Economies of scale: Genetically-targeted therapies

Sarah Cook

15 September 2021


The genomics revolution has given us an exceptional understanding of what genes do, how they are expressed (turned on or off), and what happens when they don’t work as they should. These insights have paved the way for novel approaches to treatment that target genes themselves as opposed to their downstream products, proteins. 

Genetically-targeted therapies (GTTs) are drugs that work by either delivering healthy copies of genes to target cells, permanently changing the genetic code, or manipulating gene expression. Several GTTs are already approved for use in patients, and many more are being investigated in clinical trials. GTTs hold great promise for monogenic diseases (i.e. those caused by mutations in single genes) , in particular, where they present the opportunity to address the cause of the disease as opposed to just the symptoms.

In our latest briefing produced with support from the WYNG Foundation, we discuss the opportunities and technical challenges associated with one type of GTT, oligonucleotides. One of the major barriers to success of GTTs is their extremely high cost. So, why are they so expensive - and can anything be done about it?

Therapies for monogenic conditions

A major benefit of GTTs is their adaptability; they can be designed specifically for an individual. This is revolutionary for those with genetic diseases, as there is often no treatment available for their typically rare and sometimes unique conditions.

The technologies underpinning these therapies, including genome editing, gene replacement and oligonucleotide synthesis, have been a burgeoning area of research and innovation over the past few decades. Gene replacement therapy, as the name suggests, delivers a healthy copy of a gene to target cells, whilst genome editing enables permanent changes to be made to genes either to correct mutations or turn genes on or off. There are several types of oligonucleotide therapies, each utilising different mechanisms. However, oligonucleotide therapies all work by altering the expression of genes, either to correct the detrimental effect of a mutation or inhibit unwanted gene expression.

The cost of getting personal

There are several GTTs on the market, but their exceptionally high cost can prevent access to patients who could potentially benefit from them – especially for people without comprehensive health insurance coverage or in public health systems with limited resources such as the UK NHS (National Health Service).

For example, one of the most well-known oligonucleotide therapies is a drug called Spinraza, for children with spinal muscular atrophy. Spinraza is an oligonucleotide therapy that works by enabling cells to produce a healthy version of the survival motor neuron (SMN) protein that these patients lack. It is incredibly effective, but it costs around £66,000 per dose, with several doses needed per year. Another drug for spinal muscular atrophy, Zolgensma, is often described as the most expensive drug in the world. This gene replacement therapy works by delivering a healthy copy of the SMN gene to cells, and costs £1.79 million for a single, one-time dose.

These particular treatments are available through the NHS, as they have been shown to be highly effective in treating life threatening disease, therefore providing enough benefit to justify their high costs. However, other GTTs such as Libmeldy, a gene therapy for children with metachromatic leukodystrophy, have not been found to meet cost-effectiveness thresholds for use, despite evidence showing that it ameliorates disease progression.  

Looking more broadly, insufficient commercial incentive (ie. prospects of financial return on costs) will often mean that potential GTTs may never go into development in the first place. The price of a new treatment is dependent on many factors, most notably the costs of research and development, manufacturing and processing; the health value it offers, in terms of increased quality and quantity of life; and the size of the patient population that could benefit from it.

R&D costs are generally very high, especially as companies have to cover the costs of research into a much larger number of treatments than will ever successfully reach the market. In the case of rare genetic diseases, the patient population for any one condition is small, often comprising only one or a handful of individuals that have a specific mutation. Without sufficient commercial incentive to develop treatments for individuals with ultra-rare diseases, these patients are faced with the reality that although a GTT could theoretically help them, it won’t be developed unless they are able to raise the funds themselves.

Are platform technologies the answer?

Each new GTT is developed to address either a specific disease or a specific gene, and each one will use a slightly different method to deliver the drug to its target. There will also be differences in the way each GTT is manufactured. All these differences require their own, substantial, preclinical testing to determine their safety and whether they will reach the right tissues and cells within the body.

However, as more GTTs are being approved, possibilities for streamlining development and scaling up production is emerging.

One exciting prospect, albeit in the earliest stages of research, could be the creation of ‘platform technologies’ where the core safety profiles, pharmacology, bio-distribution and metabolism of the therapy are all known and approved for use. All that would vary would be the content unique to each therapy i.e. the genetic material delivered and/or the tools required to target specific genes, much as the functional heads on a multi–tool might be changed depending on the job in hand.

Platform technologies could drastically reduce the amount of preclinical testing required to bring a new drug to market, as only the modifications made to each platform would have to be evaluated. This would reduce the cost of GTTs whilst expanding the number of potential patients who would benefit.

Progress towards patient benefit

Bringing this attractive vision to reality will require a range of developments, but several organisations and pharmaceutical companies are working towards delivery of GTTs for patients. For example, the UK’s Cell and Gene Therapy Catapult has several activities relating to the scaling up of production and manufacturing of GTTs. In addition, the National Center for Advancing Translational Sciences in the US is working with the FDA to investigate how the regulatory environment can be evolved to accommodate platform technologies.

This is an exciting time for novel and innovative therapies in terms of both scientific capabilities and the enthusiasm of policy makers and health professionals. However, even beyond issues of cost effectiveness, ensuring the regulatory environment is also amenable to these advances whilst guaranteeing the safety of patients will be a major challenge. As explored in our oligonucleotide therapy briefing, the potential of these types of therapies for rare genetic diseases is phenomenal - and their impact for patients could go far beyond these diseases to many other conditions.

Read more about the broad range of potential diseases that could be treated by oligonucleotide therapies here.


Genomics and policy news

Sign up