetes. Participants were then randomized 2:1 to liraglutide 3.0 mg or placebo both in combination with diet and exercise.

-- by Hannah Deming and Kelly Close