Advancing MS Knowledge
Early in my career as a neurologist, I could see how terrifying multiple sclerosis (MS) symptoms were for people. Very suddenly, their future became uncertain. Such concerns were particularly acute for those grappling with a new diagnosis.
I remember a young woman, 26, who over the course of a day or two could no longer walk without help. Examining her in the emergency room, we saw a pattern of clinical signs, including muscle weakness and loss of particular sensations on opposite sides of the body. We immediately took an MRI of her spine that revealed a large spot, or demyelinating lesion, on the insulation around the nerve fibers in her spinal cord. Her brain MRI exhibited more lesions — tell-tale signs of MS — in a classic pattern for this disease. I hoped she would recover completely and be able to walk and run normally again. This was her first clinical relapse, also known as an MS attack or exacerbation, and it was a bad one.
At that time, around 2000, MS treatment options were limited. On the other hand, the early treatments that were available gave hope to patients, families, and physicians who had no disease-modifying therapeutic options just ten years earlier. But there was more to do for those battling MS, and I wanted to help.
Developing MS Medicines
I originally joined Genentech about 10 years to develop new medicines for relapsing forms of MS (RMS) and primary progressive MS (PPMS). RMS includes people with relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) with relapses. Over the years, we’ve learned a lot about how to better study MS, with the hope of developing new medicines to help more people living with this disease.
Four Types of MS
is the most common form of MS at diagnosis, in which people experience episodes of acute symptoms followed by recovery periods when outward signs or symptoms do not progress
is a progressive worsening of symptoms after a period of RRMS
is a type of MS that steadily worsens and for which there are still no approved therapies
the rarest type, progressive-relapsing MS is marked by bouts of relapses in between progressive worsening of symptoms
Although the basic approach to testing new medicines for RMS hasn’t changed dramatically, important aspects of clinical trial design and statistics, as well as clinical and imaging assessments have evolved over time. With these adaptations—and the approval of new medicines—we’ve seen improvements in the health of many people with RMS.
In a sense, it’s harder to develop new medicines for RMS today because there are more available treatment options than 10 years ago. For example, until recently, it was standard practice to compare an experimental medicine to a placebo (a dummy drug with no therapeutic effect). Today, more advanced RMS studies are comparing investigational medicines to a commonly prescribed medicine already approved for the treatment of RMS — an “active comparator” — instead of placebo.
In 2013, I gave a talk at the European Medicines Agency (EMA) highlighting some of the complexities involved with both placebo and active comparator approaches to MS study design. Discussion by regulatory agencies and the MS research community on these issues illustrates how far we’ve come in providing better control of RMS; the benchmark for “better” has shifted.
Over the past two decades, clinical studies have also taught us a lot about people living with MS. We’d already learned that the disease varies widely from one person to the next. However, we’ve also learned that brain MRIs often show evidence of MS disease activity even when symptoms are not present. Some people become increasingly disabled relatively rapidly, while others experience very slow disease progression. As we’ve increased the numbers and global reach of patients enrolled in clinical studies, we can better understand how an investigational medicine works across a broad range of people with MS.
Every patient we evaluate increases the richness and power of the data that we gather in clinical studies. Certain aspects of MS, such as disease progression, are challenging to measure and the field continues to innovate in these important areas in clinical trials. We also want to make sure our studies really capture how the disease — and how a potential new medicine — affects different dimensions of a patient’s well-being.
Certain aspects of MS, such as disease progression, are challenging to measure and the field continues to innovate in these important areas in clinical trials.
Treating the Whole Person
The definition of a good outcome for patients with MS has broadened over the past decade, with the emergence of new treatments and a better understanding of the disease. We’re not just interested in how new medicines affect relapses and disease progression. We also want to understand how they suppress more subtle disease activity in the short term, improve overall well-being, and help a person living with MS stay independent longer.
Along with colleagues at Roche, Genentech collaborates in the MS Outcomes Assessments Consortium (MSOAC), which is working to qualify a new measure of disability with regulatory agencies for use in future MS clinical trials. Clinical studies are delving deeper into how MS affects a person’s overall health — physically, mentally, and emotionally — which could tell us whether potential new treatments may improve patients’ lives from the patients themselves.
Meanwhile, we are continually exploring more sensitive and reliable measures of disease activity that may give us a better sense of how well medicines control the disease. Imaging technologies like MRI and ocular coherence tomography (OCT) continue to improve in order to measure aspects of disease activity, such as neurodegeneration, that were challenging to gauge in the past.
These different lines of research will give us a deeper knowledge of the biology of each person’s disease and a more comprehensive understanding of the effects of treatment. Armed with this knowledge, we hope that in the future we will be able to identify patients who are at a higher risk of disease progression and may need more aggressive treatment strategies. We may also be able to better detect when a patient is not responding to a medicine — or when the disease is still active, even though a patient has no obvious symptoms. Ultimately, knowing more about MS and how it responds to treatment in different people will allow doctors to make more informed decisions and help researchers like me develop more medicines for MS.
Ultimately, knowing more about MS and how it responds to treatment in different people will allow doctors to make more informed decisions and help researchers like me develop more medicines for MS.
MS is a lifelong disease that’s usually diagnosed when people are young, so having access to medicines that work in different ways is good for patients. I still remember the young woman who showed up in the ER 15 years ago with difficulty walking and left with a lifelong diagnosis. I hope she has found effective treatments and maintained independence over time. I look forward to bringing patients like her new options and new hope for a better life with MS.