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As researcher learn more about multiple sclerosis (MS), scientists continue to look for new treatment options. Disease-modifying therapies (DMTs) are medications that can help slow the progression of multiple sclerosis and reduce how often relapses (also called attacks, exacerbations, or flares) occur. On average, developing one new medication to the point of approval takes 10 to 15 years. The FDA has approved more than 20 DMTs to treat multiple sclerosis.
Before the U.S. Food and Drug Administration (FDA) approves a new drug for public use, the drug must first go through a series of studies known as clinical trials. Investigators — doctors and researchers who run clinical trials — must be able to prove through these trials that a new medication is safe and effective compared with therapies that have already been approved.
The FDA’s approval process is designed to ensure that the potential benefits of new drugs outweigh their potential risks, such as side effects.
Before a new drug can be given to humans, investigators first have to show that it’s safe in preclinical studies.
New drugs are first tested in small preclinical studies using lab-grown cells or animals to determine the drug’s toxicity and a safe dose.
Once all preclinical data has been collected, investigators from a pharmaceutical company or research institution submit an investigational new drug (IND) application to the FDA. The FDA reviews the IND application to determine whether the drug can be used in clinical trials.
There are three phases of clinical trials before a drug can be approved, and a fourth, sometimes optional phase after the drug is already in use. Each phase is a step in the process of proving whether the drug is safe and effective, with as little risk as possible to participants in the clinical trials.
Once the FDA determines the drug is safe to test on humans, investigators can begin clinical trials. There are three phases of clinical trials used to look at different aspects of a medication, including dosing, side effects, and efficacy (whether it produces the intended result).
In early clinical trial phases, investigators are interested in learning about the drug’s safety and potential side effects. Although preclinical studies can help give a good idea of dosing, investigators won’t know exactly how a drug works until it’s given to humans.
Traditionally, phase 1 studies consist of 20 to 80 healthy volunteers. During a phase 1 study, participants are given the drug being tested at different doses to make sure it’s safe, track side effects, and study how it’s absorbed by the body.
According to the FDA, only 70 percent of drugs move into phase 2 clinical trials.
Once phase 1 trials show that a drug is safe to use, phase 2 clinical trials focus on studying its effectiveness. In phase 2 trials, the new drug being studied is often compared with a different treatment or a placebo (an inactive substance).
These studies can range in size from a few dozen to a few hundred people. Depending on the form or forms of MS being targeted in the trial, researchers may select volunteers with primary progressive MS (PPMS) or relapsing forms of MS — relapsing-remitting MS (RRMS), clinically isolated syndrome (CIS), and active secondary progressive MS (SPMS).
Because these studies have more volunteers, they help investigators find less common side effects that may not have been seen in phase 1. Only 33 percent of drugs that reach this stage move to phase 3 clinical trials.
The final and largest of the clinical trial phases is phase 3, which is used to determine whether a drug is effective in treating a disease or condition. These studies recruit hundreds to thousands of volunteers to take either a new drug or a currently available therapy for comparison. Phase 3 studies also give investigators more information about a drug’s safety and the side effects that participants experience.
New medications must meet certain outcomes or treatment goals that measure their effectiveness. These outcomes are set before a clinical trial begins to ensure the study goals and standards are the same throughout the trial.
Once investigators have completed their trials, they compile all data from preclinical and clinical studies to submit a new drug application (NDA) for FDA approval. A team of doctors, scientists, and other neurology specialists at the FDA reviews the NDA to determine whether a new drug is safe and effective.
Read about the most effective medications for MS.
The review team considers the results of the clinical trials, particularly how effective the new drug is compared with currently available therapies. They also carefully consider the outcomes and the participants’ experiences to weigh the risks and benefits of the new medication.
At this stage, the FDA may still deny a new medication if participants can’t tolerate it, if it proves ineffective, or if it has dangerous side effects. Once all data has been reviewed, a senior FDA official makes the final decision to approve the new MS treatment.
After a drug has been FDA-approved, the FDA can request a phase 4 study (postmarketing study) to look at side effects that might have been missed in phase 1, 2, and 3 trials.
After phase 3 clinical trials, a drug can be approved. Once a drug is approved and being used, a phase 4 clinical trial can continue to study it, searching for ways to improve effectiveness or make other helpful changes.
DMT clinical trials specifically measure disease progression, disability progression, and relapse rates.
MS is a progressive disease. Over time, damage to the central nervous system (CNS) and symptoms get worse, requiring more advanced treatment. Disease progression in MS is measured by the formation of new lesions (areas of damage) or the worsening of lesions a person already has on the myelin of their brain and spinal cord.
Doctors use MRI scans to visualize these lesions. At the beginning of a clinical trial, participants have MRI scans taken to establish a baseline (starting point) to compare to later scans. Throughout the study, they’ll continue to have scans to monitor any changes. Slowing down disease progression can help people with MS stay active and reduce the ways the disease impacts everyday life.
Disability in MS is typically measured using the Expanded Disability Status Scale (EDSS). This scale uses numbers 0 through 10 to quantify disability as a combination of muscle, speech, vision, and memory problems.
At the beginning of an MS clinical trial, participants have their EDSS score measured to establish a baseline. At the three- and six-month points of the study, a neurologist will measure their EDSS score again to see if and how much their MS has progressed. The goal of new DMT medications is to slow disability progression more than currently approved therapies.
MS is a disease with periods of flares and remissions when MS symptoms worsen and improve. In DMT clinical trials, investigators track how often participants experience relapses as a way to measure disease activity and progression. Remission is the period after a relapse when MS symptoms either partially or fully disappear.
The annualized relapse rate is the average number of MS relapses a group of participants has during one year. The goal of new DMTs is to reduce this number compared with currently available therapies.
Doctors may also treat MS with medications approved by the FDA for other conditions — a practice known as off-label use."
For example, rituximab was approved for cancer use, but it’s now often used to treat MS, since research has shown that it can reduce relapses and limit MS disease progression. Off-label use can be beneficial because once a drug has been proven to be safe and has shown good results for MS, doctors can begin using it right away, while the lengthier process to get MS added to its FDA-approved uses carries on.
MyMSTeam is the social network for people with multiple sclerosis and their loved ones. On MyMSTeam, members come together to ask questions, give advice, and share their stories with others who understand life with MS.
Have you considered participating in a clinical trial for a new MS medication? Why or why not? Share your thoughts in the comments below, or start a conversation on your Activities page.
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I love animals too but I imagine sometimes they need to be used to help humans. I read an article not too long ago how some MS patients may genetically not progress over time- a different form of MS… read more
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