The groundbreaking potential and record costs of recently launched cell and gene therapies have captured the attention of the entire healthcare ecosystem and the press alike.

Cell and gene therapies have revolutionized the lives for many patients suffering debilitating or life-threatening conditions, often offering the first potentially curative treatment option. Striking examples include Luxturna, which can restore sight in patients suffering from blindness caused by a rare genetic mutation-associated retinal dystrophy, and treatments for spinal muscular dystrophy (SMA).

However, these therapies come with high price tags, with seemingly every launch reaching a new record price for a therapeutic. In September 2022, Bluebird Bio’s cell therapy Skysona indicated for ALD was priced at $3 million per treatment in the US, placing it as the most expensive therapy in the world. This is nearly $1 million more expensive than Novartis’ gene therapy Zolgensma indicated for SMA, which previously was the most expensive therapy, at $2.1 million per treatment. It is worth noting, that for now all these therapies have targeted rare and ultra-rare conditions.

The recent advancements in cell and gene therapy development have been exponential, nonetheless, there is still a lot more to come. With more than 280 commercial assets currently in Phase II or III trials, many new approvals are expected by 2032. All stakeholders invested in the use of these therapies need to collectively address critical considerations to pave the way forward as the cell and gene market develops from a pioneering landscape into a fully mature market. As more medicines are launched, the number of patients eligible for treatment grow, into millions and current structures are not able to finance and deliver cell and gene therapies at this scale. It will be imperative for all health stakeholders to collaborate and build the right ecosystem to enable access and delivery of these treatments to the patients who will benefit from them.

CELL AND GENE THERAPIES (CGTX)

Cell and gene therapy is the introduction, removal, or change in the content of a person’s genetic code with the goal to treat or cure a disease. This is achieved by either directly injecting genetic material in their bodies or using modified cells and (re)inserting those as the therapy.

Breakthrough headlines on cell and gene therapies have been abundant in recent years. For example, most recently, the European Medicines Agency approval of Ebvallo from Atara Biotherapeutics for EBV PTLD marked the milestone for the first allogenic cell-based gene therapy receiving regulatory approval.

Since the first gene therapy launched in Europe in 2012, there have now been 15 launches of cell and gene therapies in the US and EU. The rate of launches has been rapidly increasing with over 50% of launches having occurred in the last two years alone.

The steady stream of new cell and gene therapy approvals have driven market growth at a 153% CAGR between 2017–2021. The US was critical for the CGTx market growth, particularly in the first years of therapy launches. The US market has paved the way, and now the European market is catching up. European growth is primarily driven by Zolgensma’s success in obtaining early reimbursement agreements on an outcomes-based basis. The increased number of European launches, such as Roctavian and Upstaza will contribute towards future growth in Europe.

CGTX TO DATE

The road towards marketing cell and gene therapies has been over 50 years in the making by the combination of scientific, clinical, and regulatory breakthroughs. The first scientific advancements towards cell and gene therapies were made between the 1960s and 1970s and the first in human clinical trials commenced in 1990. Eventually, Glybera was approved in 2012 marking the first gene therapy approval in Europe or the US.

After many years of progress working towards the first cell and gene therapy approval, new approvals are now a regular occurence. Until recently, there have only been a handful of therapies on the market. These few therapies have already caused payers, providers, patients, and the manufacturers to rethink their normal operations to effectively deliver these treatments to eligible patients.

There are over 500 cell and gene therapy commercial clinical trials globally which hope to expand cell and gene therapies into new therapeutic areas. The cell and gene therapy pipeline indicates that cell based immune oncology therapies will continue to dominate the space as they already do to date. Nonetheless there are also notable changes to be expected from the pipeline, including the expansion into additional therapeutic areas for example, beyond oncology and rare diseases, into neurology, metabolic diseases.

The anticipated cell and gene therapies in the pipeline will bring further challenges to the cell and gene therapy ecosystem, calling for new approaches from payers, providers and manufacturers.

FUTURE OF CGTX

Looking forward, we can anticipate two main challenges to the cell and gene therapy landscape, the higher number of therapies as mentioned above and the increased size of their indicated patient populations.

Cell and gene therapies are being developed and launched in larger patient populations, thereby migrating from ultra rare diseases into more common indications. By analyzing the sequence of launches to date and anticipated launch pipeline, one can observe a trend towards addressing broader patient populations, which is partially driven by the expansion into new therapeutic areas.

The first wave of historic cell and gene therapies launches, were targeted at ultra rare and rare diseases with incidences as low as one in 1,000,000, within rare haematological malignancies or uncommon inherited rare genetic diseases. With the launches of 2022 and those anticipated for 2023, cell and gene therapy indications will shift into much larger patient populations by targeting less rare diseases. For example, Roctavian for haemophilia A lies within an incidence rate of one in 10,000. This is a five to ten-fold increase in magnitude compared to the elligible patient populations served by gene therapies so far. Towards the end of the decade, cell and gene therapies could be targeting diseases as common as sickle cell disease and Parkinson’s disease.

The increased number of approved cell and gene and their expansion into larger indications with hundreds of thousands of patients instead of a few hundred will drive a rapid cumulative increase in the total addressable patient population. The theoretical total addressable patient population for all cell and gene therapies expected to launch in the US and Europe by 2028 will reach 1.6 million.

This rapid growth further emphasizes the need for readiness across all stakeholders to facilitate the successful adoption and use of cell and gene therapies.

HOW TO PREPARE

Ten years ago, the first gene therapy was approved in Europe. Since then, healthcare systems, manufacturers, and providers, have pioneered the use of cell and gene therapies in patients and continued to drive innovation. Looking ahead into the next ten years, we are beginning to enter an era where cell and gene therapies will become and established treatment modality. The launch of cell and gene therapies thus far, has highlighted numerous hurdles across stakeholders. Healthcare systems and the respective stakeholders will need to address various challenges along this journey. Mutual collaboration will be the key to developing a sustainable and effective cell and gene treatment ecosystem.