Taming the Complexity of CGT Commercialization: 5 Keys to a Workable Operating Model

The past two years have tested the cell and gene therapy (CGT) space. While Vertex's Casgevy approval in December 2023 marked a CRISPR milestone, the industry has seen mixed signals since—Takeda’s exit and bluebird bio’s acquisition at a fraction of its potential, even as major investments poured in from AbbVie, Eli Lilly, and AstraZeneca.

There is confidence in the science but uncertainty about who can navigate CGT's unique complexities: small patient populations, high payer switching rates, uncertain long-term outcomes, and supply chains built around patient-specific doses and delivery.

In this article, I discuss five strategic levers that biotechs can use to tackle this complexity. These are based on insights from industry leaders at a recent panel discussion I hosted for Beghou, my notes from October’s Cell and Gene Meeting on the Mesa, and my conversation with Rita Johnson-Greene, COO of the Alliance for Regenerative Medicine (ARM).

These perspectives come from leaders who've launched therapies at Biomarin, Novartis, and Orca Bio, and are particularly relevant now, when regulatory signals, such as the FDA’s recent draft guidance on streamlined pathways for single-arm trials, are creating tailwinds for the sector.

Strategic disease selection

CGT therapies for severe conditions or those with few alternatives see higher commercial success. For instance, Novartis’ Zolgensma, a single-dose therapy offering a potential cure for spinal muscular atrophy, and Kite/Gilead’s treatment Yescarta for certain types of non-Hodgkin lymphoma, have seen strong adoption, while gene therapies for hemophilia have seen slower uptake due to lower urgency and the availability of established therapies.

However, clinical need alone doesn't guarantee commercial viability: The size of the patient population matters, too. It needs to be large enough to justify infrastructure investment and manufacturing scale-up, yet small enough to demonstrate a clear unmet medical need.

In addition, companies are exploring opportunities to use the same platform across multiple therapy targets to improve scalability and address economic viability issues. Applying both clinical and commercial criteria rigorously can sometimes mean walking away from promising science.

When Alan Reine joined Prime Medicine in 2024, the company was spreading its resources across 18 active programs. He led a "value framework exercise" to assess each program's technical, clinical, competitive, and commercial viability.

Eventually, Prime decided to shut down one program despite strong clinical results and pivoted toward liver-targeted diseases, an area where the technology, delivery mechanisms, and regulatory pathways offered the strongest chance of success.

Early, deep patient engagement

True patient-centricity will drive commercial success as CGT moves beyond first-generation therapies. Current timelines in CGT, from diagnosis to treatment, can exceed six months, often compounded by genetic testing backlogs, insurance authorization processes, and complex travel logistics.

According to Emily Chee, former GM at Novartis Gene Therapies, shaving off even one day in therapies for critical diseases can make a huge difference to patient experience and, in turn, to product success. For example, patients sometimes cancel because their disease progresses while they’re waiting for treatment, noted Chris McDonald, SVP and global head of manufacturing at Kite.

“These are really sick patients, and every day counts,” he told MM+M last year.

Optimizing time-to-treatment requires not just understanding but also intercepting the patient journey, according to Rindy Dhillon, former VP of US marketing & operations, Biomarin. She recommended breaking down the path from diagnosis to treatment into stages—demand generation, treatment choice, and access.

Identify bottlenecks at each stage and design interventions (e.g., travel support, streamlined scheduling) to shorten time-to-therapy. That’s one reason former Kite CEO Christy Shaw has compared cell therapy to a “team sport,” with numerous hand-offs between the hospital where a patient’s cells are extracted, to the factory where they’re reengineered, and back again for patient infusion.

During the COVID-19 pandemic, Shaw recalled, the company even employed “a specialist in getting medical supplies into war-torn countries” to navigate supply and travel constraints as it ensured patients with lymphoma were able to receive its therapy.

This redesign should be informed by listening to and learning from the patient community. In our 1:1 conversation, Johnson-Greene of ARM highlighted how, in rare or critical diseases, patient families and caregivers often drive key decisions.

She advocated for transparent, value-based education of this community early in the process and openly celebrating success stories to build trust during a time of uncertainty.

That includes stories that ARM works to amplify, like the SCD patient who took a CRISPR-based gene therapy in 2020 and summited Mt. Kilimanjaro four years later. These speak to the power of CGTs to improve quality of life by addressing the underlying cause, not just symptoms.

It’s a big reason why new hematologic CAR T-cell therapies are three times as likely to earn FDA approval as conventional oncology drugs, according to a 2023 analysis by Tufts Medical Center’s NEWDIGS. For many of these patients, the status quo can mean severe disease or even reduced life expectancy, Johnson-Greene added.

Maximum launch-curve slope

Planning must begin at least three years (or even more) before launch, as compared to the recommended 18-month timeline for traditional therapies. Late-stage trials should be treated as a dress rehearsal for real-world delivery.

For instance, instead of capturing only safety or efficacy, trials can capture operational data about site readiness and feasibility of outpatient delivery, which will shape the launch strategy.

Patient flow can stall in the early stages, especially if only one physician at each treatment center is trained to administer the product, which can affect launch momentum. Launching with multiple physicians at each site ensures steady patient evaluation and prescribing, even when individual providers are unavailable.

That’s a strategy being pursued by chimeric antigen receptor (CAR) T-cell drugmaker Autolus Therapeutics, its CEO said on a second-quarter earnings call.

“An effective CGT operating model requires anticipating patient population growth (e.g., late-stage to early-line) and identifying demand inflection points. Manufacturing will need to scale accordingly, including planning for follow-on indications, new facilities, and FDA certifications,” said Steve Gavel, chief commercial officer, Orca Bio, during the panel discussion.

Agility-centric organizational design

In CGTs, manufacturing timelines can influence clinical trial design, payer feedback can inform product development, and site readiness can shape commercial strategy. Which is why the traditional pharma operating model, with sequential handoffs from R&D to clinical to commercial, will not work.

CGTs demand cross-functional coordination and real-time decision-making, where insights from one area inform others. This requires flatter structures with clear decision rights and fewer approval layers.

Chee pointed out that this is one area in which smaller biotechs have a natural advantage.

"Being in a smaller setting allows you to operate much more nimbly. One way to reduce complexity is to have the right talent and minimize layers. Let people make decisions. Sometimes, organizations assume everyone needs to be at the table. But simplifying roles and responsibilities, and being clear about who owns decisions, is how you really reduce complexity."

How this plays out depends on company size. In smaller biotechs, the entire organization can galvanize around a single launch, while in larger companies, this requires creating dedicated launch squads—small, empowered, cross-functional teams that operate with startup-like autonomy within the broader organization.

Agility ultimately depends on hiring people with the right mindset. Look for people who thrive in ambiguity, question legacy processes, and have experience launching specialized therapies.

Balance deep technical expertise with the ability to "build the plane while flying."

"You have to think very much end-to-end," said Daniel Grant, VP & global program head at Novartis. "That means finding people who understand why commercial and access need to be involved early and why development needs to stay engaged after launch. At the same time, there's a lot of uncertainty, so you need to set expectations for fluidity and change. That mindset shift—embracing both structure and flexibility—is critical for success."

Innovative access solutions

“The biggest tragedy would be if we develop a transformational drug with a clear, large treatment effect, but patients aren't able to get it because we didn't start [the access] process early enough,” Grant added.

For CGTs, access planning must begin early, go deep, and be tailored to the therapy’s unique clinical, economic, and logistical profile. Begin thinking about access as early as first-in-human trials. Internally, align clinical, commercial, and access teams to work on trial design, payer strategy, and site readiness.

Externally, start payer and provider engagement to anticipate reimbursement hurdles and design accessible payment models. As one-time, high-cost interventions, CGTs pose upfront financial risk, uncertain long-term outcomes, and individualized logistics.

Therefore, traditional payment structures will need to be rethought to improve adoption. Explore scalable, payer-friendly models such as value-based contracting and subscription payments that align cost with long-term outcomes.

Even with payer approval, hospitals may struggle with reimbursement under Medicare DRG caps. Coding and billing complexity can be additional barriers.

To solve this, go beyond top-line pricing studies and map site-level economics. Work with hospitals to ensure that payment flows make sense and that providers aren’t financially penalized for offering these therapies.

Taken together, these five levers form a commercialization playbook. Disease selection shapes manufacturing, patient engagement informs trial design, trial learnings feed access strategy, and organizational agility allows companies to adapt as real world constraints emerge.

What makes this particularly promising is that the ecosystem is maturing. Payers are developing sophisticated value-based models and companies are thinking globally.

"There's real opportunity in geographies like APAC and the Middle East, where regulatory bodies have become more flexible and interested in bringing new therapies to match the growing expertise in their regions," said Johnson-Greene, referencing Japan's recent subsidies to CGT-focused CDMOs.

That not only highlights another sign of CGT’s progression but a reason for manufacturers to consider diversifying commercial geography beyond North America and the EU, she suggested. Smaller companies should consider partnering with a larger player experienced in global launches.

At this year's Cell and Gene Meeting on the Mesa, investor conversations reflected this maturation. The question is no longer "Is the science breakthrough-worthy?" but "Can this team execute commercially?"

Investors want to back companies that demonstrate operational foresight across all five levers. CGT commercialization will always be complex. The reason only two blockbuster CGTs remain at this point, according to Deloitte, is hard to pin down.

But the playbook now exists. The regulatory environment is adapting. The infrastructure is being built.

Even though in cell therapies, such as CAR T, only 20% to 30% of eligible patient populations receive the therapy due to a host of reasons, the opportunity is still huge. Consider that 90% of newly diagnosed adult cancer cases are in solid tumors, an area largely untapped by CGT makers but one that’s beginning to draw interest.

Ditto for therapeutic categories like wet age-related macular degeneration, Parkinson’s disease, and diabetes, all of which have attracted promising clinical candidates. For biotechs willing to approach commercialization with the same rigor and innovation as they bring to their science, the future looks bright.

About the Author

Vishal Singal is a partner at Beghou and head of its patient support practice.