"Even the Landlord's Pantry Is Tight": Eli Lilly Halts Two Phase II GLP-1 Trials Amid Strategic Pipeline Optimization

From past experiences, the reasons for terminating new drug development projects are varied, including mainly clinical trial results that failed to meet expectations, insufficient market competitiveness, a focus on advantageous projects, and a decline in drug demand due to changes in the external environment. The increasing cost pressure on pharmaceutical companies in new drug development has led to the suspension of several high-cost new drug developments.

In recent years, well-known multinational pharmaceutical companies such as Johnson & Johnson, Pfizer, and Biogen have all announced the termination of multiple new drug development projects, including some that had progressed to Phase 3 clinical trials. For example, on March 7, 2025, Johnson & Johnson announced the discontinuation of the Phase 3 clinical trial for its drug aticaprant, which was being developed to treat major depressive disorder (MDD), as the drug failed to demonstrate sufficient efficacy in clinical trials. On June 30, 2025, Pfizer announced the termination of an exploratory clinical study targeting patients with diffuse large B-cell lymphoma. The study originally planned to combine the SIRPα-IgG4 Fc fusion protein drug Maplirpacept with the chemotherapy drug lenalidomide.

Against this backdrop, multinational pharmaceutical companies are maintaining a cautious approach in their R&D pipelines. This is true even for "major players" like Eli Lilly and Company, which has a market value of nearly 700 billion USD and a revenue of 45 billion USD in 2024. According to Deloitte, the average cost of developing an innovative drug has now reached as high as 2.284 billion USD. One wrong move could affect the entire game.

As the "hottest star" GLP-1 faces extremely fierce market competition, companies like Novo Nordisk, Amgen, and Viking are accelerating the development of oral or long-acting GLP-1 products. Therefore, "the big player" Eli Lilly must adopt a "selecting the best from the good" strategy in product layout, terminating the above two experiments and allocating resources to the GLP-1 receptor agonist with positive Phase III clinical research data.Orforglipron, and to ensure its smooth commercialization, Eli Lilly is simultaneously building a complete supply chain and direct sales platform, including "LillyDirect"Online drug purchasing and multiple telemedicine platforms targeting different states, payers, and health conditions."

It is reported that another Phase II clinical trial of Naperiglipron is still ongoing. Eli Lilly and Company specifically mentioned this study in its latest Q2 financial report. The trial plans to recruit 275 obese or overweight patients, with an expected completion time of September 2026.

Eli Lilly and Company stated: "The research results will provide a reference for the next steps of this project."

In contrast, on August 26, Eli Lilly and Company announced that the third Phase III clinical trial (ATTAIN-2) of its oral small molecule GLP-1 receptor agonist orforglipron successfully met the primary endpoint and all key secondary endpoints, and the company plans to submit an application for market approval.

The study, named "Attain-2," primarily evaluated the efficacy of orforglipron in adult patients who are obese or overweight and have type 2 diabetes.

According to data disclosed on Eli Lilly's official website, at 72 weeks, patients achieved significant weight loss, a marked reduction in glycated hemoglobin (A1C) levels, along with improvements in cardiometabolic risk factors. Regarding the primary endpoint, based on efficacy estimates, patients taking 36 mg of orforglipron once daily (without dietary or caloric restrictions) experienced an average weight reduction of 10.5% (22.9 pounds), compared to only a 2.2% (5.1 pounds) decrease in the placebo group.

The market quickly reacted to this outcome. Analysts at Citi expressed optimism about this progress in their report, stating that orforglipron has the potential to become the first commercially successful oral GLP-1 due to its significant efficacy, high safety, good tolerability, and lack of dietary influence. HSBC analysts also upgraded Eli Lilly's previous "Sell" rating to "Hold," raising the target price from $675 to $700.

It is worth noting that the development of orforglipron once faced challenges.

On August 7, Eli Lilly and Company announced the data from its ATTAIN-1 Phase III study. This trial targeted non-Type 2 diabetes patients. According to the results disclosed on Eli Lilly's official website, at 72 weeks, participants receiving the highest dose treatment experienced an average weight loss of 27.3 pounds (12.4%).

Although the study met its clinical endpoint, the results did not fully meet Wall Street's high expectations. Previously, investors generally believed that orforglipron's weight loss effect would be comparable to Novo Nordisk's.Wegovy(Viego) is equivalent, with an average weight loss range expected to be between 13% and 15%, or even higher.

Meanwhile, concerns have been raised about drug side effects. According to official website data, the most common adverse reaction among participants receiving orforglipron (6 mg, 12 mg, and 36 mg) was nausea (at rates of 28.9%, 35.9%, and 33.7%, respectively), compared to only 10.4% in the placebo group.

More alarmingly, the discontinuation rate. Studies show that the discontinuation rate in the 36-milligram dose group was as high as 24.4%.

Affected by this, Eli Lilly's stock price plummeted 14% on the New York Stock Exchange that day, wiping out $100 billion in market value and marking the largest single-day drop in the past 25 years.

Now, with the positive data from ATTAIN-2, orforglipron has regained momentum.

In addition to the boost from efficacy data, its convenient medication method also makes Eli Lilly place special emphasis on it.

"The usage of this drug is very simple: just one pill per day, regardless of food or water intake. One pill not only helps patients lose approximately 27 pounds but also improves several key biomarkers, including blood pressure, blood lipids, inflammatory markers, and fasting blood glucose—precisely the aspects doctors focus on managing in preventive care," said Kenneth Custer, head of Eli Lilly's Cardiometabolic Health Division, during a teleconference.

Moreover, on September 3, 2025, Eli Lilly and Company registered the initiation of a Phase I clinical trial for LY4064912 for weight loss on Clinicaltrials.gov, demonstrating its continued investment and far-reaching layout in the field of obesity treatment.

In fact, GLP-1 class drugs have always been the core support of Eli Lilly's revenue. The most representative products include Mounjaro (Chinese trade name: 穆峰达; generic name: tirzepatide) for the treatment of type 2 diabetes (T2D), and Zepbound for obesity/overweight (weight management).

According to data compiled by the London Stock Exchange, in the second quarter of 2025, Mounjaro's sales reached $5.2 billion, significantly higher than the $4.74 billion previously expected by analysts; Zepbound's sales for the quarter reached $3.38 billion, also exceeding market expectations of $2.95 billion.

Eli Lilly's official website noted that, driven by the strong sales of both Zepbound and Mounjaro, the company's total revenue for the second quarter of 2025 surged 38% year-over-year to reach $15.56 billion. As a result, Eli Lilly raised the midpoint of its full-year revenue guidance by $1.5 billion, with the new range adjusted to $60 billion to $62 billion.

Against this backdrop, Eli Lilly's decision to abandon part of the clinical trials for Naperiglipron is closely related to the increasingly fierce market competition in the GLP-1 field.

The current market dynamics can be described as "a single move affects the whole situation." For instance, on the day Eli Lilly announced the data from its Attain-1 study, while its stock price plummeted significantly in New York, Novo Nordisk’s shares surged 6.7% in Copenhagen, marking the largest single-day gain in six and a half months.

For this reason, major pharmaceutical companies are racing to develop more efficient and convenient GLP-1 class drug candidates to capture market share.

For example, Amgen is advancingMariTideThe development. The drug aims to enhance GLP-1 receptor activity while inhibiting GIP receptor, designed as a once-a-month or even less frequent injection. In March this year, Amgen initiated two Phase III trials of MariTide for obesity treatment. "Maritime-1" is expected to recruit 3,500 participants who are obese or overweight but do not have T2D, with primary data anticipated to be released in early 2027; the other trial, "Maritime-2," targets 999 obese or overweight T2D patients, with results also expected to be released in early 2027.

Another company, Viking Therapeutics, announced in June 2025 the launch of its Phase III program "Vanquish" for VK2735, a GIP/GLP-1 receptor dual agonist. The drug is being developed in both oral and subcutaneous injection formulations for the treatment of obesity and other metabolic diseases. In August, Viking announced positive topline results from the Phase II clinical trial of the oral formulation of VK2735: participants experienced a significant average weight loss of up to 12.2% compared to baseline after 13 weeks.

At the same time, Novo Nordisk is also accelerating its layout. On May 2 this year, Novo Nordisk announced that the FDA has accepted the application for the weight loss indication of its oral version of semaglutide, marking an important step in the obesity drug market.

On August 31, Novo Nordisk announced new data that further reinforced the clinical value of Wegovy: compared with Eli Lilly's weight-loss drug, Wegovy can reduce the risk of heart attack, stroke, or death by 57%. Novo Nordisk emphasized that this cardiovascular protective effect is exclusive to the semaglutide molecule and cannot be generalized to other GLP-1 or GIP/GLP-1 treatments.

Notably, Caremark, a subsidiary of the U.S. pharmacy benefits management giant CVS Health, has reached an agreement with Novo Nordisk to grant Wegovy preferred access within its standard formulary, which covers tens of millions of people. This collaboration will undoubtedly diminish the market space for similar drugs such as Eli Lilly and Company's Zepbound.

Various external voices are "pressuring" Eli Lilly to focus its strategy more sharply, selecting the best from the best.

If approved, Eli Lilly's Orforglipron is expected to launch next year. Compared with the existing injectable Zepbound, Orforglipron not only has a simpler production process but may also be a more cost-effective option for patients. Therefore, Eli Lilly’s focus on allocating R&D and registration resources to Orforglipron, which holds the most promise and can be converted into cash flow at the earliest, is essentially a pragmatic response to probabilities of success and opportunity costs.

Notably, to truly drive the entire chain of oral GLP-1 drugs from clinical to commercial success, key links include: stable supply of raw materials and intermediates, formulation and specification gradients for the global market, negotiation pace with medical insurance payers, and synergy with the company's overall product line.

As early as January 2024, Eli Lilly and Company began breaking the limitations of the intermediary model by launching the "LillyDirect" direct sales platform, allowing patients to purchase medications directly online. The first product available on this platform was Eli Lilly's flagship drug, Zepbound. For a global pharmaceutical giant like Eli Lilly, transitioning from traditional production processes to a direct-to-consumer (DTC) distribution model marks a milestone operational leap.

Since patients still need prescriptions to purchase medications, Eli Lilly and Company is operating several different telemedicine platforms simultaneously during this process. Each platform targets different states, payers, and health conditions, providing differentiated配套 services.

In order to avoid repeating the shortage problems that occurred during the initial launch of Mounjaro and Zepbound due to overwhelming demand, Eli Lilly and Company is proactively establishing a supply system for Orforglipron in advance.

According to data disclosed by Eli Lilly, as of December 31, 2024, the company had accumulated pre-launch inventory worth $548.1 million, primarily related to Orforglipron.

Although stockpiling before a new drug launch is not uncommon, Eli Lilly's substantial investment clearly indicates special attention to orforglipron.

At the same time, for Eli Lilly and Company, "choosing the best from the best" does not mean "there is only one way."

According to information disclosed in its Q2 2025 earnings report, Eli Lilly and Company’s key focuses in regulatory, clinical, and business development also include: the new Alzheimer's drug Donanemab; the non-covalent (reversible) BTK inhibitor Jaypirca; the first clinical data from the next-generation FRα-targeted ADC program for platinum-resistant ovarian cancer; and the expansion of its pain medication pipeline through the acquisition of SiteOne Therapeutics.

This shows that Eli Lilly is trying to form a complementary cash flow pattern through multiple high-profile tracks, in order to disperse the impact of single-product fluctuations on the company's valuation and operations.

In addition, the cross-border integration of emerging technologies is also accelerating. For example, the combination of GLP-1 and CAR-T is opening up new imaginative space for the future.

On August 29, 2025, Peng Min's team from the Institute of Immunology at Tsinghua University published a paper in Nature Communications titled "GD2TIF cells as a platform for single-dose and long-term delivery of biologics," reporting a novel strategy that utilizes long-lived CAR-T cells as an in vivo drug delivery platform. In animal models, this technology achieved long-term stable release of GLP-1 drugs with a single infusion, maintaining long-term remission of obesity and diabetes. This breakthrough offers potential curative possibilities for chronic diseases requiring lifelong treatment.

Caught Between the "Cooling" of ATTAIN-1 and the "Warming" of ATTAIN-2, Eli Lilly Chose a More Challenging Path That Resembles a "Seasoned Industry Player" Rather Than Hedging Uncertainty with More Projects—Streamlining Narratives, Concentrating Resources, and Racing to Market. As the Entire Industry Evolves from Single-Product-Driven to a Multi-Track, Multi-Technology Integration Landscape, How to Achieve Breakthroughs Across Multiple Dimensions and Provide Broader Possibilities for Diversified Patient Treatment Options Remains to Be Seen by the Market...