ADA: Invokana Obesity Data 'Astounds' Janssen

Johnson & Johnson subsidiary, Janssen Pharmaceuticals Inc., believes it has a game-changing obesity treatment in its portfolio – with potential in both diabetic and non-diabetic patients – in the form of marketed type 2 diabetes drug, Invokana (canagliflozin).

Janssen Pharmaceuticals Inc. presented positive Phase II proof-of-concept data for use of its sodium-glucose co-transporter 2 (SGLT-2) inhibitor Invokana co-administered with phentermine as a treatment for obesity at the American Diabetes Association conference, held in New Orleans June 11-14.

Invokana was approved in 2013 for the treatment of adults with type 2 diabetes but is not indicated for the treatment of chronic weight management.

Jim List, global therapeutic area head for cardiovascular and metabolism at Janssen, said in an interview on the sidelines of the ADA conference that the Phase II data for canagliflozin plus phentermine were "astounding" and possibly "the first in my career working in the metabolic field to show more than just an additive result."

The 26-week, randomized Phase II trial evaluated safety and efficacy of canagliflozin in combination with phentermine across four arms in 334 adults without diabetes and a body mass index of 30 to <50kg/m2 or, if with hypertension and/or dyslipidemia, a BMI of 27 to <50kg/m2 (mean weight, 102.9 kg; BMI, 37.3 kg/m2).

At 26 weeks, patients in the canagliflozin with phentermine arm experienced a significant placebo-subtracted reduction in systolic blood pressure (-4.2 mmHg; p=0.015) and demonstrated superior weight loss compared to placebo. The canagliflozin with phentermine, phentermine, canagliflozin and placebo arms produced weight decreases of 7.5%, 4.1%, 1.9% and 0.6% compared to baseline respectively (p<0.001).

Additionally, among the patients observed throughout the duration of the study, significantly more achieved ≥5% weight loss in the canagliflozin with phentermine arm versus placebo (66.7% versus 17.5%, p<0.001).

Janssen also noted the co-administration of canagliflozin and phentermine was well tolerated with no new or unexpected safety signals.

Invokana's Obesity Opportunity

"It's like finding the Holy Grail in endocrinology, and weight loss especially, to find two things that add up to more than the sum of their parts," List said. "This was exactly the case though in this trial, we saw some weight loss with each component alone but when we put the two together the combined weight loss was greater. Patients in the combined arm of the study lost around 7.5% of body weight from baseline at 26 weeks and their weight was still going down. This combination has great promise to be highly effective as a weight loss therapy."

Janssen is yet to confirm its next steps for canagliflozin in obesity, but List said all options were being considered, including the possibility of running a Phase III program specifically looking at this combination.

List also highlighted that the data come from a study that treated non-diabetic patients. "Traditionally patients with diabetes have more difficulty managing their weight, they are physiologically more resistant to weight loss," he said. "But canagliflozin allows you to excrete the glucose your kidneys filter and that filtered glucose is higher if your blood glucose is higher. Theoretically – and this still needs to be tested – this combination should work even better in diabetic patients and it already looks like it works pretty darn well in non-diabetic patients."

How It Works

The current obesity epidemic is driving a lot of other disease states – not just diabetes but also conditions like arthritis, cancer, sleep apnea and cardiovascular disease. A recent Centers for Disease Control and Prevention sponsored survey, published last week in the Journal of the American Medical Association (JAMA), found that 40% of women and 35% of men in the US are obese. "It’s a huge problem and we don’t yet have any highly effective medical therapies for it," List said, noting that while bariatric surgery is very effective, "it's not meant for everyone."

However, List said this obesity crisis is driving the search for alternative therapeutic treatments. "The very simple hypothesis we are working on is if we give patients something to block their appetite – in this case phentermine, a very widely used appetite suppressant for weight loss – would we be able to boost the amount of weight loss you get with canagliflozin?"

"The findings support the potential clinical impact that canagliflozin could have on the lives of people constantly having to manage their weight," List said.

[Editor's note: This article also appears in Scrip. The Pink Sheet DAILY brings selected complementary coverage from affiliated publications to our subscribers.]