A Not So Rare Problem

There are multiple pathways to overcome gene therapy manufacturing challenges at the small scale. But a solution that addresses the production bottleneck for the whole field – unlocking therapies for dozens of diseases, each encompassing tens of thousands of patients – remains elusive.

Gene therapies were initially developed to find treatments for patients with “rare” diseases and few (or no) treatment options available.  It’s still a struggle in the field to appreciate the scope of the challenges ahead as this therapeutic approach moves from rare to not-so-rare patient populations. We often get asked “what does rare really mean?” When you consider these five observations, you’ll realize that rare is not so rare after all (1):

• Today, there are thought to be over 7000 distinct rare diseases – and this figure is likely an underestimation.
• Globally, 400 million people are affected by rare diseases (there are 30 million people in the US alone – that’s one in ten of the total population).
•  Rare diseases impact more people than cancer and AIDS combined.
• About 50 percent of people affected by rare diseases are children.
• Over 80 percent of rare diseases have identified genetic origins.

That’s a lot of patients to develop and manufacture treatments for! Clearly, there are many people – hundreds of millions around the world – who might benefit from access to gene therapies. Yet treatments remain woefully underdeveloped; in the US, over 90 percent of all rare diseases do not have a single FDA-approved treatment.

The first step is to forget about the concept of rarity, instead focusing on removing obstacles so that all patients with genetic diseases receive attention. Enabling access to therapies to the greatest extent possible can be a resource problem – particularly when we consider the scope and scale of manufacturing. Right now, it takes a great deal of time and effort to develop, scale, and manufacture a gene therapy.

Let’s work through an example: one 1000 L bioreactor can produce sufficient material to treat 10–20 patients using the most common form of gene therapy. From start to finish, it can take 6–12 months and millions of dollars to manufacture one 1000 L lot of drugs in a bioreactor. If we consider the 7000 different rare diseases known today, and the 400 million people globally who need treatment, we can quickly see how demand so easily overwhelms current manufacturing capabilities.

Compounded by demanding analytical and quality specifications, the obstacles to manufacture drugs for just one clinical trial can make it hard for companies to focus on a single gene therapy, let alone develop a pipeline for multiple rare diseases. Manufacturing is highly capital intensive, requiring specialized buildings, rooms, and equipment. And, on top of that, the pool of talent and expertise in current gene therapy “good manufacturing practices” is limited. It’s fair to say that supply–demand mismatches are significant across the entire industry.

Despite all these issues, we have seen successes in gene therapy. There are many novel drug candidates in the preclinical stage, and many others in clinical trials – each one offering hope for patients who may have no other option. But what good are they if there is nowhere to produce them in a timeframe that makes sense, given that time is the enemy for patients?

Scientists and doctors worldwide are working on solutions for millions of patients who need new treatments, and companies need innovative manufacturing solutions to bring their therapies to market. Let’s turn their hope into reality by enabling the solutions we know exist.