Key Strategies for Advancing Gene and Cell Therapy Development

August 03, 2020 - Experts believe that the next generation of cell and gene therapies holds significant promise for patients because this alternative treatment option represents an advancement in personalized medicine.

It creates a point-of-care that may potentially cure many illnesses because each cell and gene therapy is designed based on detailed information about the roots of a patient’s disease. 

But despite their treatment promise, researchers face several challenges of gene and cell therapy development because the treatments require a different set of capabilities from the traditional pharmaceutical process. At the same time, patient demand for the innovative therapies are increasing.

Today’s drug development environment may be ill-equipped for this increase. 

In the following article, PharmaNewsIntelligence breaks down the fundamentals of cell and gene therapy, where the cell and gene therapy market is today, and how to combat the top challenges to foster gene and cell therapy development. 

READ MORE: Cell and Gene Therapy Development Increased 20%, PhRMA Finds

What are Cell and Gene Therapies? 

According to the British Society for Gene and Cell Therapy, cell therapy is the most recent phase of biotechnology in which scientists introduce new, healthy cells into a patient’s body to replace the diseased or missing ones. 

The human body contains well over 200 different types of specialized cell types total. These include muscle, bone, and brain cells.These cells are all responsible for different functions of the body. But injury or chronic disease can lead to the loss of these cells, and sometimes, the damage is irreversible.

Cell therapy helps by leveraging a patient’s own or a donor’s stem cells, which divide to form additional cells that contain a more specific function.

The difference between stem cell therapy and cell therapy is that during cell therapy, the collected cells are altered before being returned to the patient, unlike stem cell therapy.

READ MORE: First Gene Therapy Clinical Trial to Address Genetic Blindness

Researchers can better understand how diseases occur by watching stem cells mature into a cell therapy. 

Individuals who may benefit from cell therapy are those with chronic conditions such as spinal cord injuries, type 1 diabetes, Parkinson’s disease, amyotrophic lateral sclerosis, Alzheimer’s disease, heart disease, stroke, burns, cancer, and osteoarthritis.

Gene therapy is the introduction, removal, or change in the content of a person’s genetic code with the goal of treating or curing a disease.

If a mutated gene causes a vital protein to go missing, gene therapy can help to introduce a normal copy of the gene and restore the function of the protein.

The main difference between gene therapy and cell therapy is that gene therapy involves the transfer of genetic material into the appropriate cells of the body. Cell therapy is the transfer of cells with the relevant function into the patient.

READ MORE: FDA Aims to Bolster Gene Therapy Development with New Guidance

Some viruses are used as vectors because they deliver the new gene by infecting the cell. But the virus is modified before it can be used to carry therapeutic genes into the cells in order to remove the ability to cause an infectious disease.

“In gene therapy, scientists can do one of several things depending on the problem that is present. They can replace a gene that causes a medical problem with one that doesn’t, add genes to help the body to fight or treat disease, or turn off genes that are causing problems,” FDA said in  a release.

So far, at least 18 therapies have been FDA approved for certain types of chronic diseases.

The Current Role of Cell and Gene Therapy in Pharma 

The cell and gene therapy market has substantially increased over the past few years, with pharmaceutical companies partnering to create effective and accessible therapies for patients.

Currently, there are 362 cell and gene therapies in clinical development. This a 20 percent increase from 2018, PhRMA reported.

There are six diseases currently treated with gene or cell therapy for the treatment of cancer, eye diseases, and rare hereditary diseases.

Researchers also estimated that there were more than 1,000 cell and gene therapy clinical trials around the world by the end of 2019, including 352 gene therapies, 452 gene-modified and cell-based immuno-oncology (IO), 216 cell therapies, and 46 tissue engineering.

These trials focused on a range of modalities that targeted a variety of diseases across therapeutic areas. 

Pharmaceutical companies that specialized on cell and gene therapies raised nearly $2.6 billion in the third quarter of 2019. 

These funds have added up to a total of more than $7.4 billion going toward clinical trial research. Given the number of clinical trials in various stages, there may be more than 200 investigational new drug applications a year through 2025. 

Recently, Oregon Health & Science University (OHSU) held the first ever gene therapy clinical trial, BRILLIANCE, to address blindness-causing gene mutation, LCA10. 

The trial is one of 14 different clinical trials investigating new genetic treatments for ophthalmic conditions and nearly 50 vision-related clinical trials. 

“Being able to edit genes inside the human body is incredibly profound,” said Mark Pennesi, MD, PhD, the Kenneth C. Swan, associate professor of ophthalmology in the OHDU School of Medicine and chief of the OSHU Casey Eye Institute’s Paul H. Casey Ophthalmic Genetics Division.

“Beyond potentially offering treatment for a previously untreatable form of blindness, in vivo gene editing could also enable treatments for a much wider range of diseases,” added Pennesi, who leads OHSU’s involvement in the trial.

Last week, market and research company, Arizton, uncovered that the global cell and gene therapy market is expected to grow at a CAGR of over 30 percent during the period 2019−2025. 

Currently, The US is dominating the cell and gene therapy market with highest absolute growth of more than 500 percent and growing at a CAGR of around 36 percent, they said. 

FDA estimated it will approve up to 20 cell and gene therapy products a year by 2025.

How to Overcome Cell and Gene Therapy Challenges

Although cell and gene therapy has shown great promise thus far in the pharmaceutical sector, there are various challenges that could create roadblocks in the future.

Today’s drug development environment was largely designed around small molecules and biologics, such as proteins and monoclonal antibodies.

Therefore, FDA’s Competitive Generic Therapy (CGT) environment may be ill-equipped for the demand of therapies because cell and gene therapies require a different set of capabilities.

Experts stress that the pharmaceutical industry needs more capabilities to develop and commercialize CGT at scale while rethinking the end-to-end system.

A suggestion to combat this challenge from the Alliance of Regenerative Medicine is to turn to professional manufacturing organizations, both contract manufacturing organizations

and contract development and manufacturing organizations, to help develop and manage manufacturing programs. 

Startups and small therapeutic developers who may not have the necessary resources to properly manage and manufacture could benefit from outsourcing strategies.

Another pressing challenge is managing the clinical trial subject and patient experience throughout the cell and gene therapy treatment process because unlike traditional therapies, CGT requires increased patient engagement and support during a much longer treatment process.

And to complicate things further, most therapies receive either the FDA’s Regenerative Medicine Advanced Therapy Designation or breakthrough designations. 

This boosts small clinical trials and leads to a shortage of experienced physicians who are equipped to run CGT trials. 

So experts suggest that researchers scale operations to manage the increased patient engagement. 

“To deliver CGT therapies, treatment centers have to engage with clinical trial sponsors’ patient operations and services functions to shepherd patients through the treatment process,” researchers explained. 

Overall, cell and gene therapies have the potential to significantly transform healthcare systems and improve the lives of thousands of patients globally. Stakeholders must work together to combat potential challenges of manufacturing cell and gene therapies in order to improve patient access to and understand the significant potential of these medicines.