The “2014 Multiple Sclerosis Therapeutic Update,” published in the journal Neurohospitalist by author Bruce Cree, MD, PhD, MCR, provides a positive outlook on the state of current treatments and research for future treatments of multiple sclerosis. A host of new therapies, as well as common-place vitamin D supplementation, are in clinical trials for treating both relapsing and progressive multiple sclerosis.
For relapsing multiple sclerosis, ongoing phase 3 clinical trials involve the agents sphingosine-1-phosphate receptor 1 modulators, daclizumab, ocrelizumab, and laquinimod. Alemtuzumab, a monoclonal antibody like daclizumab and ocrelizumab, passed the challenge of phase 3 testing and is approved in over 30 countries, but not the United States. This provides support for further work that addresses the issue of efficacy if the market size is to be enlarged.
Regarding new administration routes of old treatments, subcutaneous injections of glatiramer acetate may be beneficial if given three times in a week. The phase 3 clinical trial Glatiramer Acetate Low-Frequency Administration (GALA) is ongoing and has so far shown a reduction of relapse rate after one year of treatment. The Food and Drug Administration has approved thrice-weekly glatiramer acetate. Additionally, Efficacy and Safety Study of BIIB017 (ADVANCE) looked at delivery of pegylated interferon beta-1a, a possible improvement over interferon beta-1a. The completed results identified that treatment slowed one-year disability progression.
Unfortunately, progressive multiple sclerosis is less well-served than relapsing multiple sclerosis, but efforts are in place to enhance disease-modifying treatments to slow disability accumulation. FTY720 in Patients With Primary Progressive Multiple Sclerosis (INFORMS), an ongoing but not recruiting phase 3 study from Novartis, has the potential to be the first clinical trial to show efficacy in slowing disability progression in progressive multiple sclerosis. It could also bolster the hypothesis that sphingosine-1-phosphate receptor modulation is a part of protecting neurons.
Other therapies that seek to protect the nervous system include NT-KO-003, an inhibitor of microglial activation from Neurotec Pharma in phase 2 clinical trials for relapsing multiple sclerosis. However, due to its inhibition of a hallmark of progressive multiple sclerosis, MT-KO-003 may also provide benefits for patients with progressive multiple sclerosis.
Remyelination is another neuroprotective strategy, and several agents are being pursued for this purpose. Phenytoin, GSK239512, clemastine, and anti-LINGO are all therapeutics that address remyelination of the central nervous system. Several of these agents may be used as adjuvants to existing therapies that quiet inflammation in the brain.
Far from the final agent investigated for multiple sclerosis, vitamin D is another potential modifier of multiple sclerosis disease progression. Low vitamin D is a risk factor for multiple sclerosis, and a number of studies are administering vitamin D to relapsing patients with hopes of modifying disease. The different trials, if successful, may determine the optimal supplementation level for multiple sclerosis patients.
The majority of these studies are industry-sponsored clinical trials and focus less on anti-inflammatory therapies than studies of previous due to their already successful development and upcoming shift to generics. Instead, treatment options that focus on remyelination and neuronal protection may be the new standards for research.