Strategic Forecasting in Pharma Beyond the Clinical Lens
Posted by | Ankita Dutta, Ph.D.
Despite unprecedented innovation, nearly half of all new drug launches fail to meet analysts’ expectations.
Industry data consistently shows that 40–50% of therapies underdeliver commercially, revealing a persistent disconnect between clinical promise and real-world performance.1–3
This persistent disconnect between clinical promise and commercial performance highlights a key limitation in how forecasting is generally approached — with an over-reliance on clinical outcomes and addressable patient numbers, while overlooking market complexity, operational readiness, and payer dynamics.
When Breakthrough Science Meets Commercial Reality
A vivid example of this disconnect is observed in the case of Zynteglo, a one-time gene therapy developed by Bluebird Bio for transfusion-dependent beta-thalassemia (TDT), a rare genetic disorder requiring lifelong blood transfusions.4
Despite Zynteglo’s promising clinical profile and initial commercial enthusiasm, its market performance starkly underdelivered — underscoring the complexities of forecasting in the emerging cell and gene therapy (CGT) space.
In Phase 3 clinical trials, over 80% of patients treated with Zynteglo were transfusion-independent for at least a year, with most achieving near-normal hemoglobin levels.5,6
Promising clinical data for a compelling unmet need and strong regulatory endorsements from both the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) positioned Zynteglo as a potential blockbuster.
The product’s clinical benefit and value-for-money were further bolstered by a 12-member independent appraisal committee.7
At a list price of $2.8 million per dose, analysts confidently forecasted sales exceeding $1 billion by 2024.8
However, between 2021–2024, Zynteglo generated only ~$80 million in total revenue — about 10% of initial forecasts (Until Q4 2024, Fuld analysis, 2025).
Why Zynteglo Fell Short
Zynteglo’s commercial shortfall wasn’t due to a lack of clinical success — it was a result of systemic market adoption barriers:
- Payer Barriers: Failed reimbursement negotiations in the EU, largely due to pricing concerns, resulting in market withdrawal.
- Operational Barriers: Manufacturing delays and limited treatment site readiness slowed U.S. adoption with fewer than 20 active treatment centers.
- Patient Barriers: Lack of reimbursement for ancillary services such as fertility preservation further deterred eligible patients from pursuing treatment.
Zynteglo’s story underscores a vital truth: even transformative therapies can stumble when forecasting models fail to capture the real-world environment.
Forecasting from a Broader Lens
To better reflect real-world adoption barriers, forecasting models must incorporate a broader range of variables, including:
- Payer expectations and evolving value-based access models
- Manufacturing scalability and standards in centralized or decentralized settings
- Treatment infrastructure readiness and provider capacity constraints
- Real-world patient, provider, and caregiver perspectives
- Regulatory and policy developments across different markets
- Competitor actions and strategic market entries
Without factoring in these interdependencies, even the most promising therapies risk underdelivering in the market.
Seeing Beyond Science: Forecasting with Confidence
Fuld & Company helps clients navigate high-stakes commercialization by seeing beyond science to the full market landscape.
Through scenario mapping, competitive intelligence, and stakeholder insights, we build forecasts that are resilient, dynamic, and actionable.
We enable clients to anticipate disruption, refine forecasts in real time, validate assumptions, and align cross-functional decisions — turning foresight into strategic advantage.
From Prediction to Preparation
In an era where science alone no longer guarantees success, forecasting must evolve from prediction to preparation.
At Fuld & Company, we empower biotech and pharma leaders to turn complexity into clarity — building forecasts that don’t just predict the future but help shape it.
Connect with us to explore how we can support your next strategic move. info@fuld.com
References
- “Failure to launch? Half of drugs rolled out since 2004 didn’t live up to sales forecasts: report” , Fierce Pharma.
- “US emerging pharma and biotech first launches: A story of over- and underperformance” , ZS Associates.
- “Drug launches reflect overall company performance” , Deloitte Insights.
- “Mechanism of Action | ZYNTEGLO™ (betibeglogene autotemcel)” , ZYNTEGLO HCP.
- “ZYNTEGLO™ (betibeglogene autotemcel) | An FDA Approved Gene Therapy” , ZYNTEGLO.
- Whitney, D. et al. “Drug product attributes predict clinical efficacy in betibeglogene autotemcel gene therapy for β-thalassemia.” Molecular Therapy – Methods & Clinical Development, Vol. 31, 101155 (2023).
- “ICER Publishes Final Evidence Report and Policy Recommendations on Beti-Cel Gene Therapy for Beta Thalassemia” , ICER.
- “Bluebird prices gene therapy at 1.58 million euros over 5 years” , Reuters.
Tags: AI & Analytics, BioPharma, Healthcare & Life Sciences, Market Analysis, Market Insights, Medical Devices, Pharmaceuticals, Strategic Planning, Technology & Innovation Research
