Cell and gene therapies: The emerging reality for scalable market readiness

Years of investment have fuelled extraordinary innovation across modalities, delivery systems, and biological targets. Single-dose treatments are already delivering life-altering outcomes for patients with rare genetic diseases, haematological cancers, and conditions once considered untreatable. Zolgensma has transformed spinal muscular atrophy from a leading cause of infant mortality into a treatable condition. CAR-T therapies are producing durable remissions in cancers that previously had no good answer. The science has earned its credibility.

What hasn't kept pace is the model built around it.

The commercialization logic is hitting its limits

For the past decade, CGT has run on a commercialization playbook borrowed from mainstream biopharma: raise capital, scale headcount, burn toward approval, price at the ceiling the market will bear. In oncology and chronic disease, that model has a track record. Costs compress as volume grows. Margins improve. Capital gets its return.

In CGT, those assumptions have repeatedly failed to hold, and the evidence is now hard to ignore.

Capital raised in the sector peaked at $22.7 billion in 2021 and has been restructuring ever since. The money is consolidating into late-stage acquisitions, automation platforms, and proven manufacturing technologies. What it is retreating from is early-stage programs that cannot yet demonstrate how they will be made reliably, priced accessibly, or reimbursed sustainably.

The regulatory picture tells a similar story. Between 2020 and 2024, 74 percent of FDA Complete Response Letters in CGT were driven by manufacturing and quality deficiencies. Around 40 percent of IND submissions are delayed due to inadequate CMC packages; most often in companies that prioritized clinical speed over manufacturing maturity. The spend-to-accelerate model is not just expensive, but it's failing at the regulatory gate, long before therapies reach patients or payers.

Where they do reach payers, the results have been equally instructive. Bluebird Bio withdrew from Europe – not because the therapy didn't work, but because the cost structure required to develop it could not be reconciled with what health systems were willing or able to absorb. Dendreon, the pioneer of autologous cell therapy, built manufacturing infrastructure ahead of demand, found adoption slower than forecast, and went bankrupt.

The structural problem runs deeper than manufacturing or regulation alone. CGT price tags were set to recoup the cost of a development model designed for ultra-rare diseases with tiny patient populations. That logic made sense when eligible populations numbered in the hundreds. As CGT moves into earlier lines of treatment and larger indications, where patient populations number in the tens of thousands, those price points become mathematically impossible for health systems to absorb.

Outcomes-based agreements and annuity structures are emerging as partial solutions, but they remain fragile and inconsistently adopted. The private insurance market in the US has its own structural problem: patients change insurers, so no single payer wants to absorb the full cost of a one-time cure whose long-term benefit accrues elsewhere. The commercial logic was built for a different kind of medicine. It has not been rebuilt for what CGT is becoming.

Meanwhile, a different model is demonstrating a different cost-to-learning ratio. China now initiates more clinical trials than any other single region, surpassing North America and Europe combined in 2025. This is driven not by venture capital but by investigator-initiated trials, state-backed infrastructure, and integrated hospital networks that generate clinical knowledge at a fraction of the cost Western development programs require. We’re not only looking at a lower-cost version of the same model, but rather a structurally different approach to how clinical evidence gets built and manufacturing capability gets developed alongside it.

What sustainable commercialisation actually requires

The organizations that will shape CGT over the next two decades are not necessarily the best-funded. They are the ones that redesign the commercialization logic and do it before the current model exhausts the goodwill, capital, and patience that CGT has spent a decade accumulating.

That redesign has three components:

Manufacturing as a strategic asset

Manufacturing must be treated as a strategic asset from day one, not an execution problem to be solved after approval. Early investment in scalable platforms, automation, and digital quality systems is what separates programs that survive regulatory scrutiny from those that don't.

Multiply Labs demonstrated a 74 percent cost reduction and hundred-fold throughput improvement through robotic automation of cell therapy manufacturing. This is proof that redesigning the manufacturing logic changes the economics, not just the efficiency. Modular, flexible infrastructure that scales with demand rather than ahead of it avoids the overbuild trap that destroyed Dendreon. It is the right facility at the right time, designed to grow.

Regulatory strategy front-loaded, not retrofitted

BridgeBio invested early in scalable manufacturing platforms, engaged regulators around validated clinical endpoints, and secured RMAT designation. This positioned its program for expedited review and a smoother path to commercialization. The contrast with programs that prioritize clinical speed and pay for manufacturing immaturity at the submission stage is stark. Proactive regulatory engagement, aligned on trial design, CMC controls, and long-term safety monitoring from the outset, is not slower. It is faster, because it avoids the costly remediation that derails programs at the point they can least afford it.

Value, access, and reimbursement strategy built in from start

Access and reimbursement strategies must be built into commercial planning from the start, rather than bolted on at launch. Luxturna demonstrated that early payer engagement, outcomes-based rebate programmes, and instalment-based payment structures can turn a high-cost therapy into a broadly accessible one. Bluebird demonstrated the alternative: a strong therapy, a weak reimbursement narrative, and a market exit. As CGT expands beyond ultra-rare indications, the value story must be constructed with the same rigour as the clinical programme. Innovative payment models are not optional features of a commercial strategy. They are the commercial strategy.

The next twenty years will be defined by choices made now

A new PA report explores four plausible futures for the sector shaped by two critical uncertainties: how far modalities shift toward scalable versus personalized approaches, and how equitable access is distributed across geographies and health systems. Each scenario carries different implications for how manufacturers, developers, CDMOs, regulators, and payers should position themselves today.

Across all four scenarios, one thing is consistent: the organizations that act now, investing in scalable platforms, building regulatory and CMC strength early, and constructing access models that health systems can actually absorb, will be best placed to succeed. They will determine whether CGT fulfils its promise as a sustainable pillar of modern medicine, or remains an exceptional intervention constrained by a commercialization model that was never designed to carry it this far.

The next chapter of CGT will not be written by breakthroughs alone. It will be written by leaders who are willing to rethink not just the science, but the system built around it.

This article was first published in Cell and Gene.