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EyesOn Strategic Agility
- Jana Chisholm
- Jun 22
- 7 min read
Strategic Agility in Action: How Biopharma Companies Are Managing Clinical, Commercial, and Operational Levers to Sustain Growth
Executive Highlights
Clinical success alone is not sufficient to ensure long-term growth. Biopharma companies must continuously adapt to changing scientific, commercial, and competitive realities to remain competitive.
Recent developments from Biogen, Denali, Eli Lilly, Regeneron, AbbVie, AstraZeneca, Johnson & Johnson, Astellas, Daiichi Sankyo, Gilead, and BioNTech demonstrate how organizations are actively adjusting strategic levers to maintain growth and competitive advantage.
Companies are becoming more willing to discontinue programs, redirect resources, expand indications, and reposition commercial portfolios when market conditions change.
The strongest performers are often not those with the largest pipelines, but those demonstrating the greatest agility in responding to new opportunities and emerging threats.
Strategy Does Not End at Launch
In previous PharmaTell analyses, we explored how successful biopharma companies increasingly manage multiple strategic levers simultaneously. Portfolio focus, capital allocation, business development, manufacturing footprint, market access, pricing, and clinical differentiation all influence long-term performance.
Strategy does not end once a product launches or an acquisition closes. The next challenge is execution. Clinical hypotheses can fail despite compelling biology. Competitors can reshape markets faster than expected. New indications can transform mature products into growth engines. Manufacturing networks built for one era can become liabilities in another. The companies that consistently outperform are often those that respond fastest when these realities emerge.
Clinical Portfolio Prioritization
Biogen and Denali Demonstrate the Importance of Knowing When to StopClinical Portfolio Prioritization
Few therapeutic areas have proven as difficult as neurodegenerative disease.
Despite decades of research and billions of dollars in investment, Parkinson's disease remains one of the industry's most challenging development areas. Disease-modifying therapies have repeatedly failed to demonstrate meaningful clinical benefit, even when supported by compelling biological rationale.
Biogen and Denali Therapeutics recently added another example to that list.
The companies announced that they would discontinue development of BIIB122 (DNL151) in idiopathic Parkinson's disease after a Phase 2b study failed to meet its primary endpoint. The decision marks the latest chapter in a collaboration that began in 2020 when Biogen paid Denali $400 million to jointly develop therapies targeting leucine-rich repeat kinase 2 (LRRK2), one of the most well-established genetic pathways associated with Parkinson's disease.
The scientific rationale appeared strong. Mutations in LRRK2 are linked to increased kinase activity, which researchers believe may contribute to protein aggregation and neuronal dysfunction. Approximately 4% of familial Parkinson's cases and 1% to 2% of sporadic cases are associated with LRRK2 mutations.
BIIB122 successfully achieved what many Parkinson's programs struggle to demonstrate:
More than 90% peripheral LRRK2 inhibition
Approximately 30% reduction in cerebrospinal fluid biomarkers
Drug exposure levels consistent with expectations
Evidence of meaningful target engagement
Yet none of these biological effects translated into improved clinical outcomes.
The 650-patient study failed to show that BIIB122 slowed disease progression compared with placebo. Secondary endpoints similarly failed to provide evidence of efficacy. This outcome reinforces that target engagement is not always the same as clinical benefit.
Importantly, Biogen and Denali did not abandon the entire LRRK2 hypothesis. Denali intends to continue evaluating the molecule in a genetically defined Parkinson's population where LRRK2 dysfunction may play a more direct role in disease biology. The company's ongoing Phase 2a study is evaluating approximately 50 patients with LRRK2-associated Parkinson's disease.
Analysts generally viewed this decision favorably. The failed trial demonstrated biological activity. What remains unclear is whether the mechanism can benefit a more precisely selected patient population.
The broader strategic lesson extends beyond Parkinson's disease. Historically, some pharmaceutical companies often continued investing heavily in programs long after warning signs emerged. Increasingly, current management teams are demonstrating a willingness to redirect capital toward opportunities with stronger probability-adjusted returns. Clinical discipline is becoming a strategic lever where success is no longer defined solely by advancing programs. It is increasingly defined by knowing when not to.
Commercial Execution as a Growth Driver
The Industry's Fastest Growing Companies Reveal a New Reality
The first quarter performance of the industry's largest companies provides a useful snapshot of how commercial strategy is evolving. Eight of the top twenty-five pharmaceutical companies reported double-digit year-over-year revenue growth during the quarter. What is particularly notable is that these growth stories are remarkably different. Some companies are benefiting from breakthrough products. Others are maximizing existing franchises. Several are successfully navigating patent cliffs.
Collectively, they demonstrate that commercial execution is becoming just as important as scientific innovation.
Eli Lilly: Aligning Multiple Levers Simultaneously
No company better illustrates this trend than Eli Lilly. Lilly reported revenue growth of 56% in the first quarter, the highest among major pharmaceutical companies and significantly above analyst expectations.
The company's growth was driven by tirzepatide, marketed as:
Mounjaro for Type 2 diabetes
Zepbound for obesity
Mounjaro generated $8.7 billion in quarterly sales, representing growth of 125%.
Zepbound contributed an additional $4.2 billion, growing 80% year over year.
While much of the industry discussion focuses on obesity itself, Lilly's performance reflects far more than product demand. The company has simultaneously executed across multiple strategic dimensions:
Manufacturing Expansion: Lilly has invested aggressively in production capacity to alleviate supply constraints that limited early adoption.
Market Access: The company continues expanding payer coverage and reimbursement pathways.
Indication Expansion: Tirzepatide's potential extends beyond diabetes and obesity into areas such as sleep apnea, cardiovascular disease, and metabolic dysfunction-associated steatohepatitis (MASH).
Physician Adoption: Continued investment in education and commercial execution has accelerated uptake across both endocrinology and primary care.
The result is a company that continues to raise guidance despite already extraordinary growth, increasing its revenue forecast to $82 billion to $85 billion. Another example of how effectively managing multiple strategic levers gives a company a competitive advantage.
Regeneron: Extending Growth Beyond a Mature Franchise
Regeneron provides a different but equally instructive example. The company reported 19% growth in the first quarter, its strongest performance since the COVID-19 era.
The primary driver was Dupixent. Developed with Sanofi, Dupixent generated $4.9 billion in quarterly sales, growing 33% year over year. Importantly, this growth was not driven solely by expansion within existing indications. but with the addition of recent approvals in:
Chronic obstructive pulmonary disease (COPD)
Chronic spontaneous urticaria
Bullous pemphigoid
At the same time, Eylea revenues declined 10%, falling below $1 billion for the first time since 2018.
Rather than allowing Eylea's erosion to define the narrative, Regeneron successfully positioned Dupixent as the next growth engine - lifecycle management executed effectively.
AbbVie: Recovering From the Humira Patent Cliff
Few companies have faced a larger commercial challenge than AbbVie. Humira was once the world's best-selling drug, generating more than $20 billion annually before biosimilar competition emerged. The loss of exclusivity created significant concern regarding AbbVie's long-term growth prospects.
The company's response now appears increasingly successful. Skyrizi and Rinvoq generated combined first-quarter sales of $6.6 billion, compared with $5.1 billion during the same period last year. Nearly all of AbbVie's revenue growth came from these two products. The timing of these two products is the key. Many companies spend years attempting to replace lost blockbuster revenue. AbbVie appears to have successfully transitioned from one immunology franchise to another, effectively managing strategic pipeline decisions and commercial execution to manage the generic erosion of Humira.
AstraZeneca, Johnson & Johnson, Astellas, and Daiichi Sankyo
Several other companies also provide valuable examples of strategic adaptation - leveraging strategic portfolio management to diversify revenues.
AstraZeneca reported 13% growth, supported by 20% growth in oncology and 19% growth in rare disease. Fifteen products generated at least $300 million during the quarter, highlighting the strength of the company's diversified portfolio.
Johnson & Johnson overcame a significant decline in Stelara revenues, which fell from approximately $1.6 billion to $656 million as biosimilar competition intensified. Tremfya grew 68% to $1.6 billion while Darzalex reached $4 billion, increasing 23%.
Astellas continued benefiting from newer growth drivers including Veozah, Padcev, and Izervay, gradually reducing dependence on Xtandi.
Daiichi Sankyo continues expanding its oncology leadership position through its antibody-drug conjugate portfolio. Management expects revenues to increase from approximately $13.2 billion in FY2025 to $19.1 billion by 2030.
Market Expansion and Lifecycle Management
Gilead Turns HIV Prevention Into a Growth Engine
Few recent launches illustrate the power of strategic execution better than Gilead's rollout of Yeztugo (lenacapavir). While much of the industry's attention has focused on obesity and oncology, Gilead has been building one of the most important commercial franchises in infectious disease. The launch of the company's long-acting HIV prevention therapy demonstrates the effective management of market development/expansion + commercial execution as well as providing a clinically differentiated product.
The Product Advantage
Yeztugo represents a fundamentally different approach to HIV prevention.
Unlike oral PrEP therapies requiring daily adherence or ViiV's Apretude, which is administered every two months, Yeztugo is dosed only twice per year.
One of the greatest challenges in HIV prevention has been adherence. Clinical studies demonstrated approximately 96% effectiveness in preventing HIV infection, placing Yeztugo among the most effective prevention options available. The simplicity of the dosing schedule meets patient needs and may ultimately prove to be the key driver in uptake and adherence the the community is looking for.
Commercial Expectations Continue to Rise
Gilead originally projected approximately $800 million in annual sales potential.
Analyst expectations have since increased to roughly $1 billion in first full-year revenue.
Yeztugo generated approximately $166 million in first-quarter sales, exceeding many launch expectations and suggesting stronger-than-anticipated uptake.
Expanding the Market Rather Than Fighting for Share
Rather than focusing solely on converting existing PrEP users, Gilead is actively targeting individuals who have never entered the prevention market. Despite years of education efforts, PrEP penetration remains relatively low in many high-risk populations.
Large portions of the United States remain underserved, particularly:
Rural communities
Southern states
Minority populations
Individuals with limited access to specialty care
Defending the HIV Franchise
Yeztugo is also serving a broader strategic purpose. For years, Gilead's HIV business has been anchored by Truvada, Descovy, and Biktarvy. The new long-acting therapies create an opportunity to transition patients to newer platforms before competitive pressures intensify.
The company is also advancing bictegravir/lenacapavir (bic/len), a once-weekly oral regimen that could eventually provide another differentiated option for HIV treatment.
Together, Yeztugo and bic/len represent the next phase of Gilead's HIV franchise.
Operational Realignment and Resource Allocation
BioNTech Repositions for an Oncology Future
Few companies have experienced a transformation as dramatic as BioNTech. At the height of the COVID-19 pandemic, the company became one of biotechnology's most visible success stories. Today, the company faces a very different challenge, reinventing itself to remain competititve.
A Pandemic-Era Infrastructure Meets Post-Pandemic Reality
BioNTech recently announced plans to eliminate up to 1,860 positions globally while restructuring several manufacturing and research sites. The restructuring is expected to generate approximately $585 million in annual savings by 2029. This is part of a strategic shift to reallocate capital, re-focus skills, and re-purpose technology on new markets.
Reallocating Resources Toward Oncology
BioNTech is redirecting resources toward:
Personalized cancer vaccines
mRNA oncology platforms
Cell therapies
Antibody-drug conjugates
Bispecific antibodies
The company is effectively shifting from a pandemic-era vaccine organization toward a diversified oncology company.
