gene therapy research paper

• The first peer-reviewed journal in the field of human gene therapy, providing all-inclusive coverage of the research, methods, and clinical developments that are driving today's explosion of gene therapy advances.
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Human Gene Therapy

Editor-in-Chief: Terence R. Flotte, MD Deputy Editor-in-Chief: Guangping Gao, PhD European Editor: Hildegard Büning, PhD Asian Editor : Yu-Quan Wei MD, PhD Deputy Editors: Mark Kay, MD, PhD, Thierry VandenDriessche, PhD, and Cheng Seng, PhD

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Aims & Scope

Human Gene Therapy   (HGT) is the premier, multidisciplinary journal covering all aspects of gene therapy. The Journal publishes important advances in DNA, RNA, cell and immune therapies, validating the latest advances in research and new technologies. Established in 1990, HGT  provides a prestigious forum for publishing scientific and clinical research, including ethical, legal, regulatory, social, and commercial issues, which enables the advancement and progress of therapeutic procedures leading to improved patient outcomes, and ultimately, to curing diseases. HGT publishes 12 double issues per year, including sections on Methods (product testing and development) and Clinical Development (regulatory review, toxicology and commercial development). The journal also publishes a wide range of reviews, commentaries and editorials.

• Basic and clinical advances in gene therapy
• Delivery systems
• Cell therapy
• Immunotherapy
• Clinical genome editing
• Small nucleic acid therapeutics, including RNAi
• Clinical trials (including confirmatory or negative results)
• Improvements in vector developments
• Animal models
• Pre-clinical animal/in vitro studies to assess safety of gene and cell therapy products
• Clinical protocols
• Commercial development of gene and cell therapy products

Human Gene Therapy  was the first journal devoted to cover the field of gene therapy.

Human Gene Therapy is under the editorial leadership of Editor-in-Chief Terence R. Flotte, MD, University of Massachusetts Medical School and other leading investigators. View the entire editorial board .

Audience: Geneticists, medical geneticists, molecular biologists, virologists, experimental researchers, and experimental medicine specialists, among others.

Human Gene Therapy and HGT Methods provide “Instant Online” publication 72 hours after acceptance

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The Official Journal of nine international societies:

Special Issue: Inflammation Networks in Gene Therapy

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Re:GEN Open

Nucleic Acid Therapeutics

The CRISPR Journal

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Recent Progress of Machine Learning in Gene Therapy

Affiliations.

• 1 Department of Computer Science, Pacific Lutheran University, Tacoma, WA, United States.
• 2 Department of Physics, Pacific Lutheran University, Tacoma, WA, United States.
• 3 Department of Mathematics, Pacific Lutheran University, Tacoma, WA, United States.
• 4 Department of Humanities, Pacific Lutheran University, Tacoma, WA, United States.
• 5 Division of Computing Software Systems, University of Washington-Bothell, Bothell, WA, United States.
• 6 Department of Computer Science, Saint Louis University, St. Louis, MO, United States.
• 7 School of Life Science and Technology and Center for Informational Biology, University of Electronic Science and Technology of China, Chengdu, China.
• PMID: 34161210
• DOI: 10.2174/1566523221666210622164133

With new developments in biomedical technology, it is now a viable therapeutic treatment to alter genes with techniques like CRISPR. At the same time, it is increasingly cheaper to perform whole genome sequencing, resulting in rapid advancement in gene therapy and editing in precision medicine. Understanding the current industry and academic applications of gene therapy provides an important backdrop to future scientific developments. Additionally, machine learning and artificial intelligence techniques allow for the reduction of time and money spent in the development of new gene therapy products and techniques. In this paper, we survey the current progress of gene therapy treatments for several diseases and explore machine learning applications in gene therapy. We also discuss the ethical implications of gene therapy and the use of machine learning in precision medicine. Machine learning and gene therapy are both topics gaining popularity in various publications, and we conclude that there is still room for continued research and application of machine learning techniques in the gene therapy field.

Keywords: CRISPR; Machine learning; cancer; cardiovascular disease; ethics; gene therapy; hemophilia; neurodegenerative disease.

Copyright© Bentham Science Publishers; For any queries, please email at [email protected].

• Artificial Intelligence*
• Genetic Therapy
• Machine Learning*
• Precision Medicine

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Recent advances in gene therapy: genetic bullets to the root of the problem

• Review Article
• Published: 25 October 2022
• Volume 23 , pages 1107–1121, ( 2023 )

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• Mohsen Danaeifar 1  

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Genetics and molecular genetic techniques have changed many perspectives and paradigms in medicine. Using genetic methods, many diseases have been cured or alleviated. Gene therapy, in its simplest definition, is application of genetic materials and related techniques to treat various human diseases. Evaluation of the trends in the field of medicine and therapeutics clarifies that gene therapy has attracted a lot of attention due to its powerful potential to treat a number of diseases. There are various genetic materials that can be used in gene therapy such as DNA, single- and double-stranded RNA, siRNA and shRNA. The main gene editing techniques used for in vitro and in vivo gene modification are ZNF, TALEN and CRISPR-Cas9. The latter has increased hopes for more precise and efficient gene targeting as it requires two separate recognition sites which makes it more specific and can also cause rapid and sufficient cleavage within the target sequence. There must be carriers for delivering genes to the target tissue. The most commonly used carriers for this purpose are viral vectors such as adenoviruses, adeno-associated viruses and lentiviruses. Non-viral vectors consist of bacterial vectors, liposomes, dendrimers and nanoparticles.

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Special issue: Genome editing and gene therapy

Gene Therapy Approaches Toward Biomedical Breakthroughs

Non-viral vectors for gene-based therapy

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Danaeifar, M. Recent advances in gene therapy: genetic bullets to the root of the problem. Clin Exp Med 23 , 1107–1121 (2023). https://doi.org/10.1007/s10238-022-00925-x

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Received : 08 April 2022

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Published : 25 October 2022

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DOI : https://doi.org/10.1007/s10238-022-00925-x

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Safety and Effectiveness of Gene Therapy

Andrew P. Byrnes, Ph.D.

Office of Tissues and Advanced Therapies Division of Cellular and Gene Therapies Gene Transfer and Immunogenicity Branch

[email protected]

Chief, Gene Transfer and Immunogenicity Branch

BS, MS, Yale University, Department of Molecular Biophysics and Biochemistry

PhD, Oxford University, Department of Human Anatomy

Postdoctoral Fellow, Johns Hopkins University, School of Hygiene and Public Health

General Overview

Gene therapy holds great promise for treating cancer, inherited disorders, and other diseases. Gene therapy uses carriers called 'vectors' to deliver genes to tissues where they are needed. Researchers are currently investigating the safety and effectiveness of a variety of different gene therapy vectors in hundreds of clinical trials in the US.

We are studying one type of commonly-used gene therapy vector that is made from a disabled cold virus -- the adenovirus vector. While adenovirus vectors are very efficient at delivering genes, adenovirus vectors are not always easy to target to the correct tissue. In addition, adenovirus vectors can cause toxic effects that limit the amount of vector that doctors can give to patients. We are particularly interested in how to safely deliver large amounts of adenovirus vectors intravenously, with the goal of specifically targeting tumors and other tissues.

New adenovirus gene therapy vectors are tested in animals before human clinical trials begin, and it is important for both researchers and the FDA to know how well these animal studies can predict safety. Thus, another of our major goals is to develop animal models that reliably predict the safety and effectiveness of adenovirus vectors in humans.

Our studies will help us to understand the mechanisms for adenovirus vector targeting and toxicity, and the relevance of animal models to human outcomes. This new knowledge will enable researchers to design safer and more effective gene therapy vectors.

Scientific Overview

Adenovirus (Ad) vectors have shown considerable promise in animal models and are currently being used in numerous clinical trials, especially for the therapy of cancer. We are interested in improving the safety and efficacy of Ad vectors, especially when administered through the vascular system. Certain properties of Ad vectors make them hazardous to administer intravenously in large doses, and our laboratory is trying to understand and fix this problem.

One of our major areas of interest is the innate immune response to Ad vectors. These rapid responses can cause serious toxicity and may severely limit the doses of Ad vectors that are safe to use. In addition, we are also studying how cells in the liver such as Kupffer cells and hepatocytes recognize Ad, since the liver is the major site at which Ad vectors are cleared from the circulation. A better understanding of these mechanisms will help us to develop strategies to improve vector efficacy and reduce toxicity. We will also gain a better understanding of the advantages and disadvantages of using different animal species to predict the behavior of Ad vectors in humans, which is particularly relevant to the regulatory work of the FDA.

Recent work from our lab and others has shown that Ad vectors are heavily influenced by plasma proteins that rapidly opsonize the vectors after intravenous injection. We found that natural IgM antibodies bind to Ad vectors, activate complement, and reduce liver transduction. Intriguingly, the Ad hexon protein specifically binds to coagulation factor X (FX), and we found that recruitment of FX by Ad vectors protects them against neutralization by complement. These findings show that Ad vectors recruit a number of plasma proteins that interact in complex ways with each other and with cells, and that these host proteins ultimately help to determine whether the vector successfully reaches its target.

In the long run, a better fundamental understanding of Ad vector biology will facilitate the design of safer Ad vectors that are easier to target. Better animal models will be important for testing novel vectors for safety and efficacy.

Publications

• PLoS Pathog 2022 Sep 26;18(9):e1010859 Binding of adenovirus species C hexon to prothrombin and the influence of hexon on vector properties in vitro and in vivo. Tian J, Xu Z, Moitra R, Palmer DJ, Ng P, Byrnes AP
• FEBS Lett 2019 Dec;593(24):3449-60 Interaction of adenovirus with antibodies, complement and coagulation factors. Allen RJ, Byrnes AP
• PLoS One 2018 Feb 5;13(2):e0192353 Hexons from adenovirus serotypes 5 and 48 differentially protect adenovirus vectors from neutralization by mouse and human serum. Harmon AW, Moitra R, Xu Z, Byrnes AP
• Methods Mol Biol 2017;1643:187-96 Evaluating the impact of natural IgM on adenovirus Type 5 gene therapy vectors. Xu Z, Tian J, Harmon AW, Byrnes AP
• J Control Release 2016 Aug 10;235:379-92 Substitution of blood coagulation factor X-binding to Ad5 by position-specific PEGylation: Ppeventing vector clearance and preserving infectivity. Krutzke L, Prill JM, Engler T, Schmidt CQ, Xu Z, Byrnes AP, Simmet T, Kreppel F
• J Virol 2015 Mar;89(6):3412-6 Impact of natural IgM concentration on gene therapy with adenovirus type 5 vectors. Qiu Q, Xu Z, Tian J, Moitra R, Gunti S, Notkins AL, Byrnes AP

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Baby born deaf can hear after breakthrough gene therapy

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A baby girl born deaf can hear unaided for the first time, after receiving gene therapy when she was 11 months old at Addenbrooke’s Hospital in Cambridge.

Gene therapy has been the future of otology and audiology for many years and I’m so excited that it is now finally here Manohar Bance

Opal Sandy from Oxfordshire is the first patient treated in a global gene therapy trial, which shows 'mind-blowing' results. She is the first British patient in the world and the youngest child to receive this type of treatment.

Opal was born completely deaf because of a rare genetic condition, auditory neuropathy, caused by the disruption of nerve impulses travelling from the inner ear to the brain.

Within four weeks of having the gene therapy infusion to her right ear, Opal responded to sound, even with the cochlear implant in her left ear switched off.

Clinicians noticed continuous improvement in Opal’s hearing in the weeks afterwards. At 24 weeks, they confirmed Opal had close to normal hearing levels for soft sounds, such as whispering, in her treated ear.

Now 18 months old, Opal can respond to her parents’ voices and can communicate words such as “Dada” and “bye-bye.”

Opal’s mother, Jo Sandy, said: “When Opal could first hear us clapping unaided it was mind-blowing - we were so happy when the clinical team confirmed at 24 weeks that her hearing was also picking up softer sounds and speech. The phrase ‘near normal’ hearing was used and everyone was so excited such amazing results had been achieved.”

Auditory neuropathy can be due to a variation in a single gene, known as the OTOF gene. The gene produces a protein called otoferlin, needed to allow the inner hair cells in the ear to communicate with the hearing nerve. Approximately 20,000 people across the UK, Germany, France, Spain, Italy and UK and are deaf due to a mutation in the OTOF gene.

The CHORD trial, which started in May 2023, aims to show whether gene therapy can provide hearing for children born with auditory neuropathy.

Professor Manohar Bance from the Department of Clinical Neurosciences at the University of Cambridge and an ear surgeon at Cambridge University Hospitals NHS Foundation Trust is chief investigator of the trial. He said:

“These results are spectacular and better than I expected. Gene therapy has been the future of otology and audiology for many years and I’m so excited that it is now finally here. This is hopefully the start of a new era for gene therapies for the inner ear and many types of hearing loss.”

Children with a variation in the OTOF gene often pass the newborn screening, as the hair cells are working, but they are not talking to the nerve. It means this hearing loss is not commonly detected until children are 2 or 3 years of age – when a delay in speech is likely to be noticed.

Professor Bance added: “We have a short time frame to intervene because of the rapid pace of brain development at this age. Delays in the diagnosis can also cause confusion for families as the many reasons for delayed speech and late intervention can impact a children’s development.”

“More than sixty years after the cochlear implant was first invented – the standard of care treatment for patients with OTOF related hearing loss – this trial shows gene therapy could provide a future alternative. It marks a new era in the treatment for deafness. It also supports the development of other gene therapies that may prove to make a difference in other genetic related hearing conditions, many of which are more common than auditory neuropathy.”

Mutations in the OTOF gene can be identified by standard NHS genetic testing. Opal was identified as being at risk as her older sister has the condition; this was confirmed by genetic test result when she was 3 weeks old.

Opal was given an infusion containing a harmless virus (AAV1). It delivers a working copy of the OTOF gene and is delivered via an injection in the cochlea during surgery under general anaesthesia. During surgery, while Opal was given the gene therapy in right ear, a cochlear implant was fitted in her left ear.

James Sandy, Opal’s father said: “It was our ultimate goal for Opal to hear all the speech sounds. It’s already making a difference to our day-to-day lives, like at bath-time or swimming, when Opal can’t wear her cochlear implant. We feel so proud to have contributed to such pivotal findings, which will hopefully help other children like Opal and their families in the future.”

Opal’s 24-week results, alongside other scientific data from the CHORD trial are being presented at the American Society of Gene and Cell Therapy (ASGC) in Baltimore, USA this week.

Dr Richard Brown, Consultant Paediatrician at CUH, who is an Investigator on the CHORD trial, said: “The development of genomic medicine and alternative treatments is vital for patients worldwide, and increasingly offers hope to children with previously incurable disorders. It is likely that in the long run such treatments require less follow up so may prove to be an attractive option, including within the developing world. Follow up appointments have shown effective results so far with no adverse reactions and it is exciting to see the results to date.  

“Within the new planned Cambridge Children’s Hospital, we look forward to having a genomic centre of excellence which will support patients from across the region to access the testing they need, and the best treatment, at the right time.”

The CHORD trial has been funded by Regeneron. Patients are being enrolled in the study in the US, UK and Spain.

Patients in the first phase of the study receive a low dose to one ear. The second phase are expected to use a higher dose of gene therapy in one ear only, following proven safety of the starting dose. The third phase will look at gene therapy in both ears with the dose selected after ensuring the safety and effectiveness in parts 1 and 2. Follow up appointments will continue for five years for enrolled patients, which will show how patients adapt to understand speech in the longer term.

In Cambridge, the trial is supported by NIHR Cambridge Clinical Research Facility and NIHR Cambridge Biomedical Research Centre.

Adapted from a press release from CUH

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Eight imperatives for launching cell and gene therapies

Recent launches of new cell and gene therapies (CGTs) have yielded mixed results. In some cases, patient outcomes have been promising, with high rates of therapeutic success and transformed lives. In others, the desired therapeutic gains have been undercut by the difficulty of getting the right therapy to the right patients.

Few CGTs have reached the market over the past decade. However, judging from the pipeline of products in Phase III clinical trials, the number of approvals is likely to rise dramatically in the near future. In 2024 alone, up to 21 cell therapy launches and as many as 31 gene therapy launches—including more than 29 adeno-associated virus (AAV) therapies—are expected (Exhibit 1). 1 Evaluate Pharma August 2022 data, Evaluate Ltd.; US Food and Drug Administration.

Companies have worked hard  to develop these exciting new products. 2 Emily Capra, Jeff Smith, and Guang Yang, “ Gene therapy coming of age: Opportunities and challenges to getting ahead ,” McKinsey, October 2, 2019. It behooves them to launch those products effectively so that the therapies can benefit as many patients as possible while ensuring a sufficient return on manufacturers’ investments—thereby encouraging continued research and development in CGT.

CGTs face steeper challenges at launch than traditional drugs do, potentially limiting their adoption and thus their potential to transform patients’ lives. In an environment in which the population of prospective patients for these therapies is small—and where patients frequently switch payers (at least in the United States)—the current payer system is not well suited to accommodate single-dose therapies for which long-term treatment efficacy, risk–benefit ratios, and safety remain uncertain.

Moreover, CGT patients face a highly complex and costly path to treatment, including long trips to widely spaced healthcare sites and frequent genetic testing and counseling. For healthcare providers, finding and training personnel at new sites requires significant investments of time and the development of new relationships with clinicians and administrators. Furthermore, payers can be reluctant to take on the increased financial risk inherent in treatments with higher one-time costs. Finally, companies themselves face considerable supply chain, manufacturing, and distribution challenges in the effort to make sure just-in-time doses are available when and where they are needed.

Would you like to learn more about our Life Sciences Practice ?

To overcome these obstacles, companies planning for future launches must rethink their go-to-market models, moving away from the models they’ve long used for traditional drug launches. This shift requires adequate preparation to ensure that potential patients, providers, and payers are in place; payment and risk-sharing mechanisms between pharmaceutical companies and providers have been established; and the therapy itself is readily available.

Drawing on our work across several recent CGT launches, as well as on interviews with experts and recent roundtables with experienced launchers, we have identified eight priorities that can significantly improve the likelihood that CGT launches will succeed. These priorities fall into three overarching categories: preparing the market, the product, and the company itself (Exhibit 2).

Preparing the market

The sheer novelty of CGTs means that companies cannot rely on past methods of launching new drugs. Instead, they should prepare patients, caregivers, payers, and healthcare systems for the complexity of new CGTs.

1. Identify appropriate sites of care

Traditional drug launches typically follow a prescriber-based approach, with treatment decisions for prescriptions made in a variety of local and community settings. Given the complexity and preparation needed for the typical CGT, the go-to-market model should shift to centralized sites of care—regional, specialized centers with the ability to make treatment recommendations to the right patients and to scale up CGT delivery to them.

Patients living within 60 miles of sites offering gene therapy are more than twice as likely to receive therapy, according to McKinsey analysis of data from Compile, a data provider for the healthcare industry. Locations should thus be carefully chosen to maximize patient concentration. Ensuring complete care models with clear roles and standardized practices can help sites manage the burden of preparing patients and providing care.

A well-functioning site-of-care model depends on three factors: site willingness, capabilities, and scalability. The first is a function of the attitude of site leaders (including both physicians and administrators) toward CGT and their perspectives on local demand for CGT. The second requires drug companies to carefully track the ability of prospective sites to run their first patients through its system; simple checklists for the infrastructure needed to provide therapy will allow companies to quickly determine a site’s suitability. The third requires that prospective sites have the capacity to meet patient and caregiver demand for CGTs (for more on these requirements, see sidebar “Equipping the front lines”).

Equipping the front lines

Site identification, certification , and preparation can take longer for cell and gene therapies (CGTs) than for traditional drugs, in part because these advanced treatments are a first for many potential locations. A large global pharma company recently engaged us to develop a site network strategy for an allogenic cell therapy with a short shelf life. A review of ten CGT launches helped us align on several site selection criteria. These included research and clinical experience, the ability to meet certification requirements, and familiarity with out-of-state Medicaid requirements (given the need for some patients to cross state lines to access care). With these filters, we identified a discrete set of potential treatment centers.

The CGT launches used for comparison also helped inform the sequence and timing of site preparation. After adapting to our unique launch context, we were able to estimate various time frames for the launch: approximately 12 months for site activation planning, six months for protocol review, three months for provider training dry runs, and three months for billing readiness. The outcome of our project was a comprehensive site network plan that included approximately 30 initial target sites, 30 expansion sites, and a clear road map for site certification and readiness.

2. Support patients and caregivers

Providing CGTs to patients typically requires a highly complex, often multiyear journey, so it is essential that both patients and their caregivers understand the process through well-designed patient services and associated infrastructure. Rather than offering standard information hotlines and patient-facing websites, some companies are providing personalized nurse educator programs and regular one-to-one patient outreach along with documentation to monitor the progress of each therapy and to ensure routine follow-up care. To support patients and caregivers with logistics and travel, some companies are now offering travel concierge services with full reimbursement of costs.

Identifying patients who would benefit most from CGT is also important given that CGTs are typically designed for rare diseases. Real-world evidence (RWE) collected both prior to and after launch—including insurance claims, lab data, diagnostic codes, and claims for other medications that potential patients are taking—can help providers discover likely patients and optimize their care. For example, by using natural-language processing and key words from electronic medical records and insurance claims, companies can identify pockets of potential patients and tailor physician outreach accordingly.

In general, each CGT patient has a unique set of needs. Some will require a full suite of services, while others may need only limited support, as with conventional therapies. The key lies in understanding each patient’s individual needs and delivering personalized support.

Each CGT patient has a unique set of needs. The key lies in understanding each patient’s individual needs and delivering personalized support.

3. Offer innovative payment structures

To enable access to and reimbursement for CGTs, companies are experimenting with novel outcomes-based pricing models. These models include the following:

• Outcomes-based payments. The payer covers a fraction of the full price up front and pays the remainder if the therapy achieves prespecified outcomes. One cell therapy company explored this method in the United States, arranging for payment only if a response was achieved after 30 days.
• Outcomes-based rebates. The payer pays the full price of the drug up front but receives a rebate if the drug fails to achieve prespecified outcomes within a predefined period. A US company providing a new gene therapy offered outcomes-based rebates to payers based on both short-term efficacy (30 to 90 days) and long-term durability (30 months).
• Outcomes-based annuity. The payer pays a fixed price, with payments spread over many installments, but only if the drug continues to meet certain prespecified outcomes. A US company launching a new gene therapy used this model to arrange outcomes-based payments for up to five years.

Gene therapy coming of age: Opportunities and challenges to getting ahead

Companies should consider engaging early with payers and sites of care to design the most suitable payment model. Enabling outcomes-based models usually requires involving intermediaries, such as pharmaceutical distributors, that can act as a risk-sharing vehicle, as well as writing a complex set of contracts. In the case of one gene therapy launch, the market access team began holding monthly meetings with payers three years before approval to educate them on the disease and the therapy. By engaging early with payers and providers on payment models, companies can get a head start on assessing the cost–benefit ratio of the CGT they plan to launch.

Preparing the product

A successful CGT launch will also depend on providing full support for the therapy itself by offering evidence-based information to providers and payers and delivering adequate supplies of the therapy.

4. Demonstrate long-term outcomes

RWE can address a range of unique challenges faced by CGT stakeholders. For instance, it can help provide payers with early visibility into the total health system costs related to a particular disease. This is especially important for CGTs because the disease burden is often not quantified for rare subpopulations indicated for CGT. Suitable price anchors and comparisons also may not exist due to a poor or missing standard of care. Some companies are using RWE to quantify the impact of specific diseases across mortality, morbidity, and financial measures, as well as to track long-term outcomes of patients using their therapy, thereby providing payers with the data needed to engage in outcomes-based contracts. Tactically, this can be achieved by identifying the drivers of each outcome measure and then using machine learning to extract the causal relationships between the disease and outcomes.

5. Optimize the supply chain

Given the uncertainties of the CGT supply chain, manufacturing capacity 3 Emily Capra, Andrea Gennari, Alberto Loche, and Carolin Temps, “ Viral-vector therapies at scale: Today’s challenges and future opportunities ,” McKinsey, March 29, 2022. should be matched carefully with demand so that patient-specific doses are delivered just in time to sites of care. To do so, companies should carry out dynamic, scenario-based demand forecasting, beginning as early as three years before the actual launch. If done well, a digital supply chain thread can provide track-and-trace data on critical information (such as the location and quality of cells extracted from patients for autologous cell therapies), demonstrate outcomes, provide timely information regarding when caregivers should bring patients in for treatment, and help automate key steps along the value chain.

Preparing the company

Companies should consider preparing themselves for successful CGT launches, reconsidering their go-to-market models across all potential markets, and updating their organizational models for efficiency and scale.

6. Rethink the go-to-market model

A team effort.

We recently supported an allogeneic cell therapy company in its effort to define its go-to-market model for a therapy that was indicated for an extremely rare disease found across a fragmented provider landscape. Success required seamless coordination across therapy education, cell selection, and reimbursement support. The process leading up to providing the therapy also required providers to transmit patient-specific information so the company could identify the exact version of the therapy for each patient.

Given this complexity, a traditional pharmaceutical field force would likely fall short. To design a model that met the unique needs of the product, we worked together to outline the activities required at each step of the patient, provider, and cell journeys. From there, we landed on priority roles, including a cell selection team, account executives, case managers, and a medical-information team. Governed by well-defined collaboration rules, these teams met the needs of all the stakeholders—patients, providers, and payers—while successfully protecting the personal information of each patient.

Across the patient journey, patients and caregivers face a more complex path with CGT than with traditional therapies. Companies looking to fully support patients along the journey will need to create new CGT-specific roles. For example, appointing CGT account coordinators who can serve as single representatives to site leaders can help build the necessary business relationships between the company and CGT site physicians and administrators. CGT coordinators can also ensure proper synchronization between apheresis—when the cells are extracted from patients—and when the cells are reinfused during therapy. Network coordinators can work with hospital networks and manage referrals to facilitate patient and data flow from one site of care to another as patients move. Across all field roles, tight cross-functional coordination is required to streamline the experience for patients, caregivers, and sites (see sidebar “A team effort”).

7. Enable and promote access across regions

When preparing to launch CGT internationally, companies should consider several areas. First, they need to prioritize markets carefully, considering several factors: the number of potential patients, how patients are treated, how treatments are reimbursed, and whether the infrastructure exists to provide care. This can include the availability of sites equipped to provide therapies and the sophistication of the cold chain for transport of therapies.

Second, companies should determine which model works best for which country: going direct, entering via a partnership, using licensing agreements, or some other arrangement. The model should consider the potential for clustering countries together and the dynamics of extraregional hubs. A regional headquarters with at-scale medical and commercial resources in Singapore, for example, could treat patients in other markets who can travel for treatment. Providers in neighboring countries, such as Malaysia and Thailand, could be supported remotely from the regional headquarters through education or virtual visits from sales representatives.

8. Reorganize for effectiveness and scale

Companies looking to meet the unique needs of CGT patients, caregivers, and payers at scale will likely have to rethink their operating models for maximum efficiency. When commercializing CGT within a larger established business, companies can choose between several models. At one end of the spectrum, companies can create an independent CGT unit for all relevant commercial functions across all markets; at the other end, they can fully integrate the CGT business into the central footprint, with dedicated CGT resources within each function.

Merging capabilities

Larger pharmaceutical companies are increasingly acquiring new cell and gene therapy (CGT) companies. We recently helped a global pharmaceutical company evolve its operating model after it acquired a gene therapy company with multiple products in development. The combined company faced the challenge of building a commercial model that was tailored to the unique needs of gene therapy while also leveraging the existing scale of the parent organization and presenting a unified voice to external stakeholders, including payers and regulators.

We started by defining the capabilities required to support the successful commercialization of CGT. From this foundation, we collectively designed an operating model that considered three key factors:

• Structure . A combined global and in-market organizational structure clarified which functions should be dedicated to gene therapies, including patient access and account support, and which could be shared with the parent company, such as market insights.
• Responsibilities . This includes identifying and adjusting the responsibilities of key groups in the core gene therapy functions. Setting the price of new therapies, for example, required a clear division of roles between the global pricing team and the in-market pricing team of the parent company and of the CGT.
• Interfaces . Solutions were designed to overcome potential friction points—such as the need to protect the resources of CGT-dedicated teams that report into parent company teams, as well as how to facilitate knowledge sharing between CGT and non-CGT groups.

The result was an aligned, fit-for-purpose model that supported the delivery of unique gene therapy capabilities and made strategic use of the parent company’s existing commercial footprint.

Companies that have recently acquired CGT assets have chosen a variety of models depending on circumstances. Some prefer not to integrate the new CGT asset at all to avoid disrupting ongoing efforts to launch it. If integrating the new asset—given that specialized CGT therapies often need distinct capabilities—many prefer to keep specific commercial functions (such as patient engagement, site operations, and market access) independent. In almost all examples, the model evolves over time, and learnings from CGT launches are integrated into parent organizations (see sidebar “Merging capabilities”).

With so many new CGTs in the pipeline and poised for commercialization, the imperative to enable their benefits as widely as possible is as urgent as ever. Successful launches are key to maximizing the benefits of CGTs for patients, for healthcare providers, and for the companies that develop and distribute these life-changing therapies. Ensuring that the market, the product, and the company itself are fully prepared for an effective launch will enable success. The time to resolve the challenges of commercializing CGT therapies is now.

Simon Alfano and Alex Gorham are associate partners in McKinsey’s Boston office, Alberto Loche is an associate partner in the Zurich office, and Pablo Salazar is a partner in the Stamford office.

The authors wish to thank Emily Capra, Yingkun Hou, Eric Koskins, Nils Peters, Arnold Scaglione, Jeff Smith, Michelle Suhendra, Lieven Van der Veken, and Guang Yang for their contributions to this article.

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