Read Part 1: Pharma's weight loss challenge: The incretin mimetic effect
As more incretin mimetics advanced through pipelines for type 2 diabetes, their weight loss properties began to shift from a nice perk to a lucrative opportunity.
“The drugs were proving very effective in managing non-insulin dependent diabetes. Then secondarily, as pharmaceutical companies often do, they looked for additional indications for the drugs, to quite simply, make more money,” points out Schabacker.
Profits (and judgment) aside, there is a verifiable health link between obesity and type 2 diabetes, which are often referred to as ‘twin epidemics.’ It’s estimated that 90% of type 2 diabetes patients are overweight or obese, and people battling obesity face the highest risk of developing diabetes. The risk of many of the common complications faced by patients with diabetes, such as kidney disease and cardiovascular issues, can be lessened by losing weight.
Long-time diabetes giant Novo Nordisk wasted no time getting out of the anti-obesity gate. By 2006, the Danish drugmaker was testing its GLP-1 agonist, liraglutide, in both type 2 diabetes and obesity.
In 2009, the drug ran into some safety delays on its road to approval in type 2 diabetes and Novo temporarily halted the phase 3 obesity studies while working with regulators to resolve concerns over pancreatitis and a rare type of thyroid cancer. The following year, Novo secured approval for liraglutide, branded Victoza, for type 2 diabetes and was able to confidently resume its trials in obesity.
Other drugmakers, including Amylin, GSK and Eli Lilly began grabbing up approvals of GLP-1 analogues in type 2 diabetes, and with each approval, conviction — and data — in the drug class was mounting.
In 2014, the FDA approved a higher dose version of Novo’s liraglutide, branded Saxenda, marking the first GLP-1 receptor agonist to get the green light as an obesity treatment — and the start of a pharmacologic shift in obesity care.
“For the first time, there was something with manageable side effects that seemed to be relatively safe even in the long term because diabetic patients had been using it for years,” notes Schabacker.
Celebrities weigh in
While Novo Nordisk’s Saxenda had the distinction of being the first anti-obesity incretin, it was the drugmaker’s next-gen GLP-1s that catapulted the drug class into weight loss stardom.
The FDA approved semaglutide, branded Ozempic, for diabetes in 2017 and a higher dose version to treat obesity, branded Wegovy, in 2021. The drugs’ effectiveness when it came to weight loss — in some cases up to a 20% reduction in body weight — along with some unsolicited celebrity endorsements on social media and even at the Oscars, sent prescriptions soaring.
The therapies have stolen the show financially too. When Novo Nordisk rolled out its recent second-quarter results, diabetes and obesity care sales had increased by 36%, driven predominately by the demand for GLP-1 therapies. Following the drugmaker’s early September launch of Wegovy in the UK, Novo usurped luxury brand company Moët Hennessy Louis Vuitton to become Europe’s most valuable firm.
Novo’s anti-obesity drug is also racking up accolades in the clinic. The results from two international trials reinforced Wegovy’s potential to enhance cardiovascular care. In the larger SELECT trial, the drug reduced the risk of major adverse cardiovascular events by 20% in adults with overweight or obesity.
Martin Holst Lange, the drugmaker’s executive vice president of Development, heralded the SELECT results as a major pharmacologic breakthrough, saying that Wegovy now “has the potential to change how obesity is regarded and treated.” Many doctors, including Ethan Lazarus, agree — but there is a catch.
“The treatment with pharmacotherapy is now becoming more compelling both because of the safety profile and potential benefits, but also the magnitude of the weight loss,” says Lazarus. “But right now, we have a significant problem in that we only have one highly effective drug approved for obesity, and Novo Nordisk can’t come anywhere close to meeting the demand for that drug.”
Wegovy first hit the FDA drug shortage list in March 2022 and currently remains there. It is joined by sister drug Ozempic — a supply issue that many attribute to off-label use of the drug for weight loss. One recent analysis found that 56% of patients newly prescribed Ozempic or Eli Lilly’s type 2 diabetes drug, Mounjaro, did not have diabetes.
For Novo Nordisk, manufacturing snags have further worsened the shortages. On two separate occasions, the FDA cited quality control issues at the CDMO plant that fills Wegovy syringes, later revealed by Reuters to be a Catalent facility. Novo has responded by ramping up production to 24/7, investing up to $4 billion a year to expand capacity and signing a second CDMO.
The incretin frenzy isn’t limited to Novo Nordisk drugs either. Between the drug’s impressive ability to reduce glucose levels in those with type 2 diabetes and off-label demand presumably inspired by weight loss, Eli Lilly has run into shortages with Mounjaro as well.
In May 2022, tirzepatide, branded Mounjaro, earned the distinction of becoming the first and only FDA-approved medicine that activates two different incretin receptors, GLP-1 and GIP, which the drugmaker says contributes to superior blood sugar control. The dual agonist also produced incredible results in a late-stage obesity trial, with patients losing as much as 22.5% of their weight.
With the treatment’s anti-obesity approval fast-tracked and in the hands of regulators, Eli Lilly has been ramping up supply efforts.
“We continue to invest and add manufacturing and supply capacity around the world,” says an Eli Lilly spokesperson. “With the addition of our manufacturing facility in North Carolina, coupled with additional actions and expansions at other sites, we are on track to achieve the goal we shared in November 2022 to double our incretin capacity by the end of this year.”
Despite extraordinary promise, for now, supplies of incretin drugs are limited — which means so is their impact on the obesity epidemic.
Continue reading Part 3: Pharma's weight loss challenge: Rewriting the script for obesity care
