Cell, Gene Therapies Are Expected to Rapidly Expand

Pharmacy Practice in Focus: OncologyFebruary 2021
Volume 3
Issue 1

The classes of approved cell and gene therapies are expected to expand rapidly in the next few years based on projections in the field.

In the current landscape of approved cell and gene therapies, not many classes of products are available in the United States, said Rebecca Bigler, PhD, the chief scientific officer at Therapeutic Genetics Consulting Associates in Chapel Hill, North Carolina, during the National Association of Specialty Pharmacy 2020 Annual Meeting & Expo Virtual Experience. However, Bigler said during a session on the state of care for cell and gene therapies that the classes of approved products are expected to expand rapidly in the next few years based on projections in the field.

Currently, a small group of products span the classes of gene therapy and cell therapy, Bigler said. This small quantity is due to the generally poorly defined and poorly differentiated nature of these classes of products.

One method of managing this issue within the field is by classifying the products that span both gene therapy and cell therapy to be cell therapies in terms of their manufacturing, distribution, administration, and safety. Bigler said that this is the approach that Therapeutic Genetics Consulting Associates has taken to clarify the classification process.

Currently, Bigler said, cell therapy can be defined as the transfer of live human cells that have been manipulated during the manufacturing process to enhance their therapeutic potential. Products that practitioners in the field are commonly aware of that fall under this definition include brexucabtagene autoleucel (Tecartus; Kite Pharma) and tisagenlecleucel (Kymriah; Novartis).

Gene therapy, however, can be defined as the therapeutic manipulation of the DNA content of patients' cells that does not remove the cells in the process. The manipulation of the cells for this purpose is designed to implement persistent change in gene expression to treat or cure a medical condition. Products under this classification include voretigene neparvovec-rzyl (Luxturna; Spark Therapeutics) and onasemnogene abeparvovec-xioi (Zolgensma; AveXis).

There is also a third class of products that falls outside cell therapy or gene therapy that’s known as oligonucleotide therapy. This therapy is defined as drugs that harness naturally occurring cellular mechanisms to transiently modify gene expression, without changing DNA, to treat a medical condition. Common products used in the field under this classification include nusinersen (Spinraza; Biogen) and patisiran (Onpattro; Alnylam Pharmaceuticals).

The therapeutic focus within each category is very different, Bigler said. The product pipeline using these therapies addresses rare tumors versus rare diseases quite differently. In general, cell therapies are predominantly being developed for rare tumors, and gene therapy and oligonucleotide therapies are predominantly being developed for rare diseases and other diseases that fall under the specialty patient category.

“The lists of what’s in development are quite long,” she said. “There are over 400 gene and cell therapies under development, and that doesn’t even take into account the oligonucleotide therapies.” When it comes to gene therapy, quite a few diseases are amenable to this type of treatment, Bigler noted.

“Some of the considerations for these types of therapies include how it is administered. Some of them can be administered systemically [intravenously]; some of them, especially the neurological gene therapies, need to be administered through very special brain surgeries,” she said. “The recurrent high-grade gliomas are also administered through surgery to remove the large portion of the tumor, and then the gene therapy is administered to get anything that is remaining.”

Although only 3 gene therapy products are currently available, Bigler said they were each approved by the FDA with small amounts of data, short follow-up times, and modest patient numbers. However, it appears the FDA may be changing how it evaluates gene therapies.

“In August, there was a gene therapy for hemophilia A that was due for review, but the FDA decided to hold off reviewing it until the sponsor could provide 2-year data on all of the patients currently in the phase 3 trial,” Bigler said. “This delays the FDA’s decision by about a year and a half. Although there are a lot of predictions that this field is going to grow very rapidly, if the FDA decides to require more data and longer-term data, that is going to push back when this growth spurt is going to happen within the gene therapy pipeline.”

Among cell therapies under development, the vast majority fall under the category of treating B-cell malignancies, which are T-cell therapies. Currently, about 85% to 90% of the cell therapies are being developed to address these B-cell malignancy blood cancers, according to Bigler. However, the general therapeutic modality can be diverse and can address quite a few different diseases.

The oligonucleotide therapy is also quite diverse in the types of diseases it can address, including multiple tissues, the liver, blood, and the brain.

“One of the major limiting factors here is being able to administer the oligonucleotides to the correct cells in order to address the path of physiology of the disease,” Bigler said. “But one exciting feature of oligonucleotide therapies is under the rare tumor category. One group is developing these therapies for STAT3-positive hematological and solid tumors, so this would be tumor-agnostic therapy, based on the way these products work. The genetics of the tumor is more important than the tissue of origin. And that can be a great development in oncology, having these tumor-agnostic therapies for patients.”

Currently, the role of specialty pharmacy within these different therapeutic modalities is quite different, Bigler noted. Because gene therapies are being developed as a one-time treatment for patients with rare diseases—and because they are very expensive—they are not the type of drugs stocked at a specialty pharmacy. For this reason, special distribution models have been developed to allow for real-time dispensing to patients so they can receive these specialty medications as rapidly as possible.

There are generally 2 models followed by specialty pharmacies. The real-time dispensing model is used for some products. A majority of cell therapy products, however, are delivered directly to the location where they will be administered. Bigler said this distribution method is ideal considering the way the treatments are manufactured, which doesn’t fit well into the real-time dispensing model.

She noted that the dispensing of oligonucleotide therapies follows a more traditional specialty pharmacy distribution model, which requires considerations for stocking, shipping, inventory management, and patient engagement.


Bigler R, Calla N. State of care 2020: cell & gene therapy. Presented at: NASP 2020 Annual Meeting & Expo Virtual Experience; September 15, 2020. Accessed October 7, 2020. https://nasp.6connex.com/event/VirtualExperience/en-us#!/Lobby

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