GLP-1s have been the blockbuster biopharma story of the past few years, and these effective weight loss drugs will forever be the watershed moment in the long fight against obesity. Not to be religious, but from a calendar perspective, the pre-GLP-1 era might as well be like BCE. And yes, there are questions about maintaining the weight loss after people stop taking them, but the rapid weight loss and the attendant cardiac benefits are real.
However, if you think the story begins and ends with their effect on weight loss and their evolution from injectables to orals, think again. If the CEO of Eli Lilly and a Merck executive are to be believed, then this will be a class of medicines that can become a platform technology that can be applied to many types of diseases. In fact, the chief medical officer of Merck, who spoke on a BCG (Boston Consulting Group) panel on Tuesday during JPM Week, painted a picture of how this approach is evolving, largely driven by an accelerated pace of innovation.
“One of the things that’s different these days is that the innovation is transcending traditional therapeutic area names. So you have buckets of biology, inflammation, fibrosis, degenerative diseases, and they may have very, very similar pathways,” pointed out Eliav Barr, who is also Merck’s senior vice president and head of global clinical development. “So what’s interesting for us is medicines that enable a multifaceted approach. For example, you might have a medicine that is important in atherosclerotic cardiovascular disease or in joint disease or in something like Parkinson’s or HFpEF (a common type of heart failure), and it maybe all about inflammation. And so that actually is a very powerful way to take our discovery and our business development and consider how we can maximize the ability to impact foundational biologic mechanisms to help patients in a very broad population of spectrum of diseases.”
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And then Barr gave a clear example of that approach, which Eli Lilly, the Indianapolis drugmaker widely known for making the popular Zepbound GLP-1 drug, is adopting.
“Just as an example, look how Lilly had the combination of a classic rheumatologic drug or autoimmune disease drug, I should say, and their GLP-1 showing that you could improve not just weight, but also joint symptoms,” Barr explained. “So that TOGETHER study, I thought, was really clever and sort of the wave of the future where you might be able to address more than one disease in a given therapeutic cluster. So it’s not like, ‘Oh, I’m really interested in renal disease or not.’ It’s more [like], ‘I’m interested in inflammation. I’m interested in fibrosis,’ that kind of thing.”
Earlier this week, in an event hosted by Nvidia, which has made itself indispensable in the life sciences industry, David Ricks, CEO of Eli Lilly, expounded on the idea of moving GLP-1s beyond the immediate therapeutic areas of obesity and weight loss.
“We know you lose weight. We take our Zepbound today, you lose 23% of your body weight on average. But what we’re starting to uncover is a series of obvious things like reduced heart attack and other metabolic systems that improve diabetes, prediabetes. Conversion of diabetes drops by 93%,” Ricks declared.
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There are positives even beyond heart disease and prediabetes that are comorbidities of being overweight, and those are what Ricks classified as the “non-obvious” use cases for GLP-1s. The foremost among this group is the problem of inflammation.
“So being obese causes excess inflammation, not acutely like in response to an event, but chronically. And that’s not good for you. It’s not good for your cardiovascular system. It’s not good for your joints. And so spontaneously in our trials early on, people would report, ‘I just lost weight, but actually I can stand up from a sitting position for the first time in 10 years.’ Or some people with Crohn’s and colitis reported a kind of resolution of their symptoms.”
Referring to the TOGETHER-PsA open-label Phase 3b trial, which tests a Lilly psoriatic arthritis drug Taltz (ixekizumab) and Zepbound (tirzepatide) against Taltz alone, Ricks said that the combination boosted the efficacy of Taltz by 50%. Earlier this month, Lilly reported that in the study, 31.7% of patients in the Taltz plus Zepbound treatment arm achieved a 50% improvement in PsA activity, combined with weight reduction of at least 10%, compared to 0.8% of patients on Taltz monotherapy.
That’s an eye-popping result and more results will be published in the first half of the year.
Not all companies have GLP-1s in their arsenal, but the implication, broadly, for overall drug development in biopharma appears to be clear: A platform approach towards diseases as opposed to single therapies for single diseases may be the next evolution in drug development.
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