AAN report on status of MS drug trials – PART I

A large proportion of the AAN scientific program is centered on therapeutic advances. Whether it’s an early safety study, a phase II or III efficacy trial, an extension phase determining long term effects, or an observational study assessing how a drug is doing in the real world, research on the safety and benefits of treatments is critical knowledge for any conference attendee. We all have one main priority, and that is to improve the health and quality of life for people who are affected by neurological diseases, and so one of the reasons we come together at conferences like AAN is to gain information on the full repertoire of treatments.

For MS, the list of options grows each year. There are currently 10 approved disease-modifying therapies for MS (all indicated for relapsing-remitting MS) in Canada, with a number of others being tested in phase III clinical trials or submitted for Health Canada approval. As measures for treatment safety and efficacy are being discovered and refined, trials for MS drugs ensue and continue to reveal new knowledge about their benefits and risks in humans. Here are some of the first highlights reported at AAN.

Extended dose natalizumab

Natalizumab is an infusion drug and monoclonal antibody that is used to control MS symptoms by blocking entry of harmful immune cells into the central nervous system. The risk of developing progressive multifocal leukoencephalopathy (PML), a rare but potentially fatal brain disease, has been a concern with long term use of natalizumab. Increased susceptibility to PML among people with MS who are taking natalizumab may be due to the blocking activity of the drug, which prevents immune surveillance in the brain. To reduce this blocking activity but maintain the robust efficacy of natalizumab, Dr. Lana Zhovtis-Ryerson from NYU Langone Medical Center and colleagues from 10 U.S. MS centers tested a new dosing regimen.  In the study, they compared health outcomes resulting from the standard dose of 300 mg infusions of natalizumab every 4 weeks to an extended dose of 300 mg every 5-8 weeks. They found that extending the dosing schedule of natalizumab did not affect the drug’s efficacy, with 65% of participants showing no clinical MS activity, and comparable rates of lesions seen on imaging. The new dosing schedule also did not impart any major safety concerns. No cases of PML were reported in the extended dosing group (2 were reported in the standard dose group but this did not reach statistical significance). More work is underway to determine differences in disability progression between the two dosing schedules.

Switching from interferon treatment to teriflunomide

Teriflunomide is a one-daily oral drug which acts by reducing activity of harmful immune cells, thus reducing relapses and delaying accumulation of physical disability. The efficacy and safety of teriflunomide was demonstrated in two pivotal phase III trials, which led to a phase III comparator study that looked at how the drug stacked up against interferon beta-1a. The study – called TENERE – showed no major differences in the efficacy of teriflunomide versus interferon beta-1a. Researchers in Europe conducted an extension phase in which 237 of the participants from TENERE took 14mg of teriflunomide over approximately 2 years, and were observed to determine the long-term effects of the treatment and the effect of switching from interferon treatment to teriflunomide. This was the first study to demonstrate that immediately switching from interferon beta-1a to teriflunomide without a period of being ‘drug-free’ was safe and well-tolerated. Also, there were no significant differences in relapse activity among those who continued to take teriflunomide into the extension phase of the study, and those who initially took interferon beta-1a and switched to teriflunomide in the extension phase.

There are many more treatment updates to come so visit back soon!

One thought on “AAN report on status of MS drug trials – PART I

  1. Meg O'Conor

    Hello Dr. Lee,

    I am connecting to share information with you on dalazatide in development by Kineta for autoimmune diseases.
    • Dalazatide is the first Kv1.3 channel blocker in the clinical pipeline. It’s novel mechanism of action aims to be a “surgical strike” – targeting a subset of immune cells, called effector memory T cells that start the autoimmune response which leads to inflammation and tissue damage.
    • Dalazatide shows potential for an array of autoimmune diseases including – lupus, vasculitis, MS, psoriasis, rheumatoid arthritis, psoriatic arthritis, psoriasis, Crohn’s disease and potentially many other autoimmune diseases.
    • Unlike currently available therapies, dalazatide does not instigate broad immune suppression. This is a genuine difference from other drugs currently available.
    • Kineta has completed two safety studies in healthy volunteers and is about to share top line data on a phase 1B extension study in psoriasis, patients with active disease.
    • Dosing of dalazatide is exceedingly small in quantity, due to the unique potency of this drug. Dalazatide shows very little toxicity and no toxicity to organs in previous human (healthy volunteers) safety studies.
    I hope to share an embargoed news release with top line patient study data in a week or so.
    For more information on dalazatide please take a look at our web site where you will find numerous scientific papers.

    http://www.kinetabio.com/autoimmunediseases.html
    Best regards, Meg O’Conor
    Public Affairs Director
    Kineta

    Reply

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