Published on 19/09/2022
The push for personalized medicine has been a key driver in drug development for years. However, providing the right treatment for the right patient at the right time needs to be based on a thorough understanding of patient profiles first, and tailoring treatments for them requires more precise diagnostics.
This is where digital tools come in, as they hold the promise of providing a more holistic view of a patient’s condition given their ability to merge metabolic, genomic and physiologic parameters – all of which can be collected with innovative devices. Based on this data, doctors and patients can potentially generate a more precise health picture. At least, that is the common goal of many scientists and physicians around the world.
Personalized medicine is also a key topic for the Innovative Medicines Initiative (IMI) of the European Union, which has launched almost 200 projects since 2008. As the world’s largest public-private partnership, the IMI provides over 5 billion euros in funding for health research and innovation, a budget which is jointly raised by the European Union and the European pharmaceutical industry.
One of these IMI projects is called Mobilise-D. It puts the focus on measuring mobility accurately so as to get the world at least one step closer to personalized treatments. Under the umbrella of Mobilise-D, a consortium of 34 partners – 22 public institutions, 2 tech and 10 pharma companies, including Novartis – aims to connect digital mobility assessment to clinical outcomes for regulatory and clinical endorsement.
At the Novartis Institutes for BioMedical Research, Ronenn Roubenoff and Tilo Hache are focused on the discovery of new diagnostic tools and treatment options for patients. Both play a leading role in the Mobilise-D project.
Going digital
“We started the Mobilise-D project on April 1, 2019. It has been running for three years now and is officially set to end on March 31, 2024,” says Roubenoff. “Novartis got interested in public-private partnerships through our needs in musculoskeletal disease to have better endpoints for trials, especially as the focus of my whole group is around mobility and how to measure it properly.”
The endpoints that the Mobilise-D consortium is looking for are outcomes or events in a clinical trial used to objectively measure the effect of an intervention being studied. Key endpoints in this project are the improvement of mobility and the quality of life.
According to Hache, data generated by wearable devices, such as a wristband recording acceleration or steps, can be a major factor to demonstrate that a drug is beneficial to the patient. More accurate assessments are now feasible in a way which is more convenient to the patient than maybe 10 years ago. “The technical evolution allows us to actually measure not only in the clinic – which we’ve been doing for decades – but also what patients do at home, in the ‘real world,’” says Hache.
People’s mobility is measured at the waist, the center of the body, for highest accuracy. The Mobilise-D project uses a device worn at the lower back to determine how people are walking. Many questions can be answered by this measurement – not only how many steps per day people are taking, but also how steady they are. Are patients walking faster or more slowly? How variable are their steps?
“We study mobility in four indications chosen for the project: Parkinson’s disease, COPD, multiple sclerosis and hip fracture. Data from these patients, and from healthy volunteers, is being collected to generate the Body of Evidence for a submission to Health Authorities for a qualification opinion,” says Hache.
“A lot of detailed data is still needed,” as Roubenoff says, “because we really don’t know yet, for any given disease, what is the most important feature of how patients walk, which will tell us whether they are doing better or worse. And that’s what we’re learning in the first part of Mobilise-D.” This phase is scheduled from 2019 to 2022.
Large clinical studies
In the second part of the project all of these endpoints will help to define clinical results, such as whether people are doing better in their specific disease, whether they have had falls or been to the hospital, and whether they have needed nursing home care, passed away or survived.
However, the clinical validation for the second part of the project is quite large with 600 patients in each indication and 2400 patients overall. As of April 2022, a couple of test centers have already completed the recruitment of patients for the trial. By comparison, the number of patients involved in the technical validation study was quite small with 100 patients and 20 healthy volunteers.
Finally, there will be an analysis segment to try and understand what is the best variable to measure, and whether the same variable applies across all the diseases – which would be nice, adds Roubenoff with a smile. “Otherwise we need disease-specific analyses. And if so, we’d better understand that sooner rather than later.”
Ten years of research
Novartis entered the area of measuring mobility back in 2012, a long time before the Mobilise-D project started, and is now exploring the fourth generation of technology used in Novartis trials. Looking back on all these years, Roubenoff says: “The hurdle for us was less the technological one about which device to use and how to do it. The real issue was what we would have to do to make it useful for drug development, to make sure that regulators have sufficient information from this to be willing to consider it as a primary or secondary endpoint in a trial.”
To provide this kind of information, the Mobilise-D consortium still has to link their digital measurement results to hard medical outcomes like death, hospitalization and falls. “In all of these disease indications, we have to demonstrate the validity of our new mobility outcomes during a specific period of time. It takes years of follow-up with patients, since Parkinson’s patients, for example, don’t fall every day, fortunately, and COPD patients likewise don’t suffer an exacerbation every day – to give just two illustrative examples. For correlating mobility to such ‘anchor’ endpoints, we have to capture probably one to two years of data in follow-up assessments,” says Hache.
One big advantage of the digital mobility measuring methods over the standard walking test at hospital which, for example, just measures the distance a patient can walk within six minutes, would be the ability to do the measuring at home – in the “real world.” “We are still working on this,” says Roubenoff. “To show that there’s a way to actually change the patient’s condition with a medicine is another challenge for us. And on top of that we need to show that a change in mobility could potentially reduce real medical outcomes like hospitalization, a fall, or a broken hip, or death. These are big long-term efforts. Even the duration of five years won’t be enough to complete all the work for this project.”
However, Hache takes the view that current efforts in the Mobilise-D project will be sufficient to achieve the project objectives, despite challenges from the COVID pandemic. “But post-project, we will have to build on the qualification advice already received from the health authorities, and further intensify our engagement with the FDA, the EMA and other regulators,” he adds. “There are enough challenges remaining even after the five project years are completed.”
Benefits of collaboration
Like any other pharmaceutical company, Novartis could not do all this work alone. There is no simple way to justify a financial investment in such a project when a company does not yet know if the new measurement is going to work in combination with a new drug. This is why public-private partnerships such as IMI and projects like Mobilise-D are key to fostering innovation and driving the required changes in the field which one company cannot tackle alone.
“Yes, of course, we can measure these things in our own trials,” says Roubenoff, “but how do we convince people that it is meaningful? If we come with a consortium of companies in the pharma industry, academic medical centers and universities that are interested in it, we have a much more powerful platform. This will help us to convince the regulators who approve drugs that this is actually a meaningful and useful endpoint that matters to patients, doctors and regulators alike. And, in the end, that’s what matters to us.”
