Clinical trials of a drug that could treat seizures in people with mitochondrial diseases are set to begin in the UK. We talked to Matthew Klein of PTC Therapeutics to find out more.
Hi Matthew, can you start by telling us a bit about PTC Therapeutics?
PTC is a global biopharmaceutical company, we have about 1300 employees and a footprint in over 50 countries. The company was founded almost 25 years ago, with a specific purpose to use innovative science to help identify new therapies for people with rare disorders. That remains our focus today. We have a very strong research organisation that discovers innovative therapies, and a development organisation that does clinical trials and studies, to allow these therapies to reach patients. We are proud to have successfully developed several therapies that are used by patients today.
What's your role at PTC?
I'm the Chief Operating Officer, overseeing a great deal of our activities across the company. I'm particularly close to the part of the company that develops drugs for approval worldwide, and personally I've been involved in developing therapies for patients with mitochondrial disease for well over a decade. I'm a physician by training. I had a career as a plastic surgeon for a number of years, focused on burn reconstruction, helping children and adults recover from serious injuries. I transitioned from that to the biotech industry, specifically to work in the field of mitochondrial disease.
What drew you to work in the field of mitochondrial disease?
I had my professional background in science and clinical trials, and a clinical career taking care of sick children. Working with mitochondrial disease was an opportunity to use all of these different experiences, as a physician and scientist, to help people who desperately need therapies. It's such an important field, and as I travelled around the world, meeting other physicians specialising in mitochondrial disease, I became increasingly drawn into it. When the opportunity came up to work full time developing these therapies with PTC, I jumped at the chance.
What's unique about mitochondrial disease, compared to working with other rare diseases?
Mitochondrial disease is incredibly complicated compared to other areas of disease. Really it's a family of diseases, and each member of that family is very different. When you look at the complexity of the genetics, it poses many challenges both in terms of caring for patients and in offering effective therapies. One of the most striking features is how badly we need therapies for those affected. It has to be a team effort, because it involves patients and their families, physicians, foundations, patient advocacy groups, scientists, and companies. This is a hard mountain to climb, and we'll only get there by working closely together.
How important is the role of charities like The Lily Foundation in new drug development?
It's incredibly important. We need strong partnerships with organisations like The Lily Foundation, which are really focused on the patient community, to help increase awareness about education about clinical trials. It's important to understand that the culture of clinical trials in mitochondrial disease is still in the early stages, because compared to other diseases there have been relatively few treatments developed. This is especially the case for children with mitochondrial disease. So it can be hard for parents and families to understand what a clinical trial is, why we need them, what they involve. For people without a medical background, there will be a lot of questions. So the partnership with Lily, which is incredibly respected in the global mitochondrial disease community, and does so much to provide information and support for families, is critically important.
Can you tell us a bit more about the clinical trial?
This is a worldwide trial, going by the name of Mit-E. It's aim is to study the efficacy of a drug for children and young adults up to 21 years of age, who have seizures as part of their mitochondrial disease. We know that almost half of patients with mitochondrial disease have seizures. Often these seizures are very severe, and don't respond to the usual medications. They can result in hospitalisation, and in the worst cases they can lead to infection and can be fatal. So there's a clear need for therapies to treat this aspect of mitochondrial disease.
The study will involve patients with a confirmed diagnosis of mitochondrial disease, who have a certain number of seizures and which are not responding to other medications. UK patients who enrol in the trial would go to one of our two study sites, in London and Newcastle. The teams there would evaluate them to see if they meet certain criteria in terms of age, disease, what medications they are taking, etc. If you meet those criteria, then you'll be invited to take part in the trial.
The first stage of the trial is a month-long period where we track the seizures. Participants are given a little device, similar to an iPad, so they can enter the data easily at home. Those who experience a minimum of six seizures in that period will be given either the drug we are trialling, or a placebo, for a six month period. Over that time we measure the number of seizures – again that's all done at home using the tablet device – to see if there's a difference between the two groups. Importantly, after that six months, all participants in the trial can get the study drug, so everyone has an opportunity to try it.
When and where is the trial happening?
This trial is open to enrolment now, at both our UK sites; Great Ormond Street Hospital in London, and the University of Newcastle. We're also conducting the trial at several study sites across Europe, US and Asia. We're looking to enrol 60 participants in total. We're hoping to have our first results by the end of this year, and then depending on those results we would meet with regulatory authorities and discuss next steps to move towards getting the drug available to patients.
Is it hard to recruit sufficient patient numbers for a trial of this sort?
It's challenging, because of the rarity of the disease. If we were doing a study into high blood pressure or diabetes, for example, you'd be looking at a potential patient pool of millions. But with a rare disease it's harder, particularly when you need patients of a certain age, with specific symptoms. In the case of this trial, we are looking for patients with the particular symptom of seizures, and this encompasses many different types of mitochondrial disease; MELAS, Alpers POLG, Leigh syndrome, MERRF. Basically if you have mitochondrial disease and seizures, you could be eligible.
We also understand that mitochondrial disease can be very challenging for those affected, physically and in terms arranging travel and care support, and that can impact their ability to take part. This is particularly important in the Covid pandemic, when travel has additional risks. For this reason, we've done our best to limit the number of hospital visits patients would need to make during the trial, including making it easy for them to track their own data at home.
We chose to go ahead with the trial despite the pandemic, even though we knew it would pose some challenges, because quite simply we knew that mitochondrial disease is not taking a 'time-out' for Covid. The need for effective treatments is so urgent, we didn't feel it was right to wait. There are challenges involved, but without the trials we won't be able to develop the therapies that could help these people, so you need to approach it the right way.
You've worked in mito research for many years. Do you feel positive about the advances being made?
Absolutely! When I started working in this area of research in 2008, the idea that there might one day be therapies for people with mitochondrial disease was a dream. There were no clinical trials going on, really no drugs in development at all, and not a lot of research focused in that area of medicine. Any research that was happening was limited to a few specialist centres. But over the past decade or so, there has been tremendous growth in research and enthusiasm. Patient groups, researchers, drugs companies and academic centres have come together in a more global collaboration. Generally we've seen a real acknowledgement that this is an important area of research, and that it's going to take multidisciplinary effort to make a difference. There's a lot of work still to be done, but I'm delighted to see all the progress being made.
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