Handling New Therapies Moving Through Drug Development at a Rapid Pace

Drug development is inherently costly and time-intensive, with potential attrition a persistent burden on companies’ finances (1). As companies gain a deeper understanding of cell and molecular biology and seek to develop more complex therapeutics for patient populations, they will also need to be more innovative to ensure commercially viable success is achieved (2).

An area that has witnessed significant breakthroughs over recent years has been that of cell and gene therapies. The market for these emerging therapies is projected to grow at a compound annual rate of 22.41% between 2022 and 2030 (3), driven by an expanding pipeline and increasing regulatory approvals.

Despite the successes that have already been achieved with emerging therapy development and manufacturing, companies are still facing numerous challenges. Aspects such as demand for accelerated development timelines, advancing technologies, and the growing issue surrounding sustainability are monopolizing the priorities of bio/pharma companies. However, through new opportunities, like allogeneic cell therapy, it is hoped that greater benefits to patients, particularly those in undertreated populations, will be achieved (4).

In speaking with Anis H. Khimani, PhD, senior strategy leader, Life Sciences Strategy Group at Revvity, Pharmaceutical Technology® discussed with how new therapies are moving from their academic origins into industry.

Continued investment in cell and gene therapies

PharmTech: Is there anything specific you are seeing in terms of new emerging therapy development or manufacturing in the industry as of now?

Khimani (Revvity): Cell and gene therapies are delivering on the promise of curing diseases.Initially starting with CAR-T [chimeric antigen receptor T cells] treatments for hematological malignancies, therapies are now in the clinic for rare inherited genetic disease, infectious diseases, and solid tumors. Each of these therapeutic areas brings with it new technical and clinical challenges. From accurately targeting the diseased tissue, to ensuring that the corrected gene is expressing proteins at sufficient level to resolve the clinical symptoms, to ensuring that the products are robust, affordable, scalable, and accessible.

The more recent introduction of base editing offers the promise of more complex multiplexed editing with reduced off target editing and significantly lower indels and translocations. This approach is expected to reduce the time required to create therapies because editing can be performed concurrently instead of needing to be performed sequentially. Multiplex base editing has also been shown to have no impact on cell viability, so the yields will be unaffected. One example of base editing, the Pin-point™ system, has been demonstrated as able to knock-out immunogenic proteins and knock-in a targeted CAR within the same editing reaction, creating an effective functional CAR-T cell line with tumor-killing activity.

Addressing new short- and long-term challenges

PharmTech: Are there any new challenges or hurdles in the cell therapy space that should be addressed for the short- and long-term?

Khimani (Revvity): The production of cell therapies rely on accurate and safe editing without compromising the health of the cells being edited. To achieve this, there needs to be tight controls over cell isolation, editing, expansion, analysis, and delivery to the patient. The increasing number of processes being developed to address the cell therapy market will need to be consolidated at some point to create a standardized, scalable therapeutic approach. This will help to reduce manufacturing times and costs of treatment, and also create a framework for clinical trials and subsequent regulatory approvals, getting treatments to patients faster.

The benefits of utilizing allogeneic cell therapies

PharmTech: Why are companies starting to look at allogeneic cell therapies more closely?

Khimani (Revvity): Allogeneic therapies follow the traditional drug manufacturing process more closely than autologous cell therapies. The therapy can be scaled up so that the same product can be used to treat multiple patients, standardizing the product and reducing the cost per patient treated. As the tools used for gene editing to create allogeneic cell therapies continue to evolve and become more robust, it is imaginable that there will be an increasing interest and eventual preference for allogeneic cell therapies over autologous cell therapies.

Industry players and allogeneic therapies

PharmTech: Are allogeneic cell therapies a bigger opportunity for industry players, such as contract development and manufacturing organizations (CDMOs) and contract research organizations (CROs), and why?

Khimani (Revvity): Decentralizing manufacturing processes provides an opportunity for CDMOs and CROs to integrate into product pipelines. These industry players are already contributing their own expertise to accelerate allogeneic cell therapies, such as developing new analytical methods. As the cell therapy market continues to mature and CDMOs and CROs manage an increasing number of projects related to the development of this new generation of therapies, they will also mature their expertise, systems, and processes and grow their presence with the cell therapeutics industry. Cell therapies are rapidly evolving and are being developed to treat a broad array of disorders, so it is foreseeable that companies within the market will differentiate into having deeper expertise in a smaller number of specific therapies and/or areas of expertise over time.

Other up-and-coming therapy developments

PharmTech: What do you hope to see for the future of allogeneic cell therapies/any other emerging therapy development or manufacturing?

Khimani (Revvity): We hope that the combined learnings of this emerging and rapidly expanding class of therapies will see the acceleration of treatments and possibly cures for many devastating diseases. The first autologous cell therapy was approved in 2016, the first autologous CAR-T therapy was approved in 2017 and the first allogeneic stem cell therapy was approved in 2011, so we’re still at the starting line. Most promising, the development to approval timelines for cell therapies are trending faster than conventional therapeutics and the FDA has established a new, specialized office to process the increasing number of regulatory submission for cell and gene therapies.The current clinical trials address a broad range of conditions, including hematological malignancies, solid tumors, ocular conditions, infectious disease, autoimmune conditions, long COVID, inherited genetic diseases such as spinal muscular atrophy (SMA), severe combined immunodeficiency (SCID), neurological diseases including Parkinson Disease, depression, and diabetes. The breadth of indications continues to expand as we learn more about how to produce and administer cell and gene therapies, so it is an exciting era of medicine to be a part of.

References

• Agrawal, G.; Keane H.; Prabhakaran, M.; Steinmann, M. The Pursuit of Excellence in New-Drug Development. McKinsey & Company, Nov. 1, 2019. https://www.mckinsey.com/industries/life-sciences/our-insights/the-pursuit-of-excellence-in-new-drug-development
• McKinsey & Company. How AI Can Accelerate R&D for Cell and Gene Therapies. www.mckinsey.com, Nov. 16, 2022. https://www.mckinsey.com/industries/life-sciences/our-insights/how-ai-can-accelerate-r-and-d-for-cell-and-gene-therapies
• Precedence Research. Cell and Gene Therapy Market (by Therapy Type: Cell Therapy and Gene Therapy; by Indication: Cardiovascular Disease, Cancer, Genetic Disorders, Infectious Diseases, Neurological Disorders; by Delivery Method: In-Vivo and Ex-vivo; by End-Users: Hospitals, Cancer Care Centers, Wound Care Centers, Others)—Global Industry Analysis, Size, Share, Growth, Trends, Regional Outlook, and Forecast 2022–2030. Market Report, November 2022.
• Fontanillo, M.; Paulick, K.; Poda, P.; Silberzahn, T. Out of the Shadows: A Brighter Future for Pharma Technical Development. McKinsey & Company, Sept. 16, 2022. https://www.mckinsey.com/industries/life-sciences/our-insights/out-of-the-shadows-a-brighter-future-for-pharma-technical-development.