Eli Lilly halts bima diabetes combination trial, Lantus "named" stock price surges

On September 25, according to the U.S. Clinical Trials Registry, Eli Lilly withdrew the Phase IIb clinical trial of ActRIIA/B monoclonal antibody bimagrumab in combination with the core component semaglutide tirzepatide for the treatment of patients with type 2 diabetes, citing "strategic business reasons."

The trial was originally planned to randomly assign 180 participants who were previously overweight or obese and had diabetes to receive bimagrumab, tirzepatide, or a combination of both, monitoring weight loss and fat/muscle distribution over 70 weeks. The trial was scheduled to start on October 21, 2024, and was expected to conclude in January 2027. Eli Lilly emphasized that routine evaluations of all projects were conducted to optimize resources, and did not disclose the specific reasons for the trial's termination. The outside interpretation is that the company needs to concentrate resources on advancing more promising obesity indication research.

This decision does not mean that Eli Lilly has abandoned the bimagrumab pathway. The company is still conducting a Phase II trial for non-diabetic obese adults, which also evaluates the combined effects of bimagrumab and tirzepatide. A company spokesperson stated that results will be read out in 2026.

In terms of timing, compared to the originally planned 2027 conclusion for the diabetes trial, the obesity indication reading is a year earlier, indicating that Eli Lilly is focusing its efforts on the more promising obesity field that is likely to receive approval first.

"High-Quality Weight Loss" Remains Important

Bimagrumab, developed by VersanisBio, can block Activin type II receptor (ActRII), thereby inhibiting muscle degradation and promoting muscle growth. In the BELIEVE Phase IIb trial, bimagrumab combined with the GLP-1 drug semaglutide resulted in an average weight loss of 22.1% over 72 weeks, with 92.8% of the weight loss coming from fat, while lean body mass remained almost unchanged; whereas semaglutide alone resulted in a weight loss of 15.7%, with only 71.8% coming from fat.

Even more surprisingly, bimagrumab alone not only resulted in a weight loss of 10.8%, but the weight loss was entirely from fat, and lean body mass actually increased by 2.5%. This result demonstrates that blocking ActRII signaling can address the muscle loss issue caused by GLP-1 drugs, achieving "fat loss without muscle loss."

However, "high-quality weight loss" is still in the early validation stage. The clinical community generally believes that future combination therapies must not only prove superior to GLP-1 monotherapy in weight control but also provide comprehensive benefits such as improved muscle function or optimized metabolic indicators.

Therefore, Eli Lilly's termination of the recruitment for the uninitiated diabetes trial is likely based on a comprehensive consideration of commercial priorities and resource allocation.

As of now, Eli Lilly's official website indicates that the Phase II trial for obesity indications is still in the recruitment phase. The trial targets adults aged 18–75, with an expected enrollment of 240 obese or overweight adults, comparing the safety and efficacy of different combinations of bimagrumab, tirzepatide, and placebo over 70 weeks. According to the timeline disclosed on the official website, the trial start and end dates are October 21, 2024 – January 2027, but the company has stated that the main results will be available by 2026 This means that if the efficacy is ideal, Eli Lilly could apply for the obesity indication for the combination therapy as early as around 2027.

In contrast, the trials for the diabetes indication have not yet officially started, the evaluation criteria are more complex, and the approval pathway is also more difficult; against the backdrop of the already mature effects of GLP-1 drugs in treating diabetes, it remains uncertain whether the addition of an antibody drug can demonstrate a significant advantage, which may be the fundamental reason for Eli Lilly's decision to cut this indication.

Opportunities for LianKai?

After the news of Eli Lilly halting the trial broke, LianKai Pharmaceuticals (02105.HK) saw its stock price surge against the trend. The stock price of LianKai Pharmaceuticals rose by over 15% at one point. This is partly because bimagrumab's withdrawal from the diabetes trial weakened potential competition, and also highlighted the value of the LAE102 pipeline in collaboration with Eli Lilly.

LAE102 is an ActRIIA monoclonal antibody independently developed by LianKai. In November 2024, the company reached a global collaboration with Eli Lilly, with Eli Lilly responsible for clinical development and commercialization in the U.S., while LianKai retains global rights. The company expects to announce preliminary results of the LAE102 multi-dose escalation study (MAD) in China and preliminary results of the U.S. Phase I trial in the "second half of 2025."

Previously, in June 2025, at the American Diabetes Association (ADA) academic conference, LianKai announced the first human study data:

• Design: Healthy subjects received a single intravenous or subcutaneous injection of LAE102, with a total of 4 dose levels; additionally, overweight and obese populations were recruited for exploration.
• Safety: No serious adverse events after a single dose, with most adverse events being grade 1 injection site reactions; no laboratory abnormalities.
• Pharmacokinetics/Pharmacodynamics: A single dose can lead to a short-term increase in ActivinA in the body, with this hormone elevated for about 28 days in the high-dose group, indicating a long half-life for LAE102 and its ability to sustainably inhibit the target; pharmacokinetic/pharmacodynamic data suggest potential efficacy of LAE102 in overweight and obese populations, supporting the advancement of subsequent clinical trials.

The obesity clinical research team at Zhongshan Hospital affiliated with Fudan University believes that this first-in-class antibody, LAE102, is expected to further reduce fat while maintaining lean body mass, providing a new tool for high-quality weight loss.

LianKai's management also emphasized that the company will collaborate with Eli Lilly to advance the combination therapy based on the efficacy of GLP-1 drugs, aiming to create the next generation of high-quality weight loss drugs with the concept of "fat reduction and muscle gain."

Market and Competitive Landscape

Following the wave of weight loss driven by GLP-1 drugs, more and more companies are targeting the "fat reduction without muscle loss" 2.0 era. The ActRII antibody developed in collaboration with Eli Lilly and Versanis is just one of them; Regeneron/ScholarRock's dual antibody combination, Veru's oral selective androgen receptor modulator enobosarm, and Biohaven's myostatin inhibitors have all successively announced early muscle protection data Most companies plan to combine muscle-modulating factors with GLP-1 drugs to demonstrate additional clinical benefits. Industry forecasts suggest that the market size for muscle-protective weight loss drugs is expected to reach tens of billions of dollars by 2035.

For Eli Lilly, although the diabetes indication for bimagrumab has been paused, the company's obesity pipeline remains strong:

• tirzepatide (Zepbound) has been approved for weight loss indications and is a star product in the market;
• retatrutide (GIP/GLP-1/glucagon triple agonist) is currently undergoing the Phase III TRIUMPH program;
• New-generation products such as orforglipron (oral small molecule GLP-1 agonist) are also being advanced;
• Collaboration with Camurus is developing a long-acting injection version, while the partnership with Juvena Therapeutics focuses on muscle health factors.

Eli Lilly's clinical adjustment of bimagrumab signals to the market that obesity indications have greater commercial priority, with related data readout times moved forward, further highlighting the potential of the new track for muscle gain and fat loss. Meanwhile, partners like LaiKai are also expected to benefit.

In the coming year, early results from the obesity trials of bimagrumab and tirzepatide will be announced, and multi-dose trials of LAE102 will also be launched. Will "fat loss without muscle loss" truly reach the public, or is it just a fleeting moment? Data will soon provide the answer