For the stock prices of biotech companies, few events are as significant as the clinical trial results of their pipeline. In 2024, we've witnessed many biotech firms rapidly rise from the ground, and of course, there have been instances of crashes leading to closures. Based on secondary market performance, saying that a biotech's fate depends on the success or failure of a new drug does not seem exaggerated.

So, what about large multinational corporations (MNCs)?

Take Bayer, for example, which ranks among the top 10 globally by revenue. On November 20, 2023, its stock price dropped by 20%, retreating to 2009 levels, marking the largest drop in the company’s history, with a market value evaporating by about 7.6 billion euros. Before the sell-off, Bayer had halted its cardiovascular drug Asundexian in Phase III clinical trials due to its inability to outperform the control group.

Bayer's pain continued into 2024. In the first quarter of last year, the company laid off 1,500 employees, about two-thirds of whom were managers. Similarly, Pfizer, often referred to as a "global pharmaceutical giant," faced turmoil after its senior leadership cut two acquired products, sparking rumors of an internal crisis in 2024.

The financial reserves of these pharmaceutical giants do indeed allow them more room for trial and error, without worrying about the impact of each asset’s gain or loss. However, because "large ships are hard to turn," once a key clinical project fails, even the slightest fluctuations have far-reaching consequences.

Looking ahead to 2025, multinational pharmaceutical companies are also unlikely to have it easy, especially considering the looming patent cliff. At the annual JPM conference, companies like Johnson & Johnson signaled a strong push for mergers and acquisitions. However, the success of these transactions ultimately hinges on clinical outcomes. In 2025, whether in the high-profile weight loss drug sector, oncology, Alzheimer's disease, vaccines, or other fields, pharmaceutical giants are set to release important data, potentially causing stock prices to soar or plummet.

Eli Lilly

Few doubt that Eli Lilly will become the first pharmaceutical company to reach a market capitalization of one trillion dollars. The question now seems to be: when will it achieve this?

2024 has been a year of remarkable growth for Eli Lilly, with stock prices soaring by more than 60%, and its market capitalization crossing the 900-billion-dollar threshold at one point. If Eli Lilly’s new Alzheimer's drug provided the first boost, the diabetes and weight loss product portfolio is offering the second wave of momentum.

The global first and currently only approved GLP-1/GIP receptor agonist Tirzepatide, which is indicated for T2DM and long-term weight management, is Eli Lilly's expected trump card. In the first three quarters of 2024, the sales of Tirzepatide's weight loss version (Zepound) reached $3.018 billion, and the diabetes version (Mounjaro) earned $8.01 billion, totaling $11.028 billion in sales, accounting for about 34% of Eli Lilly’s total revenue during that period.

Eli Lilly is also considering other innovative opportunities. Since its $1.4 billion acquisition of a radioactive drug company in 2023, Eli Lilly has continued to show strong interest, particularly in target technology, to increase its chances of success.

However, in comparison, diabetes and weight loss treatments remain Eli Lilly’s primary revenue generators and the key to stock price fluctuations.

The GLP-1 agonist Orforglipron is expected to stand out in the next-generation competition. It is an oral version, whereas other approved weight loss drugs are all injectables. Analysts believe that an effective oral weight loss drug is easier to use and could become the ultimate winner.

According to Phase II clinical data for Orforglipron, patients taking the 45mg daily dose lost 14.7% of their weight within 36 weeks, while the placebo group lost only 2.3%. If this effect is amplified over time, Orforglipron will further consolidate Eli Lilly’s dominance.

The Phase III clinical trial for Orforglipron is expected to conclude in August 2025, with topline data to be released shortly thereafter.

Interestingly, the trial results of Orforglipron could also impact Roche, as Eli Lilly acquired the drug from Roche's subsidiary Chugai Pharmaceutical. Roche has another oral weight loss drug in early-stage trials.

Novo Nordisk

In comparison to Eli Lilly, Novo Nordisk, which is also deeply involved in the diabetes and weight loss market, had a rough year in 2024. The stock price increase in the first half of the year was offset by a decline in the second half, particularly after a clinical result was announced in December.

In December last year, Novo Nordisk revealed that its next-generation weight loss drug CagriSema had met the primary endpoint in Phase III trials, with subjects losing an average of 22.7% of their weight after 68 weeks of treatment, showing statistical significance and superior efficacy compared to the placebo. Despite this, Novo Nordisk’s stock price plummeted.

The investors' reaction largely stemmed from expectations. Earlier, CagriSema had successfully completed Phase II trials and entered Phase III development, with Novo Nordisk having set a target of at least 25% weight loss for the upgraded combination therapy.

The 25% target became a make-or-break number for competitors. In November 2024, Amgen disclosed Phase II results for its MariTide drug, which showed a maximum weight loss of 20%. Although this was higher than the 16% weight loss seen in Phase I, the company's stock price fell instead of rising.

In 2025, the results of CagriSema's second key Phase III trial (REDEFINE 2, targeting obese or overweight adults with T2DM) will be announced. Additionally, the company plans to conduct new Phase III trials to better determine the optimal dosage of the drug.

Besides the diabetes and weight loss market, CagriSema, like Novo Nordisk’s existing GLP-1 drugs such as semaglutide, has ambitious goals. For example, Wegovy has been approved for certain heart-related diseases. Novo Nordisk is conducting two clinical trials to explore the efficacy of Ozempic in patients with early Alzheimer's disease, with data expected in 2025.

Regarding the formulation battle with Eli Lilly, Novo Nordisk introduced an oral GLP-1 drug, Rybelsus, back in 2019, for the treatment of diabetes. Data released in November 2023 showed that the drug resulted in a 13.6% weight loss, while the placebo group lost only 2.2%, but it has yet to submit related marketing applications.

BioNTech

BioNTech, known for developing the COVID-19 vaccine, has also faced the pain of declining expectations.

In 2021, as the pandemic spread, BioNTech’s market value surpassed $100 billion, overtaking Gilead and double that of Bayer. However, today, this mRNA giant’s market value has fallen to less than $30 billion.

In the post-COVID-19 era, BioNTech has not given up. One way out is the development of various combined vaccines for infectious diseases, but considering the fading of the technology’s dividend, the uncertainty around commercialization has sharply increased. Another potential exit is the much larger oncology market.

It’s reported that the German pharmaceutical company has over 40 candidate drugs in development, four of which are in late-stage trials, with many showing positive results.

In July 2024, BioNTech announced that its mRNA vaccine BNT111, in a Phase II trial combined with a PD-1 inhibitor (Regeneron’s Libtayo), met its primary endpoint, significantly improving the overall response rate in patients with unresectable advanced melanoma.

As planned, in 2025, BioNTech will continue to report other mature data on the combination of BNT111 and Libtayo. Later in the same year or in 2026, BioNTech will disclose mid-stage data from the Phase II trial of Cevumeran (BNT122/RO7198457), co-developed with Genentech, for high-risk Phase II and III ctDNA-positive (circulating tumor DNA) CRC.

However, the launch of these products still requires a long wait. Meanwhile, as an old rival, Moderna, in collaboration with Merck, is developing mRNA-4157, which could potentially reach regulatory authorities as early as 2025.
Perhaps partly in response to this timing gap, BioNTech has already extended its focus to other fields, such as bispecific antibodies.
In November 2024, BioNTech acquired Prometheus Biosciences for nearly $1 billion, gaining full rights to its core pipeline asset, the PD-L1/VEGF bispecific antibody (BNT327). According to Phase Ib/IIa clinical results, this drug achieved an 18-month overall survival rate of 72.2% in combination therapies.
Thanks to favorable data from the PD-L1/VEGF bispecific antibody Ivonescimab compared to Keytruda, Summit, in collaboration with Akeso Biopharma, saw several consecutive days of significant stock price increases in September 2024. If BNT327 is launched as planned by the end of 2025, BioNTech is likely to enter a period of strong growth.

Pfizer

After crossing the $100 billion revenue mark in 2022, Pfizer has moved past its "lost two years."

With the decline of COVID-19 products, Pfizer's revenue shrank to $58.5 billion in 2023, a 41% drop compared to the previous year. In the first three quarters of 2024, increased demand for related products, along with collaboration from other sectors, led Pfizer to raise its 2024 revenue guidance. However, investors remain concerned about the future of this giant.

Compared to the peak stock prices during the COVID-19 period, Pfizer's performance in the secondary market today is disappointing. The stock price has dropped by about 50%, and its market value has evaporated by approximately $180 billion.

In October 2024, hedge fund Starboard Value turned its attention to Pfizer's CEO, Albert Bourla. After increasing its stake in Pfizer in previous months, the fund held $1 billion worth of shares and attempted to rally Pfizer's former executives for a "palace coup," demanding more effective restructuring and changes.

In some segments, such as vaccines, Pfizer still maintains a leading edge. In a sense, Pfizer is the only one among the "Big Four" vaccine makers continuing to progress aggressively thanks to its COVID-19 vaccine. The Prevnar series of products has long dominated the pneumococcal conjugate vaccine market, with $6.44 billion in revenue in 2023.

However, challenges are approaching. On one hand, Pfizer's old rivals are closing in.

In June 2024, Merck’s 21-valent pneumococcal conjugate vaccine, Capvaxive, was approved, marking the first product designed specifically for adults. Combined with the earlier market entry of Merck's 15-valent vaccine, Vaxneuvance, and the Phase I clinical trial for its pediatric vaccine V117, Merck is making a strong push.

Two other giants, Sanofi and GSK, are also making moves. By the end of 2024, Sanofi will launch a Phase III clinical trial for its 21-valent pneumococcal conjugate vaccine, expecting to submit for market approval in 2027.

Biotech companies should not be underestimated either. In September 2024, Vaxcyte released Phase I/II clinical data for its 31-valent pneumococcal vaccine, VAX-31. Its safety profile was comparable to Prevnar 20, and its immunogenicity was also impressive, resulting in a 45% surge in the company’s stock price, with a market value surpassing $13 billion. Vaxcyte revealed that the pivotal Phase III trial for VAX-31 will start in mid-2025.

Pfizer needs solid next-generation products to strengthen its position. The Prevnar 25 is currently undergoing Phase II trials, and a more advanced version is in the preclinical stage. Analysts expect that the Prevnar series will be updated in the second half of 2025.

At the JPM conference in 2025, Bourla expressed confidence in Pfizer's recently launched and under-development products, such as the CDK4 inhibitor Atirmociclib, which is in late-stage testing for breast cancer second-line treatment.

AbbVie

AbbVie seems to be an exception. If Novo Nordisk suffered from excessively high expectations leading to a gap, AbbVie, on the other hand, has remained relatively stable after being long underestimated and achieving modest but consistent results.

In 2023, before Merck’s Keytruda overtook it, discussions about whether Humira would lose its "drug king" title were ongoing. Humira, which has dominated the autoimmune disease market, surpassed Pfizer’s Lipitor in 2002 and held the "drug king" title for over a decade under patent protection.

In other words, over 20 years, Humira brought AbbVie more than $200 billion in sales. The market has been concerned about whether AbbVie can absorb the negative impact of losing this once-dominant revenue source.

Unexpectedly, the benefits from Humira are still being realized. In 2023, more than 90% of insured patients in the United States chose Humira instead of switching to cheaper generics.

According to AbbVie’s 2024 Q3 earnings report, the company generated $19.39 billion in revenue from autoimmune disease treatments, maintaining its position as the market leader. Humira's revenue decreased by 37.2% year-over-year, but it still generated $2.23 billion. New-generation products such as Skyrizi and Rinvoq are filling the gap with higher growth rates.

So, despite the ongoing decline in Humira sales, AbbVie’s future will increasingly rely on the development of its pipeline. AbbVie began planning the transition from old to new products years ago, and so far, things are looking good, but that doesn't guarantee smooth execution in the next step.

Rinvoq, used to treat non-segmental vitiligo, is in the late-stage trial phase, and results are expected to be announced in 2025. AbbVie’s Chief Medical Officer, Roopal Thakkar, noted that there is no systemic treatment approved for vitiligo yet, suggesting a huge growth opportunity for Rinvoq.

However, if the clinical data doesn't meet expectations, AbbVie may find it difficult to avoid a drop in its stock price.

Reference

Drug-Trial Results Could Shake Up Pharma Stocks in 2025. Watch Eli Lilly, Pfizer, and More.