Beyond the Scale: 6 Clinical Trials Tackling Obesity and Finding Suitable Therapies for Millions Worldwide

In the latter half of 2023 and throughout 2024, weight loss drugs have gained traction like never before. What was once a whispered name known only to a select few, Ozempic, developed by Novo Nordisk, now commands attention across social media platforms, even making its mark in Hollywood circles.

While the drug’s off-label use is doing the rounds on gossip blogs, fuelling the rumour mill by speculating which A-listers are turning to Ozempic to slim down, its rise signifies a broader phenomenon in the world of global health – a phenomenon that welcomes an entirely new era in obesity research.

See, obesity stands as one of the most pressing healthcare challenges in the world, affecting over 25% of Brits and a staggering 42% of Americans. While obesity is not necessarily a new health concern, our understanding of it has profoundly shifted. That’s since recent scientific advances have revealed obesity to be a complex interplay of environmental, behavioral and genetic factors, making its management equally intricate. As a result, researchers have come to understand that personalized treatment options are not only essential but a burgeoning priority that needs to be tackled.

Enter Life Sciences, armed with over 143 new molecules in clinical development and multiple global pharmaceutical companies crafting their own versions of GLP-1 and GIP receptors, which have demonstrated efficacy in weight loss by curbing appetite and regulating energy balance. So far, Novo Nordisk and Eli Lilly are leading the sector, both successfully pioneering GLP-1 and GIP drugs for weight loss and diabetes, with blockbuster drugs like Lilly’s Mounjaro and Zepbound and Novo’s Ozempic and Wegovy raking in billions of dollars in sales.

But as Novo and Lilly vie for dominance in the obesity therapy market, strategically expanding their portfolios through acquisitions, other pharmaceutical and biotech companies are joining the fray, amplifying the momentum with a flurry of new drug candidates aimed at broadening treatment options for patients worldwide. With the sector buzzing with all of this activity, obesity and metabolic drugs are poised to become a defining trend throughout the coming years, with market projections soaring to between $100 billion and $200 billion by 2030.

In light of these very developments, we’re delving deep into this competitive landscape, gaining a better understanding of the intricacies of obesity by exploring six clinical trials that are pushing the Life Sciences industry forward in finding reliable and suitable therapies for millions worldwide.

1.    BioAge to Test Their Phase II Drug, Azelaprag, Alongside Eli Lilly’s Zepbound to Help Patients Lose Weight While Preserving Muscle Mass

Originally founded a decade ago to combat age-related conditions, BioAge Labs has pivoted its trajectory to concentrate on addressing the pressing issue of obesity—an evolution symbolic of its commitment to pioneering transformative therapies that resonate with evolving healthcare needs.

In a significant stride forward, the biotech startup secured a substantial $170 million in funding in February to bolster its experimental pill, azelaprag’s development, set to be tested alongside established weight loss medications like Wegovy and Zepbound.

This Series D financing round saw participation from the venture arms of industry heavyweights such as Amgen and Eli Lilly, both deeply invested in the realm of obesity therapeutics. The anticipation surrounding BioAge’s endeavors stems from the uniqueness of its drug, engineered to replicate the behavior of a biological molecule typically activated through exercise – a feature potentially pivotal in preserving muscle mass.

Initially, the drug was conceived to address muscle preservation in the elderly; however, its newfound application in aiding rapid weight loss among obese individuals has sparked considerable interest. This comes from BioAge’s Phase I study, which yielded promising results, demonstrating that participants administered azelaprag during bed rest experienced significantly less thigh muscle mass loss compared to those receiving a placebo. 

With these encouraging findings, BioAge finds itself thrust into the heart of one of the pharmaceutical industry’s most lucrative pursuits – the obesity market, which has attracted a myriad of both established and emerging players, all striving to enhance existing treatment modalities.

Addressing a prevalent concern surrounding incretin medications potentially inducing lean body mass loss during rapid weight reduction, BioAge asserts that its preclinical data suggests combining its drug with incretins could amplify weight loss while concurrently improving body composition and muscle function. Central to its mechanism of action is the stimulation of apelin, a peptide associated with muscle function that tends to diminish with age.

Looking forward, BioAge’s upcoming Phase II study aims to validate this hypothesis in humans. Scheduled to commence later this year, the trial will evaluate azelaprag alongside Zepbound in individuals grappling with obesity, with Eli Lilly lending support by providing Zepbound as part of their collaborative effort.

2.    Boehringer’s Drug Servodutide Progresses into Phase III Trials After Demonstrating 19% Weight Loss 

In an effort to challenge Novo Nordisk and Eli Lilly’s dominance of marketed GLP-1 therapies, German pharmaceutical giant Boehringer Ingelheim, in collaboration with Zealand Pharma, is propelling forward with its obesity drug developments. This partnership, with roots dating back to 2011, emphasizes their commitment to pioneering effective solutions for combating obesity.

Moving forward with that mission, last summer, Boehringer unveiled compelling mid-stage trial data for their drug survodutide, revealing that overweight or obese participants achieved nearly one-fifth reduction in body weight following one year of treatment.

The randomized, parallel-group Phase II trial lasted 46 weeks and used a once-weekly dosing regimen. During 20 weeks, participants received a dose escalation, followed by 26 weeks of maintenance across varying dosage levels (0.6mg, 2.4mg, 3.6mg, and 4.8mg).

Results found that participants receiving a 4.8mg dose of survodutide achieved an average weight loss of nearly 19%, with an impressive 40% attaining a weight reduction of at least 20%, contrasting starkly with the placebo group’s outcomes. Moreover, findings indicated that weight loss trends with survodutide had not reached a plateau by week 46, suggesting the potential for further efficacy with prolonged treatment durations.

While survodutide demonstrated an acceptable safety profile overall, gastrointestinal side effects, consistent with other therapies in the field, were noted among some participants. Importantly, most adverse effects leading to premature trial discontinuation occurred during the rapid dose escalation phase, prompting considerations for a more gradual dose escalation regimen to mitigate such occurrences.

But the key takeaway from Boehringer’s survodutide is that it distinguishes itself from existing therapies by not only targeting the GLP-1 protein receptor but also the glucagon receptor – a dual-pronged approach aimed at modulating appetite and enhancing energy expenditure, particularly through liver mechanisms. This innovative strategy represents a shift in obesity therapy, departing from conventional interventions solely focused on curbing energy intake.

What’s more, beyond the drug’s potential in obesity management, survodutide is also being investigated for its efficacy in treating non-alcoholic steatohepatitis and liver fibrosis, underscoring its multifaceted therapeutic potential.

3.    Novo Nordisk’s New Drug Amycretin Saw 13% Reduction in Body Weight in Small Clinical Trial

Just earlier this month (March 2024), groundbreaking clinical trial findings emerged, revealing the potential of Novo Nordisk’s newest experimental drug, amycretin, to combat obesity. 

In a Phase I trial involving 144 participants, amycretin demonstrated remarkable efficacy, with those receiving the drug experiencing a staggering 13% reduction in body weight over a three-month period. In contrast, those administered a placebo witnessed only a marginal 1% decrease in body weight during the same timeframe.

An important factor of these new developments is that amycretin, distinct from Novo’s widely successful injectable, Wegovy, is administered orally and targets two gut hormones, GLP-1 and amylin, which are both known to influence appetite and blood sugar levels.

While the findings from this early trial are categorized as ‘exploratory’ due to not meeting statistical significance criteria, they still sent shockwaves throughout the Life Sciences sector as the race for the next best obesity drug intensifies.

It’s also worth noting that neither Novo’s Wegovy nor Eli Lilly’s Zepbound achieved more than a 10% reduction in weight after 12 weeks in their respective studies for approval. Thus, amycretin’s reported outcomes represent a significant leap forward, positioning it at the forefront of weight loss efficacy in obesity drug testing.

So, as beady-eyed analysts and investors weigh up each new contender within this competitive landscape, Novo went ahead and presented the latest trial data to investors earlier this month, marking the finding as a significant development in the pursuit of effective obesity treatments. The ripple effect of this early breakthrough data is already apparent, with Novo’s stock surging by an additional 8%, signalling investors’ confidence in amycretin’s potential impact.

4.    Viking Therapeutics’ Injectable Resulted 15% Weight Loss in 13 Weeks

Last year, Viking Therapeutics unveiled promising results from their Phase I trial of VK2735, with participants receiving the highest dose of the drug experiencing a substantial 7.8% reduction in body weight over four weeks.

Fast-forward to February 2024, Viking revealed findings from their Phase II study, which involved 176 obese or overweight patients with at least one weight-related health condition. Randomized into groups, participants received varying doses of VK2735 or a placebo over a span of 13 weeks.

Noteworthy outcomes emerged from the trial, indicating substantial weight loss across VK2735 dosage groups. Those administered the lowest dose of 2.5mg a week witnessed an average weight reduction of 9.1%, surpassing placebo recipients by 7.4%. Encouragingly, weight loss effects intensified with escalating doses, with individuals receiving the highest dose of 15mg a week achieving an impressive 15% reduction in body weight.

Of particular significance is the remarkable number of participants achieving a 10% or more reduction in body weight, notably higher among those receiving the highest VK27325 dose, with approximately 88% reaching this threshold – a testament to the drug’s efficacy.

Yet despite these promising results, the trial did reveal some notable side effects, particularly at higher dosage levels. While consistent with common side effects observed in similar drugs, nausea was reported by 63% of participants receiving 15mg weekly, with 29% experiencing vomiting. 

Still, expectations were surpassed, with initial forecasts projecting an 8% reduction in body weight. This has meant that since the release of the Phase II trial data, Viking’s market value has surged by over $3 billion, underscoring the significance of these findings and the potential of VK2735 to emerge as a formidable competitor to existing obesity treatments. 

5.    Eli Lilly’s Orforglipron Shows Weight Reduction of Up to 14.7% in 36 Weeks 

Expanding upon its already strong obesity therapy portfolio, Eli Lilly recently unveiled Phase II data for its groundbreaking nonpeptide oral GLP-1 receptor agonist for chronic weight management and type 2 diabetes.

The meticulously designed study lasted 36 weeks and assessed the safety and efficacy of orforglipron across various dosage levels (12mg, 24mg, 36mg, or 45mg) compared to placebo among obese or overweight individuals with at least one weight-related comorbidity (excluding type 2 diabetes).

The drug was administered every morning as an oral capsule and was evaluated in conjunction with ongoing healthy eating and exercise education provided by study personnel throughout the trial. The findings, publicized in the New England Journal of Medicine, showcased orforglipron’s remarkable efficacy in driving significant weight reductions among obese or overweight adults with weight-related comorbidities.

Among the participants with a mean baseline body weight of 240lbs, those allocated the placebo or varying doses of orforglipron exhibited distinct trajectories over the study duration. At the 26-week mark, orforglipron demonstrated statistically significant, dose-dependent reductions in body weight, ranging from 8.6% to 12.6%. In contrast, a minimal 2% reduction was observed in the placebo group.

As the trial progressed to the 36-week juncture, the weight-reducing effects of orforglipron persisted, with all dosage levels showcasing notable body weight reductions ranging from 9.4% to an impressive 14.7% – a stark contrast to the modest 2.3% reduction witnessed in the placebo cohort.

This compelling data underscores orforglipron’s potential to revolutionize chronic weight management, offering a promising avenue for individuals battling obesity and its associated health complications.

6.    Roche has Rearranged its Early-Stage Pipeline to Get Onboard with the Obesity Drug Rush 

Following their acquisition of startup biotech Carmot Therapeutics at the end of last year, Roche is strategically realigning its early-stage drug pipeline, dropping three oncology candidates and five neurological compounds, including two aimed at Alzheimer’s disease. This strategic maneuver seeks to create space for a suite of obesity treatments, aligning with Roche’s objective to “increase their overall portfolio value and speed up development.”

Central to Roche’s pivot are three drugs obtained through the Carmot transaction, all targeting a metabolic pathway that stimulates insulin production known as GLP-1. As we know, sales within this drug class have recently skyrocketed, propelled by their potent weight-loss effects. 

Among Carmot’s assets, two drugs in Phase II trials are injectables acting on a secondary insulin-boosting metabolic pathway called GIP, the same active ingredient in Eli Lilly’s diabetes and obesity medications, Mounjaro and Zepbound. One of these injectables, administered hypodermically once weekly, is currently advancing through development.

Additionally, a third Carmot compound exclusively targets GLP-1 and is administered orally, representing another avenue in Roche’s obesity therapy pursuit as they join the race to find the most effective treatment. 

Conclusion

Obesity therapies in Life Sciences are indeed witnessing remarkable advancements fueled by innovative research and strategic collaborations. From novel drug developments to dual-targeting approaches, pharmaceutical efforts are dedicated to delivering effective solutions for weight management and metabolic health improvement.

Recent strides, exemplified by the breakthroughs mentioned above, highlight the industry’s commitment to addressing the complex challenges of obesity. As we’ll witness, 2024 is set to create meaningful change, promising newfound hope for obesity patients worldwide.

Want to know what other trends in Life Sciences are expected to surge throughout 2024? Explore more in From AI to CRISPR: 5 Trends Shaping the Life Sciences Industry in 2024. 

And remember, whether you’re looking to elevate your team or advance your career in Life Sciences, we’ve got the tools to help! Contact us today to find out how we can support you.