Precision gene therapy tools provide new hope for rare diseases

The market for orphan drugs is expected to reach $262bn (€233.4bn) by 2024, according to a report​ from EvaluatePharma.

With companies like Centogene expanding its global diagnostic capabilities, research data and natural histories have become more accessible – enabling drug discovery and development for rare diseases to become part of the global market.

Companies like Alexion demonstrate the growth capabilities of orphan drugs with Soliris ​(eculizumab) a monoclonal antibody (mAb) for rare disease atypical hemolytic uremic syndrome (aHUS) which utilizes genome sequencing technology for development. 

BioPharma-Reporter (BPR​) spoke with Oved Amitay (OA​), chief business officer at Centogene, on the impact of the technology like CRISPR/Cas9 on the drug development, along with the ways in which the market for rare disease drug discovery has expanded globally.

BPR: What are some of the ways in which the global market for rare disease drug development is growing?​

OA: ​The main reason that rare diseases became interesting from a drug development perspective is because they are genetically based, you have a very specific place to start your development program, really focusing on the genetic component.

If you think about more frequent diseases, they’re typically more complex like diabetes or hypertension. These diseases tend to have multiple causes and, of course, multiple genetic factors that come into play.

In the rare genetic diseases situation, very often we’ll talk about monogenetic diseases – where there’s a single gene that’s mutated or defective.

From a drug development perspective, having a single place to focus on is so valuable because then you have a much higher likelihood of addressing the underlying reasons for the diseases.

It’s basically because you know what to work on and what to look for and now there are more advanced tools that we can use to address that.

BPR: What are some trends in the rare disease drug discovery and development area?​

OA: ​In the past 10 years, and even more so in the past five years, the tools to address specific genetic changes, which now include CRISPR/Cas9, and the ability to edit DNA, now allow us to insert specific things to correct genetic information using specific tools of gene therapy, like viral vectors, are much more precise than 10 years ago.

The increasing number of therapies that are in development is really a reflection of those tools, and how they really open up the ability to address the diseases that, in the past, we could never really address.

BPR: What are some ways these gene therapies have become more accessible?​

OA: ​Because of the focus of rare disease drug therapy is on the specific genes that are affected, the ability to target them is more applicable because these needs are limited and are often separated from the entire body.

When you use advanced tools in gene therapy, you create value from a global market perspective at what you're able to create.

BPR: With something like a rare disease or ultra-rare disease, where you have limited amounts of clinical research, how does that impact the way in which drug development can occur?​

OA: ​By definition, they’re rare diseases so there’s a limited number of patients. Part of the issue is that some of the patients are misdiagnosed, or that they were given a different label, and then you also have patients who are not diagnosed at all. Perhaps, they have a form of blindness, but no one was looking at the genetic level towards their condition.

Part of the challenge behind even putting together a clinical program is understanding where the patients are. That’s part of the challenge, it’s a big need to understand where those patients are.

BPR: Why is it important to think of drug development for rare diseases globally?​

OA: ​Very often people focus primarily on the US, Europe, and Japan as the major markets for pharmaceuticals – for rare diseases, it’s the entire world.

Frankly, if you have a transformative therapy where you can get someone to walk or see again, you can’t just think about the patients in the US, you have to think about it globally.

You can’t just think about it for the patients in the US, because parents in India or China are just as desperate as the parents in the US.

Rare disease study and drug discovery tend to be more global in nature, with that though, you need to also be able to diagnose properly.

Oved Amitay currently serves as chief business officer at Centogene. Previously, he held the role as the head of commercial at Alnylam and general manager at Genzyme. He began his career in drug development with Peptor.​​