Best-in-class vs first-in-class

From First-in-class to Finest: How Best-in-Class Drugs Reshape Pharmaceutical Leadership

Semaglutide, tirzepatide, pembrolizumab and Zanubrutinib illustrate how best-in-class drugs surpass pioneers, with China’s $51.9B licensing deals driving worldwide pharmaceutical growth.

SDW Editor

— 6 min read

History repeats itself in pharma. Ibrutinib opened the BTK inhibitor era, but zanubrutinib quickly became the market leader, as detailed in our recent SinoDrugWatch case study [23]. Lipitor overtook lovastatin. Semaglutide outshone liraglutide. Pembrolizumab surpassed nivolumab. Time and again, first-in-class (FIC) drugs break new ground — but best-in-class (BIC) successors capture long-term dominance. This review examines that cycle, providing fresh data from 2020–2025 and insights for China’s fast-rising pharmaceutical industry.

In pharma, first-in-class (FIC) drugs introduce a novel mechanism of action, addressing unmet medical needs and opening new therapeutic classes. Best-in-class (BIC) drugs follow by refining efficacy, safety, convenience, or dosing, often overtaking the FIC in market dominance.

The First-in-Class Edge—and Its Limits

FIC drugs target novel mechanisms, addressing unmet needs and commanding early dominance. Lovastatin (Mevacor, 1987) pioneered statins for cholesterol management, sparking a $125 billion market, while liraglutide (Victoza, 2009) introduced GLP-1 agonists for diabetes, peaking at $2.5 billion in 2015 [1,2,3]. However, limitations like dosing complexity or side effects invite competition [4]. A 2024 USC Schaeffer Center study found that BIC drugs outperform FIC drugs in market share in over 50% of drug classes within a decade, driven by clinical and market advantages [5].

Best-in-Class Takeover: Key Examples

BIC drugs refine their predecessors, improving efficacy, safety, or accessibility. Key examples from historical and recent 2024 sales data include:

  • Statins: Lovastatin reduced LDL cholesterol by 20–40%, but atorvastatin (Lipitor, 1996) achieved up to 60% reduction with better tolerability, peaking at $13.7 billion in 2006 [1,6]. The TNT trial and once-daily dosing cemented its dominance [7].
  • GLP-1 Agonists: Liraglutide was surpassed by semaglutide (Ozempic/Wegovy, 2017), with $17.45 billion (Ozempic, +25.8% YoY) and $8.44 billion (Wegovy, +85.7% YoY) in 2024. Semaglutide’s once-weekly dosing and 15–17% weight loss outshine liraglutide’s daily dosing and 5–10% weight loss [8,9]. Tirzepatide (Mounjaro/Zepbound, 2022), a dual GLP-1/GIP agonist, achieved $11.54 billion (+123.5% YoY) in 2024, with 20.2% weight loss in SURMOUNT-5, challenging semaglutide [8,10].
  • PD-1 Inhibitors: Nivolumab (Opdivo, 2014, FIC) trails pembrolizumab (Keytruda, 2014, BIC), with $9.30 billion (+3.3% YoY) versus $29.48 billion (+17.9% YoY) in 2024. Pembrolizumab’s 40+ indications and 20–40% better overall survival in NSCLC (KEYNOTE trials) drive its lead [8,11].
  • IL Inhibitors: Dupilumab (Dupixent, 2017, $14.15B, +22.1% YoY) outperforms adalimumab (Humira, 2002, $8.99B, -37.6% YoY) with biweekly dosing and efficacy in atopic dermatitis and asthma [8,12]. Risankizumab (Skyrizi, 2019, $11.72B, +50.9% YoY) surpasses ustekinumab (Stelara, $10.36B, -4.6% YoY) with quarterly dosing and 90% PASI 90 in psoriasis [8,13].
  • HIV Integrase Inhibitors: Biktarvy (2018, $13.42B, +13.3% YoY) outpaces FIC dolutegravir with a single-tablet regimen and high resistance barrier [8,14].
  • CD38 Inhibitors: Daratumumab (Darzalex, 2015, $11.67B, +19.8% YoY) improves PFS by 30–50% over FIC bortezomib in multiple myeloma [8,15].

Zanubrutinib (Brukinsa, 2019) exemplifies this trend, surpassing ibrutinib with 32–51% better PFS, 50–70% lower cardiac risks, and $1.74 billion in H1 2025 sales (+54.7% YoY), as detailed in our earlier post [16,17, 23].

From 2020 to 2025, 81 FIC drugs were approved globally (2023–2024), with 51.9% small molecules and 48.1% biologics, led by oncology (67%) and metabolic diseases (20%) [18]. China approved 113 innovative drugs (2019–2023), including FIC benvitimod (psoriasis) and BIC zanubrutinib [19].

A 2025 Health Affairs study notes faster US FIC approvals (81 vs. 63 in Canada, 1997–2020), but BIC drugs dominate due to clinical refinements [20]. Emerging BIC candidates include orforglipron (GLP-1, 12.4% weight loss) and linvoseltamab (bispecific, $2–3B projected by 2030) [21,22]. The GLP-1 market is projected to reach $157.5 billion by 2035 (CAGR 9.7%) [21].

In China, the NMPA approved 93 innovative drugs in 2024, a decade-high, including 48 class 1 drugs (23 small molecules, 22 biologics, 3 TCMs) [23]. FIC examples include Akeso's ivonescimab (global first PD-1xVEGF bispecific for NSCLC) and tunlametinib (first MEK inhibitor for melanoma), with 40 FIC approvals in 2023 [24].

BIC trends include 94 license-out deals in 2024 totaling $51.9 billion, a record, with antibodies leading (50%) [25]. The Priority Review Program accelerated approvals for urgent needs, boosting China's global share to second behind the US [26].

Why Best-in-Class Wins

BIC drugs succeed through:

  • Efficacy: Tirzepatide’s 20.2% weight loss vs. semaglutide’s 13.7%; pembrolizumab’s broader indications [8,10,11].
  • Safety/Convenience: Biktarvy’s single-tablet regimen; Skyrizi’s quarterly dosing [13,14].
  • Market Strategies: Keytruda’s 40+ approvals; China’s low-cost zanubrutinib (1/10th US price) [8,17].
  • Innovation: Dual agonists (tirzepatide) and novel mechanisms (linvoseltamab) [10,22].

Implications for China and Beyond

China’s pharmaceutical giants, like BeOne Medicines, InnoCare, and Zai Lab, are at the forefront of the BIC trend, leveraging regulatory reforms such as the Priority Review Program to accelerate approvals and foster “go-global” strategies [26]. Zanubrutinib’s success (75 markets, including China 2020) and orelabrutinib’s growth ($0.09B H1 2025) highlight China’s shift from generics to innovation, with 113 innovative drugs approved from 2019–2023 [17]. Zai Lab’s oncology and immunology portfolio — including PD-1 inhibitors and antibody-drug conjugates — illustrates how Chinese biotechs are simultaneously pursuing global markets [30]. License-out deals reached $51.9 billion in 2024 (94 transactions), doubling the market from 2023–2028 to $126.6 billion by 2030 [25,27]. Globally, this means more affordable BIC options, as seen with China’s biosimilars and partnerships (e.g., 23 semaglutide biosimilars by 2025) [28]. Challenges include tariff barriers and regulatory alignment, but China’s role in global supply chains and R&D (second-largest drug developer) promises accelerated BIC dominance, improving patient access worldwide [29].

Takeaway: Best-in-class wins because it refines: better efficacy, safer profiles, easier dosing, smarter pricing, and broader indications — these traits allow BIC therapies to surpass pioneers. For China, this trend is accelerating: with $51.9B in 2024 licensing deals and record NMPA approvals, its companies are becoming the world’s BIC engines.

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Disclaimer: For informational purposes only. Data are based on publicly available sources, company filings, and scientific literature as of August 31, 2025. Readers should consult healthcare professionals and relevant journals for medical decisions, and independent financial advisors for investment guidance.

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