Ben Beckley, EmerGENE

A scientific breakthrough like a new cell and gene therapy (CGT) can often be just as frightening as it is exciting to patients—many have developed routines and familiarity with their regimens and a new treatment, however promising, can be a daunting thought. This means life sciences companies in this space must develop strategies to help put the minds of all those involved in the process of providing these therapies at ease.

CGTs have the potential to transform healthcare for patients suffering from a wide range of diseases—offering potentially curative and regenerative treatments. Cell therapies restore or alter certain sets of cells or use cells to carry a therapy through the body. Cells are cultivated or modified outside the body before being injected and can originate from the patient (autologous cells) or a donor (allogeneic cells). Gene therapy aims to treat diseases by replacing, inactivating or introducing genes into cells either 

. Some therapies can be considered both cell and gene as they work by altering genes in specific types of cells and injecting them into the patient.

Due to their promise, the pace of research and development in the field is accelerating quickly. According to the American Society of Gene & Cell Therapy (ASGCT), there were 3,366 gene CGTs in development globally from the preclinical through pre-registration stages as of Q3 2021. CAR T-cell therapies remain the most common technology used in the pipeline of genetically modified cell therapies and of these, 98% are in development for cancer indications.

The complexity, cost and therapeutic approach of manipulating the expression genes is often a route cause of concerns for patients. A 2017 study into patient perspectives on CGT treatments for sickle cell anemia found that cultural beliefs and public misconceptions of the therapy fueled patient fears about treatment.

 This can pose significant challenges when encouraging patients to begin therapy, delaying treatment start dates and often reducing optimal chances of therapy success. Apprehension due to the novelty and lack of infrastructure support for CGTs, as well as cost and efficacy concerns among healthcare providers (HCPs) and insurance providers also present obstacles to therapy referral.

Access to clear, concise, understandable information is essential for patients to feel in control of their healthcare decisions. As for most emerging medicine and treatments, the complexity of CGT lexicon adds to the barrier excluding patient self-learning and delaying treatment uptake. As patients may be critical to the supply chain of their own CGT treatment, this requires a new era of patient support and understanding of the CGT process.

All of these challenges are catalyzed by the availability of accelerated approval pathways for these therapies which started with the Accelerated Approval Program introduced by the FDA in 1992. Additional legislation including the FDA Modernization Act of 1997, the FDA Safety and Innovation Act of 2012 and the 21st Century Cures Act of 2016 provided further expedited approval pathways. There are now five expedited approval designations in the US: fast-track designation, breakthrough therapy, accelerated approval, priority review and regenerative medicine advanced therapy (RMAT) designation. While not guaranteed as part of the designation, advanced therapy medicinal products (ATMPs) may be eligible for priority review and accelerated approval and data shows that these classifications can accelerate chemistry manufacturing control (CMC) programs by more than two years based on mean timeframes (from 7.4, down to 5.2).

 Kite Pharma’s CAR-T therapy Yescarta (axicabtagene ciloleucel) was approved by the FDA just over three years after receiving orphan-drug designation.

With all of this in mind, biopharma companies need to take steps as early as possible to implement CGT infrastructure and strategies to tackle these misconceptions. These measures will ensure that treatment is adopted and prescribed to the patients who stand to benefit from it. The key to achieving this is developing a comprehensive go-to-market strategy right at the beginning of CGT development and in clinical trials.

Organizations developing cell and gene therapies are often confronted with small patient populations, higher mortality rates and a lack of disease state understanding, making it difficult to access and recruit patients and set clinical endpoints in trials.

 seeks to address this by advocating for new clinical trial designs. The argument is that three-phase randomized, controlled clinical trials are unsuitable for CGTs. As such, the guidance advocates for new age trials that are shorter, combining phases to show both safety and efficacy. Later-stage trials will be replaced with rollover studies to see longer-term effects of treatment. Control groups will give way to natural history studies to illustrate what happens when patient groups go untreated, which will also help to identify surrogate endpoints that can serve as early indicators of future outcomes to help expedite trials.

Trial designs must bring sponsors and ATMPs closer to patients and factor in commercialization. It is now understood that market entry strategies should be commenced as early as technology transfer from the lab to Phase I trials. Many CGT companies are navigating this space for the first time and are taking advantage of partners that have extensive experience in the CGT space. Global integrated healthcare services partners can aid in strategizing in all areas impacting CGT development, manufacture and commercialization. The latter, which plays an enormous role in the therapy's commercial success, can encompass anything from pharma sales and HCP engagement to patient support programs and medical communications.

As these novel technologies are in their infancy in terms of commercialization—distribution challenges, training and administration complexities, pricing and reimbursement challenges, as well as administration site accreditation hurdles, all exist. These challenges contribute to HCP referral apprehension, which is further cemented with the shortage of CGT information for HCPs and their patients. HCP apprehension and delay in treatment referral have led to CGT treatment being overlooked or often viewed as a last-resort treatment.

To bring novel solutions forward, the industry and health authorities have to strategize early and innovatively. To ensure optimal CGT treatment referral and uptake, pharma is now prioritizing support services and communication strategies to bridge the knowledge gap and implement the correct infrastructure, enabling early, potentially life-saving intervention for patients.

The pharmaceutical industry needs to apply a different mindset for CGT than for previous treatments. Greater collaboration is needed. Companies must ensure that the overall site onboarding and treatment process is more seamless, efficient and less costly for providers and patients than ever before. A new wave of cell orchestration software vendors, for example, is enabling manufacturers to provide transparency, integration of value chain partners and the choreography of CGT logistics and manufacture—creating a more robust, enhanced service that plays a small part in justifying the often-hefty CGT price tag.

Process standardization and simplification across manufacturers and sites is key to success. An opportunity exists for a coordinated, cooperative approach through the involvement of integrated healthcare services partners that specialize in CGT solutions.

HCPs need help from the industry to place themselves and their patients effectively into the CGT journey.

As with any new therapy, the core question is whether the benefit outweighs the risks and costs. For CGTs, the benefits may not be clearly defined, and the costs involved include high one-time payments and disruptive and complex logistics that completely reimagine linear supply chains. Risk Evaluation and Mitigation Strategies (REMS), as well as accreditation, introduce additional administrative barriers to HCPs and pharma.

Before clinical experience enables predictors of response to complement patient profiles, HCPs must receive strategies and support from pharma and health authorities.

Payers and insurers also see the promise of these revolutionary CGTs; however, they are limited in their ability to act due to a lack of infrastructure and systems to incorporate and fund these on a large scale.

Advisory support for go-to-market planning is now in high demand for CGTs to overcome development and commercialization pitfalls that could lead to apprehension. Patient mapping and payer insight-generation are both needed to create solutions for both the financial and social burden of CGTs. Parallel to the early-stage development of the CGT, HCP treatment choice studies and patient service program benchmarking assessments must take place. Critical analysis of these, with the implementation of ongoing surveillance mechanisms by the industry will shape an effective strategy early in development.

There needs to be a high level of global HCP engagement facilitated through a detailed HCP segmentation and profiling strategy. Detailed patient segmentation and profiling are also critical resources to be provided to HCPs prior to the therapies' entry to market. As the patient's caregiver is a crucial member of a CGT journey, strategies should include emphasis on a caregiver engagement plan, as well as the creation of patient and caregiver education materials. Healthcare service providers acknowledge that a major barrier to overcome will be in CGT pricing, reimbursement and health economics and outcomes research (HEOR).

As well as Congress planning and accreditation planning, organizational preparedness is a necessity to preempt pitfalls and challenges. For regulatory strategy and submissions, a global regulatory approach is required and regulatory interactions must be prioritized early in development. Education and disease awareness is also central to breaking through CGT misconceptions before commercialization.

Despite the potential of CGTs, there remain considerable barriers to the adoption of new treatments. Overcoming concern and apprehension is a significant challenge not only among patients, but HCPs and payers as well, and there is a need for rapid implementation of novel solutions to accelerate the acceptance of these ground-breaking therapies to match the pace of growth in the development pipeline.

Only in developing an in-depth go-to-market strategy to commercialize a new CGT right at the beginning of trials can all hurdles and apprehension be foreseen and overcome. This will propel CGT toward its full potential as a game-changer in disease treatment.

https://asgct.org/global/documents/asgct-pharma-intelligence-quarterly-report-q3-2021.aspx

https://www.raps.org/news-articles/news-articles/2016/3/analysis-breakthrough-therapies-cut-development-timeline-by-two-years

https://www.researchgate.net/figure/Development-timeline-of-axicabtagene-ciloleucel-and-tisagenlecleucel-The-spaces-between_fig1_338977698

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The benefits of establishing an in-depth go-to-market commercialization strategy for a new CGT in the beginning of clinical trials