The Slow March of Clinical Biomarkers to Become Surrogate Endpoints

Why It Matters

Accelerating biomarker acceptance could shorten development timelines and bring therapies to patients faster, while regulatory hesitancy risks delaying innovative treatments and increasing costs for payers.

Key Takeaways

• Clinicians seek biomarkers to replace hard clinical outcomes in trials
• FDA has approved only six biomarkers via its qualification program since 2007
• Regenxbio's RGX‑121 CRL highlighted FDA doubts on CSF HS D2S6 surrogate
• MRD negativity gained unanimous FDA advisory approval after extensive data accumulation
• BMS will outline biomarker selection framework at West Coast oncology conference

Pulse Analysis

The adoption of clinical biomarkers as surrogate endpoints has long been a tug‑of‑war between drug developers seeking faster pathways and regulators tasked with safeguarding patient outcomes. Since the FDA launched its Biomarker Qualification Programme in 2007, only six biomarkers have cleared the rigorous validation hurdle, reflecting a systematic preference for hard clinical endpoints. This conservatism stems from past experiences where premature surrogate reliance led to post‑approval setbacks, prompting agencies to demand robust, longitudinal data before granting regulatory credence.

Recent high‑profile cases illustrate the stakes. In early 2026, gene‑therapy pioneer Regenxbio received a complete response letter for its RGX‑121 candidate, with the FDA flagging the CSF HS D2S6 metric as insufficient to predict clinical benefit. Conversely, the oncology community celebrated the unanimous 12‑to‑zero endorsement of minimal residual disease (MRD) negativity for multiple myeloma, a decision that only materialized after years of pooled evidence. Such dichotomies highlight how disease prevalence, data depth, and unmet medical need shape the regulator’s calculus, especially in rare or neurodegenerative disorders where traditional survival endpoints are impractical.

Looking ahead, industry leaders are refining strategies to align scientific rigor with regulatory expectations. Ann Mongan of Bristol Myers Squibb will present a structured framework for biomarker selection at the Clinical Trials in Oncology West Coast conference, emphasizing question‑driven translational research over blanket surrogate adoption. Global harmonization efforts—spanning the FDA, EMA, and other agencies—suggest a gradual convergence toward evidence‑based surrogate acceptance, offering payers clearer value signals while preserving patient safety. Companies that can generate compelling, disease‑specific biomarker data are poised to accelerate approvals and capture market share in an increasingly data‑driven therapeutic landscape.