Cell and gene therapies (CGTs) have come a long way, and I’ve watched in awe as biotech companies have brought therapies to patients that they could previously only dream of.
At the same time, in my time leading a platform that helps facilitate conferences and other gatherings for those working with CGTs, I've watched too many promising programs flounder; not because of the science but due to a disconnect between developers and the gatekeepers of market access: the regulators and payers. This observation is something I touched on in my previous piece on funding and ecosystem pressures in advanced therapies.
But globally, and particularly in the U.S., new frameworks are creating genuine opportunities for earlier collaboration. Ultimately, success depends on developers rethinking how they engage decision-makers.
Understanding The Disconnect
Part of the challenge is that CGTs face unique constraints in moving from bench to bedside: Small patient populations make large-scale trials impractical or impossible, one-time curative therapies don’t fit the standard evidence or value assessment models built for chronic disease treatments and, ultimately, these therapies are very expensive.
These aren’t traditional drugs, so the traditional approach of developing, seeking approval, then negotiating coverage simply doesn’t work. The existing systems simply weren't designed for this level of complexity and pace of innovation.
Regulators Are Responding
Fortunately, regulators are recognizing and responding to this challenge. Instead of acting as gatekeepers at the end of the process, many want to be partners from the start. In late 2025 alone, we saw three major shifts that demonstrate this:
- The U.S. Food and Drug Administration (FDA) is rethinking how clinical trials are designed for small patient populations. The FDA guidance finalized in September encourages consideration of innovative clinical trial designs for CGTs in small populations and urges sponsors to discuss these with the FDA early on.
- The FDA is also opening the door to new approval pathways for ultra-rare disease therapies. Particularly for life-threatening conditions with no alternatives, the FDA is willing to approve treatments based on robust mechanistic rationale and a few well-documented cases with long-term follow-up. Announced in November, this "plausible mechanism" pathway for personalized therapies strongly incentivizes early, iterative engagement.
- The U.K.'s Medicines and Healthcare products Regulatory Agency (MHRA) is overhauling its regulatory framework to better support rare disease innovation. MHRA committed in November to a “bold new rulebook” to get rare disease therapies tested and approved faster, with more science-led, flexible pathways and integrated safety monitoring. The proposals explicitly build on years of dialogue with developers and patients.
The Reimbursement Challenge
But regulatory approval is only half the battle. Payers—insurers, government health systems—ultimately decide whether patients can access an approved therapy. For CGTs, I find this is often the toughest obstacle.
Perhaps naturally, payers' first look is at the price tag. CGTs are expensive, and unavoidably so. These therapies cost millions to produce, with manufacturing and labor costs high and small production volumes not presenting economies of scale.
Therefore, manufacturing cost-effectiveness is now a central concern for both investors and payers; developers are expected to explain how they will bend cost of goods sold (COGS) curves over time. A brilliant therapy that can't be manufactured affordably won't attract funding and won't be reimbursed at sustainable levels.
Payers also struggle with how to value one-time curative treatments like CAR-T cell cancer therapies. These models are built around the cost per year of therapy. A single treatment with decades of benefit doesn't fit the standard equation. Payers are seeking long-term durability and safety data to justify such large upfront payments.
Some payers are experimenting with outcomes-based agreements and amortization models. In September 2025, the U.S. CMS launched the CGT Access Model, the first time the federal government has negotiated outcomes-based agreements for CGTs on behalf of state Medicaid programs, starting with sickle cell disease therapies. Yet most commercial payers have yet to catch up, still using frameworks designed for small-molecule drugs.
Bridging The Gap
The encouraging news is that I see a willingness from all sides to overcome the disconnect. Again, a more collaborative, co-design model is emerging where developers, regulators and payers work together from the outset. Toward this, here are some considerations and practical ways companies can align early with regulators and payers.
- The FDA wants to be involved in trial design, not just the evaluation of completed studies. Companies that engage early can shape evidence generation to fit the new pathways. This prevents late-stage surprises that delay approval or require additional studies.
- Evidence that satisfies regulators doesn't always satisfy payers. Again, talking to payers early can help design trials that serve both purposes. This might mean including quality-of-life measures, cost-effectiveness endpoints or longer follow-up periods that payers need for coverage decisions. Some developers resist early payer engagement, worried about showing their hand. But I think payers shouldn’t be viewed as adversaries. They want effective therapies they can afford to cover. Early dialogue can help align expectations.
- Manufacturing economics need to be a priority from the start. Companies that see these considerations as putting the cart before the horse tend to struggle with both investors and payers. This doesn't mean compromising on quality, but it does mean designing processes that can be scaled and optimized while maintaining product integrity.
In my experience, the most meaningful progress emerges when stakeholders can speak candidly. Conference attendees frequently tell me how valuable it is to directly test pricing and outcomes assumptions and learn from access strategies that have succeeded for their peers.
Keep Talking, Keep Listening
I'm optimistic because I see these approaches working. The regulatory frameworks in the U.S. are helping create real opportunities for collaboration. Payers are showing more willingness to engage early and consider innovative coverage models. Developers, often working with highly skilled service providers within the CGT ecosystem, are starting to recognize that early engagement pays off.
This ecosystem succeeds when developers, regulators and payers work as partners with a shared mission. Extraordinary science has brought us this far, but access shouldn’t feel extraordinary. The biggest breakthrough will be when stories of patients receiving life-changing CGTs are no longer remarkable but routine. The only way we’ll get there is to keep the conversation going—engaging early and often across the ecosystem.
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