The RDCE focuses on advancements in rare disease clinical trials. From innovation to patient recruitment, Zizi and her PAREXEL colleagues hope to change the landscape of rare disease studies and bring medicines to the patients who need them in a faster, more cost-efficient way.
“There are more than 7000 rare diseases in the world, one in 20 people will live with a rare disease at some point in their lives and it’s crucial that we raise awareness,” says Zizi, adding: “One of the biggest challenges with dealing with rare diseases is that we only have a very small patient population. Compounding that is the fact that when you’re trying to investigate these conditions, most of the patients who have rare diseases are often misdiagnosed.”
The reason this happens, she explains, is because rare diseases constitute a complex set of ailments that involve a wide range of specialist disciplines. The average rare disease patient is usually misdiagnosed at least two or three times, can see up to seven specialists and may have to wait up to seven years to get properly diagnosed. PAREXEL has participated in more than 240 rare disease projects during the past five years at more than 3700 sites with in excess of 16,000 enrolled patients.
“It’s crucial to understand the challenges that face rare diseases and the huge areas in which innovation can really help,” says Zizi. “One of the key hurdles that needs to be overcome is patient recruitment. Because we’re dealing with rare diseases, patients are scattered far and wide, and dispersed throughout many different countries, regions and states."
"So, we are developing more innovative ways to bring the clinical trial closer to the patient, such as video dosing so that patients can be treated without being in the clinic — having previously seen a physician — either by sending nurses to their homes or by using telemedicine. In this way, patients can talk about their condition/illness, and also their progress, with a doctor.”
She continues: “We’re also implementing the use of sensors, wearable devices, etc., because one of the main issues involved in treating rare diseases is the endpoint or outcome. Often, the patient perspective can be quite different from the physician’s point of view in terms of clinical significance. It’s critical that you have outcomes that are actually beneficial to the patient. So, having good sensors, for example, is a good way to monitor and detect these kinds of endpoints.”
The data dilemma
I mention to Zizi that we hear more and more about the amount of data that’s collected from patients, etc., but question whether this accumulation of information is actually helping with the diagnosis and treatment of rare diseases. “It’s interesting that you say that,” she says: “I’ve just returned from a conference on orphan drugs in London and it’s one of the things we talked about.”
“One of the difficulties with data,” she explains, “is that, yes, we have it … but most of that data doesn’t talk to each other or it’s owned by different people. With rare diseases, it’s very helpful to understand the patient journey or the natural history of the patient, whereby you can track the background of the individual, from when they’re born, how they live their life, when they become affected by a disease, when they’re cured … or die … and so on. Most of the data pertaining to all these diverse aspects resides in different places (laboratories, electronic health records, etc.).”
Despite the historical data silo mentality, though, a number of companies are now using techniques such as artificial intelligence (AI) to mine and analyse this data to make it more meaningful and helpful. “Another good source of data is pharmaceutical companies,” adds Zizi: “Many times, when we do studies and those trials fail, the data is not made available; this is slowly changing and there is a push within the industry to gain access to what sometimes amounts to years of collected statistics.”
The money question
Asked whether treating rare diseases is a third-world or funding problem, Zizi acknowledges that the cost of therapy for rare diseases in both developing and developed geographies is very expensive. “It touches on issues of market access,” she says: “For example, pharmaceutical companies often conduct clinical studies in countries where they’re not actually planning to sell the drug. They just wouldn’t be able to generate enough return on their investment.”
“But, at the same time, they are starting to create greater access and more availability to those compounds, especially if they’re working in regions for compassionate or humanitarian reasons where it would be difficult — if not impossible — for the local healthcare infrastructure to afford the drug.”
I suggest that developments in technologies such as continuous processing are enabling the cost-effective production of smaller batches and more personalised therapeutics, which could offer financial benefits. “It could well be a positive move, depending on the type of compound being made,” notes Zizi. “When you talk about cell and gene therapies, those present a different array of challenges … and are already made in small batches. For chemical entities, though, any development that makes the manufacturing process cheaper, more efficient or more reactive has got to be an advantage, especially if some of those cost savings are passed on to the patient.”
Looking to the future
Unlike many of today’s prevalent maladies, very few rare diseases fall into the lifestyle category. “Of course, diet, stress, exercise and smoking are all significant factors in overall health and well-being, but the basis of most rare disease is genetic. Epigenetic factors probably play a greater role,” says Zizi. She goes on to make the point that better collaboration is key.
“At the heart of it, there needs to be a closer relationship with the sponsor pharmaceutical company and the patient. Physicians are looking for certain endpoints, as I mentioned, such as being able to take a specific number of steps to assess the efficacy of, for example, a muscular dystrophy drug. But that might not correlate with the patient’s definition of a cure; they might say that they just want to be able to lift something or get up out of a chair.”
Getting the patient perspective is critical, including what’s important to them and what makes sense to them.
“Pharma companies also need to establish better relationships, earlier, with the regulatory bodies in the EU and US, for example; these agencies are very open to working with rare diseases and we, as an industry, have been able to expedite the progression of new therapies into the market by taking a more proactive approach to talking with the FDA. If you look at all the drugs that have been approved during the last two years, you’ll see that more than 40% have orphan designation, which is very positive. We’re clearly moving in the right direction,” she adds.
With a magic wand for the day, Zizi would fast-track the implementation of AI technology to improve and accelerate the identification of rare disease patients — not just for the sponsor companies, but also to generate more open-access data. “The quicker we can find the patients who need to be included in these studies, the better we will be and the quicker we can eliminate these rare diseases.”
“The thing with rare diseases,” concludes Zizi, “is that there’s a community aspect. Stakeholders such as pharmaceutical companies and biopharmaceutical service providers such as us need to operate, collaboratively, within that community to better understand the patient journey, recognise what’s meaningful to them and their caregivers and, ultimately, revolutionise the way rare disease studies are supported and managed.”
NB: This article will appear in the April 2019 issue of Manufacturing Chemist. A recent digital edition is available online.